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

CYSTITIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P...

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CYSTITIS 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 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Cystitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83873-9 1. Cystitis-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 cystitis. 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 CYSTITIS .................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Cystitis........................................................................................ 35 E-Journals: PubMed Central ....................................................................................................... 92 The National Library of Medicine: PubMed ................................................................................ 95 CHAPTER 2. NUTRITION AND CYSTITIS ........................................................................................ 139 Overview.................................................................................................................................... 139 Finding Nutrition Studies on Cystitis....................................................................................... 139 Federal Resources on Nutrition ................................................................................................. 144 Additional Web Resources ......................................................................................................... 144 CHAPTER 3. ALTERNATIVE MEDICINE AND CYSTITIS .................................................................. 147 Overview.................................................................................................................................... 147 National Center for Complementary and Alternative Medicine................................................ 147 Additional Web Resources ......................................................................................................... 155 General References ..................................................................................................................... 164 CHAPTER 4. CLINICAL TRIALS AND CYSTITIS ............................................................................... 165 Overview.................................................................................................................................... 165 Recent Trials on Cystitis............................................................................................................ 165 Keeping Current on Clinical Trials ........................................................................................... 167 CHAPTER 5. PATENTS ON CYSTITIS ............................................................................................... 169 Overview.................................................................................................................................... 169 Patents on Cystitis..................................................................................................................... 169 Patent Applications on Cystitis ................................................................................................. 191 Keeping Current ........................................................................................................................ 204 CHAPTER 6. BOOKS ON CYSTITIS .................................................................................................. 205 Overview.................................................................................................................................... 205 Book Summaries: Federal Agencies............................................................................................ 205 Book Summaries: Online Booksellers......................................................................................... 207 The National Library of Medicine Book Index ........................................................................... 209 Chapters on Cystitis................................................................................................................... 210 Directories.................................................................................................................................. 215 CHAPTER 7. MULTIMEDIA ON CYSTITIS ........................................................................................ 217 Overview.................................................................................................................................... 217 Video Recordings ....................................................................................................................... 217 Bibliography: Multimedia on Cystitis ....................................................................................... 219 CHAPTER 8. PERIODICALS AND NEWS ON CYSTITIS ..................................................................... 221 Overview.................................................................................................................................... 221 News Services and Press Releases.............................................................................................. 221 Newsletter Articles .................................................................................................................... 223 Academic Periodicals covering Cystitis ..................................................................................... 225 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 227 Overview.................................................................................................................................... 227 U.S. Pharmacopeia..................................................................................................................... 227 Commercial Databases ............................................................................................................... 229 Researching Orphan Drugs ....................................................................................................... 230 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 235 Overview.................................................................................................................................... 235 NIH Guidelines.......................................................................................................................... 235 NIH Databases........................................................................................................................... 237

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Other Commercial Databases..................................................................................................... 240 APPENDIX B. PATIENT RESOURCES ............................................................................................... 241 Overview.................................................................................................................................... 241 Patient Guideline Sources.......................................................................................................... 241 Associations and Cystitis........................................................................................................... 259 Finding Associations.................................................................................................................. 260 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 263 Overview.................................................................................................................................... 263 Preparation................................................................................................................................. 263 Finding a Local Medical Library................................................................................................ 263 Medical Libraries in the U.S. and Canada ................................................................................. 263 ONLINE GLOSSARIES................................................................................................................ 269 Online Dictionary Directories ................................................................................................... 272 CYSTITIS DICTIONARY............................................................................................................. 273 INDEX .............................................................................................................................................. 363

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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 cystitis is indexed in search engines, such as www.google.com or others, a nonsystematic 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 cystitis, 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 cystitis, 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 cystitis. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to cystitis, 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 cystitis. The Editors

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

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

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

Adolescent Urinary Tract Infections Source: Adolescent Medicine: State of the Art Reviews (STARS). 11(2): 293-313. June 2000. Contact: Available from Hanley and Belfus, Inc. Medical Publishers, Philadelphia 210 South 13th Street, Philadelphia, PA 19107. (215) 546-7293 or (215) 546-4995. (800) 9621892. Fax: (215) 790-9330. Website: www.hanleyandbelfus.com. Summary: Acute cystitis (bladder infection) is one of the most common non-skin related conditions in sexually active adolescent girls. This article reviews adolescent urinary tract infections (UTIs). The authors note that a close relationship between UTI and sexual activity and, therefore, with sexually transmitted diseases (STDs) gives the condition heightened importance and urgency. UTIs in adolescence indicate the need for

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an STD evaluation and counseling for sexual activity. In most cases, the diagnosis of UTI in an adolescent is straightforward and classified as upper tract, lower tract, or both, based on symptoms. The exact incidence of UTIs in adolescence probably varies with other risk factors; the prevalence is 1 percent for girls and much less for boys. The authors discuss pathogenesis, pathology, clinical manifestations, differential diagnosis, laboratory tests (pyuria, quantitative urinalysis), etiology, virulence factors, treatment, prevention, and prognosis. A final section addresses special considerations, including asymptomatic bacteriuria, spina bifida, neurogenic bladder, vesicoureteral reflux and reflux nephropathy, kidney transplant, diabetes mellitus, fungal UTIs, viral UTIs, renal or perinephric abscess, recurrent infections, lower urinary tract anomalies, urolithiasis (urinary stones), catheter related infections, rheumatoid arthritis and Proteus mirabilis bacteriuria, and pregnancy. The authors note that overlap of urethral and gynecologic symptoms emphasizes the coexistence of STDs with UTIs. Problems with diagnosis may occur because the history may not be forthcoming and STDs may be asymptomatic. The authors encourage physicians to maintain a high index of suspicion for UTIs and STDs in any adolescent with urinary symptoms. 7 figures. 6 tables. 56 references. •

Comparison of Cystoscopic and Histological Findings in Patients with Suspected Interstitial Cystitis Source: Journal of Urology. 164(6): 1908-1911. December 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: Although the exact etiology (cause) of interstitial cystitis (IC) remains elusive, bladder inflammation appears to be common in many patients. The National Institutes of Health (NIH) have established diagnostic criteria for IC based on the presence of irritative voiding symptoms in the absence of other identifiable pathology. This article reports on a study undertaken to determine whether the severity of cystoscopic findings correlated with histological evidence of inflammation in 69 patients with suspected interstitial cystitis. The patients all underwent cystoscopy, hydrodistention, and bladder biopsy under anesthesia. The cystoscopic examination revealed no evidence of IC in 6 patients (9 percent), mild changes in 27 patients (39 percent), moderate changes in 23 patients (33 percent), and severe changes in 13 patients (19 percent). Histological examination revealed no inflammation in 21 patients (30 percent), mild inflammation in 28 patients (41 percent), moderate inflammation in 11 patients (16 percent), and severe inflammation in 9 patients (13 percent). Histological scores correlated poorly with total and scaled cystoscopic severity scores. The authors conclude that the severity of cystoscopic findings observed during hydrodistention with anesthesia does not appear to correlate with the degree of inflammation identified histologically in patients with suspected IC. In addition, during analysis, the authors anecdotally noted more severe findings in older patients. An appendix to the article lists the NIH criteria. 2 tables. 22 references.

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Incidence of Helicobacter Pylori in Patients with Interstitial Cystitis Source: European Urology. 40(6): 652-654. December 2001. Contact: Available from S. Karger Publishers, Inc. 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. Summary: Chronic gastritis (stomach inflammation) has compelling similarities to interstitial cystitis (IC, a painful, inflammatory condition of the bladder). Both are characterized by chronic pain in a tubular organ. Histologically, epithelial (lining)

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damage, inflammatory response in the lamina propria, and epithelial ulcerations are seen. An infective cause was rarely considered until the emergence of Helicobacter pylori over the past 15 years. This article reports on a prospective, controlled study of 15 patients who had urinary symptoms fulfilling the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) criteria for IC. All patients underwent cystoscopy under general anesthesia at which the macroscopic appearance of the bladder was noted and biopsies were taken. The biopsy material underwent histological examination and CLO (Campylobacter pylori-like organism) test. Control patients who were undergoing cystoscopy for reasons other than investigation of IC also had biopsy taken and the CLO test was performed on these specimens. Five of the 15 patients with symptoms and signs of IC had a positive CLO test. Three of 15 patients of the control group had a positive CLO test. There was no statistical difference between the 2 groups. The authors conclude that their small prospective control study does not support the hypothesis that H. pylori is an important component in the pathogenesis (development) of IC. 1 table. 17 references. •

Nonbladder Related Symptoms in Patients with Interstitial Cystitis Source: Journal of Urology. 166(2): 557-562. 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: Clinical experience and epidemiological studies suggest that patients with interstitial cystitis (IC) have multiple nonbladder related symptoms. This article reports on a study undertaken to test this hypothesis. The authors used the University of Wisconsin scale to compare the scores for patients with IC to those for control subjects. This validated questionnaire includes 7 bladder and 18 reference symptoms not related to the bladder. The study included a total of 35 female patients with IC and 35 age matched female controls. For the 7 bladder symptoms, the difference between IC and control groups was extremely significant. Patients with IC had higher scores than controls for 9 reference symptoms, including other pelvic discomfort, backache, dizziness, chest pain, aches in joints, abdominal cramps, nausea, heart pounding, and headache. However, they did not have higher scores for blind spots or blurred vision, numbness or tingling in fingers or toes, swollen ankles, feeling of suffocation, sore throat, cough, flu, nasal congestion, and ringing in ears (tinnitus). The majority of patients with IC had a 0 score for all but 2 of the reference symptoms (backache and aches in joints). Patients with IC had increased scores for 9 reference symptoms, but did not indiscriminately report high scores for generalized complaints. This result suggests that in some cases of IC, the pathophysiology may affect other organ systems besides the bladder. Alternatively, some of these symptoms may result from changes in sleep pattern or other factors associated with IC. An editorial commentary is appended to the article. 5 tables. 16 references.

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Increasing Antimicrobial Resistance and the Management of Uncomplicated Community-Acquired Urinary Tract Infections Source: Annals of Internal Medicine. 135(1): 41-50. July 3, 2001. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org.

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Summary: Community acquired urinary tract infections (UTI) are among the most common bacterial infections in women. Therapy for these infections is usually begun before results of microbiological tests are known. Furthermore, in women with acute uncomplicated cystitis, empirical therapy without a pretherapy urine culture is often used. The rationale for this approach is based on the highly predictable spectrum of etiologic agents causing UTI and their antimicrobial resistance patterns. However, antimicrobial resistance among uropathogens causing community-acquired UTIs, both cystitis and pyelonephritis, is increasing. This article reports on this increase and ponders the management of UTIs in light of this evidence. The authors note that most important is the increasing resistance of the uropathogens to trimethoprimsulfamethoxazole (TMP-SMX), the current drug of choice for treatment of acute uncomplicated cystitis in women. The authors stress that in the outpatient setting, identifying risk factors for TMP-SMX resistance and knowing the prevalence of TMPSMX resistance in the local community are important steps in choosing an appropriate therapeutic agent. When choosing a treatment regimen, physicians should consider such factors as in vitro susceptibility, adverse effects, cost-effectiveness, and selection of resistant strains. Using a management strategy that takes these variables into account is essential for maintaining the safety and efficacy of treatment for acute UTI. A patient care algorithm is included. 1 figure. 4 tables. 44 references. •

What Do We Know About the Urinary Tract Infection-Prone Individual? Source: Journal of Infectious Diseases. 183(Supplement 1): S66-S69. March 1, 2001. Contact: Available from Journal of Infectious Diseases. University of Chicago Press, Journals Division, P.O. Box 37005, Chicago, IL 60637. (773) 753-3347. Fax (773) 753-0811. E-mail: [email protected]. Website: www.journals.uchicago.edu. Summary: Host factors play an important role in the balance between sterility and infection of the urinary tract. This article discusses current knowledge about individuals who are prone to urinary tract infection (UTI). Host defenses typically include unobstructed flow of urine (to wash out bacteria from the lower urinary tract), the antibacterial effect of urine, glycoproteins that block adherence of bacteria to the urothelial and vaginal mucosa, and immunological responses that facilitate bacterial clearance. Complicated UTIs are associated with anatomic, functional, or metabolic abnormalities of the urinary tract that disable the natural defenses and lead to significant destruction of renal tissue. Uncomplicated infections are associated with more subtle, variable alterations governed by genetic, biologic, and behavioral or environmental factors that promote bacterial access to and colonization or infection of the urinary tract. The author notes that the UTI prone individual is actually free of infection most of the time, presumably due to the innate defense mechanisms of the urinary tract. Nevertheless, transient or permanent breaches in the host defense allow bacterial access to and infection of the urinary tract. The frequency and severity of the episodic lapses in defense determine the type and extent of infection. Minor weaknesses in host defense allow only virulent (very strong) pathogens to cause simple cystitis (bladder infection), which will clear spontaneously or with minimal antimicrobial therapy. More severe host deficiencies are subject to invasion by less virulent strains, lead to more severe infections, and require more precise and extensive therapy. The variety of host defense and susceptibility factors frequently merge and fluctuate within a given individual, making the study, diagnosis, and management of UTIs a difficult and rewarding endeavor.

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Interstitial Cystitis: Current Issues and Controversies in Diagnosis Source: Urology. 57(6 Supplement 1): 82-88. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: In this article, current tests for the diagnosis of interstitial cystitis (IC) are reviewed, including clinical assessment, urodynamic testing, cystoscopy, bladder biopsy, and urinary markers. The authors performed a MEDLINE search of all studies dealing with the diagnosis of IC. These studies were critically reviewed with the goal of arriving at a utilitarian approach to IC diagnosis. IC is being diagnosed with increasing frequency. However, the diagnostic criteria are nonuniform and there is significant overlap between chronic pelvic pain sydnromes in men and women and IC. Diagnosis of IC can be made clinically (based on symptoms, history, and examination) and by cystoscopy and hydrodistention of the bladder. The sensitivity and specificity of urinary markers have not been prospectively studied. Individual practitioners continue to use the various diagnostic tests. The authors conclude that there is a clear need for uniform diagnostic criteria for clinical diagnosis as well as epidemiologic and research studies. 4 tables. 40 references.

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Interstitial Cystitis: An Overlooked Cause of Pelvic Pain Source: Postgraduate Medicine. 88(1): 101-109. Summary: In this article, the author discusses the manifestations of interstitial cystitis, appropriate diagnostic methods, and available treatment options. Interstitial cystitis is a disease primarily affecting young and middle-aged women which is characterized by pelvic pain, urinary frequency, and dyspareunia. Of the available treatments, the most common are intermittent hydrodilation of the bladder and intermittent intravesical instillation of dimethyl sulfoxide. The author stresses that although interstitial cystitis is uncommon, its potentially devastating effects may be modified or even averted if primary care physicians are familiar with its presentation and maintain a high index of suspicion. 2 figures. 2 talbes. 16 references. (AA-M).

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Self-Care Regimens for Patients With Interstitial Cystitis Source: Urologic Clinics of North America. 21(1): 121-130. February 1994. Contact: Available from W.B. Saunders Company. The Curtis Center, Independence Square West, Philadelphia, PA 19106. (800) 654-2452. Summary: In this article, the author explores self-care regimens for patients with interstitial cystitis (IC). The author notes that coping with interstitial cystitis requires dealing with chronic pain and sleep deprivation, acceptance of a difficult diagnostic process, and patience during a trial-and-error regimen to find the combination of therapeutic modalities that can achieve a remission in symptoms. Topics covered include the systemic manifestations of IC; gynecologic manifestations of IC; the typical flare and remission course of IC; etiology; diagnostic work-up; recommended approach to patient management; and self-care treatment regimens, including dietary manipulation, nutritional supplements, stress reduction, exercise, bladder retraining, and bladder instillations; and dealing with chronic pain. 2 figures. 5 tables. 51 references.

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Reframing Women's Health: Tension and Paradox in Framing Interstitial Cystitis Source: Journal of Women's Health. 2(1): 81-84. Spring 1993. Contact: Available from Mary Ann Liebert, Inc., Publishers. 1651 Third Avenue, New York, NY 10128-3629. (212) 289-2300. Summary: In this article, the author presents a framework for considering interstitial cystitis (IC), a relatively rare but probably underdiagnosed condition that affects 10 times more women than men. The author briefly describes IC and its relationship to assumptions about chronic pain, female pelvic pain, and somatization disorder. Topics covered include issues of diagnosis and treatment, and theories of chronic pain. The implications of either ignoring or assuming psychologic factors in the development of IC are explored to illustrate the tension and paradox inherent in adopting holistic models for women's health. 31 references. (AA-M).

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Interstitial Cystitis: A Patient's Perspective Source: Urologic Clinics of North America. 21(1): 1-5. February 1994. Contact: Available from W.B. Saunders Company. The Curtis Center, Independence Square West, Philadelphia, PA 19106. (800) 654-2452. Summary: In this article, the authors discuss interstitial cystitis (IC) from the patient's perspective. After reprinting a number of first-hand accounts from patients who struggled for years with undiagnosed IC, the authors discuss the possible prevalence of IC; the symptoms; the difficulties in obtaining an accurate diagnosis; epidemiological studies that gathered and analyzed information about IC; the role of the physician; educating physicians about IC; and the role of the Interstitial Cystitis Association (ICA). The authors convey to the reader a sense of the struggles that the patient with IC must face. 7 references.

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Changing Concepts in Interstitial Cystitis (editorial) Source: Journal of Urology. 158(3): 794. September 1997. Summary: In this brief editorial, the author reviews the changes in the understanding and treatment of interstitial cystitis (IC) that have occurred in the past decade. Severity of the disease can be measured in terms of the intensity and duration of symptoms. Breakthroughs have allowed earlier recognition of the disease. Patients who start therapy early are more likely to benefit than are patients who have had the disease longer. The author explores various theories of pathogenesis of IC, noting that the most widely held belief is that epithelial dysfunction causes permeability and diffusion of small solute, primarily potassium, which may trigger sensory nerves and injure tissue and actually help accelerate the disease process. Diagnosis focuses on one or more symptoms of urgency, frequency, and pain persisting in the presence of negative cultures, normal cytology, no hematuria, and no other definable cause. The author also outlines present therapeutic approaches, including dimethylsulfoxide treatments, hydroxyzine, intravesical heparin, and oral pentosanpolysulfate. The editorial also serves as an introduction to a report in the same issue that describes the use of Larginine for patients with IC. 4 references. (AA-M).

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Antimicrobial Therapy for Urinary Tract Infections Source: Seminars in Nephrology. 14(6): 551-569. November 1994.

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Contact: Available from W.B. Saunders Company, Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: In this review article, the authors present an overview of antimicrobial therapies for commonly seen urinary tract infections (UTI's). Topics include the rationale for therapy; bacterial resistance; acute uncomplicated cystitis in women; unresolved UTI's; recurrent UTI's in women; acute uncomplicated pyelonephritis in women; complicated UTI's; asymptomatic bacteriuria and UTI in pregnancy; acute bacterial prostatitis; fungal infections; chronic bacterial prostatitis; indwelling catheter-related infections; and asymptomatic bacteriuria. The authors stress that, in order to optimize treatment with antimicrobial agents, the physician must categorize patients into groups of disease processes. They also remind readers that not all patients with bacteriuria need to be treated, particularly in light of the fact that the indiscriminate and excessive use of antimicrobials can lead to resistance. 1 figure. 5 tables. 105 references. •

Percutaneous Sacral Nerve Root Neuromodulation for Intractable Interstitial Cystitis Source: Journal of Urology. 165(6): 884-886. March 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. Summary: In this study, the authors evaluated the effectiveness of percutaneous sacral nerve root neuromodulation in women with refractory (resistant to treatment) interstitial cystitis (IC, an irritative bladder lining disease). The authors prospectively evaluated 15 consecutive women (mean age 62 years) who had refractory IC, to determine the efficacy of percutaneous (through the skin) stimulation of the S3 sacral roots. All women fulfilled the criteria for the diagnosis of IC and were unresponsive to standard oral or intravesical (in the bladder) therapy. The response to the present treatment was assessed using pain scores, urinary diary variables, and quality of life surveys. Mean voided volume during treatment increased from 90 to 143 ml. Mean daytime frequency and nocturia (urinating at night) decreased from 20 to 11 and 6 to 2 times, respectively. Mean bladder pain decreased from 8.9 to 2.4 points on a scale of 0 to 10. In addition, the quality of life parameters of social functioning, bodily pain, and general health significantly improved during the stimulation period. Of the women in the study, 73 percent requested to proceed to complete sacral nerve root implantation. The authors conclude that women with intractable IC respond favorably to percutaneous sacral stimulation. Permanent sacral implantation may be an effective treatment modality in this population, but further long term investigation is warranted. 2 tables. 20 references.

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Interstitial Cystitis: A Chronic Visceral Pain Syndrome Source: Urology. 57(6A Supplement): 32-39. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: Interstitial cystitis (IC) has remained an unresolved problem in clinical urology. The etiology (cause) and pathophysiology (how it develops) of IC are still undetermined, and to date the diagnosis is based on the clinical characteristics of the disease and the exclusion of other diseases and pathology that can mimic the symptoms of IC. In this review article, the author proposes an approach to IC that takes into account the observation that IC shares many features with other chronic nonmalignant visceral pain syndromes. This approach is based on the conceptualization of 3

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hypotheses: a spectrum of different insults can lead to chronic visceral pain in patients with IC; different underlying pathogenic pain mechanisms may require different pain treatment strategies for patients diagnosed with IC; and multiple different pathogenic pain mechanisms may coexist in the same patient requiring several different pain treatment strategies (perhaps at the same time) to successfully treat chronic visceral pain associated with IC. This concept is likely to lead to new insights into the pathophysiologic mechanisms of IC and to novel treatment avenues for patients with IC and also for patients with other chronic visceral pain syndromes. 1 figure. 53 references. •

Toward a Precise Definition of Interstitial Cystitis: Further Evidence of Differences in Classic and Nonulcer Disease Source: Journal of Urology. 167(6): 2470-2472. June 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: Interstitial cystitis (IC) is a bothersome condition in urological practice. There is continuous discussion on the extent and demarcation of this syndrome. Accumulated evidence indicates that IC is a heterogeneous syndrome. Today it is often divided into classic and nonulcer disease. Compared with classic IC, the nonulcer type appears different in terms of demographic, endoscopic, and histological findings as well as in the response to various types of treatment. However, in clinical series subdivision is not always performed, which makes it difficult to draw conclusions. This article reports on a study undertaken to determine whether there are additional dissimilarities in clinical presentation in the 2 subtypes of IC. The authors evaluated 130 patients with classic and 101 with nonulcer IC, diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) criteria by surveying the patients' clinical records, including voiding diaries. Patients with nonulcer disease were younger at diagnosis and at symptom onset. Furthermore, there was a marked and significant difference in bladder capacity while patients were under general anesthesia. The authors conclude that these findings together with previous findings clearly demonstrate that the 2 subtypes of IC represent separate entities. The authors suggest refining the NIDDK criteria, so that subtyping scientific materials is considered mandatory, thus ensuring that the 2 subtypes are evaluated separately in clinical studies. 2 figures. 36 references.

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Prevalence of Symptoms Related to Interstitial Cystitis in Women: A Population Based Study in Finland Source: Journal of Urology. 168(7): 139-143. 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: Interstitial cystitis (IC) is a chronic inflammatory bladder disease. Despite intensive research, its prevalence, etiology (cause), diagnosis, and appropriate treatment remain elusive. In this article, the authors estimated the prevalence of urinary symptoms related to IC in women in Finland. The authors randomly selected 2,000 study participants 18 to 71 years old from the Finnish population register. The prevalence of urinary symptoms was evaluated by mailed questionnaire. Women with high symptoms and problem scores, including nocturia (getting up at night to urinate) and excluding urinary infection and pregnancy, were considered most likely to have IC. The response rate after 2 mailings was 67.2 percent (1,343 respondents). After further exclusions, 1,331 women (66.6 percent) comprised the final study group. Of these respondents, 11 (0.8 percent) reported severe symptoms and problems, including 6

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women who fulfilled the criteria for probably IC. The authors conclude that the prevalence of urinary symptoms corresponding to probable IC is 450 per 100,000, which is an order of magnitude higher than previously reported. 3 tables. 21 references. •

Surgical Treatment of Interstitial Cystitis in Women Source: International Urogynecology Journal. 11(2): 113-119. 2000. Contact: Available from Springer-Verlag New York Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Fax (212) 473-6272. Summary: Interstitial cystitis (IC) is a clinical entity that has been known for a century, but its pathophysiology remains largely unknown, and the optimal treatment is a matter of ongoing discussion. This article reviews the literature on the current surgical treatment of IC. The authors emphasize that a successful strategy for treatment relies on precise appraisal of symptoms, clinical findings and histology, as well as on the patient's individual personality. The least invasive treatment possible should be chosen, and only after conservative options have been exhausted should a surgical solution be considered. In this respect, anatomical bladder capacity plays an important role. A large bladder capacity indicates the potential for conservative treatment and may be regarded as a negative predictor for the outcome of orthotopic bladder substitution. In contrast, a small anatomical bladder capacity is unlikely to respond to conservative therapy but is associated with a high probability of successful orthotopic bladder substitution (bladder resection and then augmentation, usually with a segment of bowel). Alternative procedures are ureterocolic implantation and continent urinary diversion. Incontinent urinary diversion as a primary choice seems to be outdated. 2 tables. 70 references.

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Treating Interstitial Cystitis Safely Source: Patient Care. 33(4): 32-35, 39-40, 43-44. February 28, 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: Interstitial cystitis (IC) is a condition characterized by urinary frequency, urgency, and often excruciating pain. The condition can be chronic, with periods of symptomatic flare up and remission. This article reviews the epidemiology and demographics of IC, then focuses on the treatment options that can be successful. The author stresses that, despite the chronic nature of IC and its enigmatic etiology, IC can be treated safely and symptoms eased. Chief among the therapies are hydrodistention of the bladder and intravesical therapy with dimethyl sulfoxide. An oral drug called pentosan polysulfate (Elmiron) is now available for a noninvasive approach. The author reviews the diagnosis of IC, noting that an accurate diagnosis requires a complete patient history, followed by cystoscopy under anesthesia and bladder hydrodistension. Bladder biopsy is useful but not essential. Severe IC can be associated with Hunner's ulcers and reduced bladder capacity. A careful pelvic examination is needed to rule out vaginitis, vulvar lesions, and urethral diverticula. One sidebar details current hypotheses regarding the etiology (causes) of IC. 2 figures. 3 tables. 28 references.

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Sex and Interstitial Cystitis: Explaining the Pain and Planning Self-Care Source: Urologic Nursing. 13(1): 4-11. March 1993. Summary: Interstitial cystitis (IC) is a disease that can disrupt many aspects of a person's life, with increased urinary frequency and urgency, along with intermittent or constant pain. This article addresses the phenomenon of added pain with sexual activity in

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people with IC. Topics include dyspareunia, other sexual problems, medications and their possible effects on sexual response, the phases of female sexual response, and identifying the problems and finding solutions. The author focuses on the importance of self-care in dealing with the chronic nature of IC. 1 figure. 11 tables. 31 references. •

Modified Urodynamics for Interstitial Cystitis Source: Techniques in Urology. 3(2): 65-68. Summer 1997. Summary: Interstitial cystitis (IC) is a poorly understood syndrome. Patients who present with pelvic pain, urgency, frequency, dysuria, or any combination of these symptoms may pose a diagnostic dilemma. They may have bladder related symptoms or nonbladder related symptoms. This article reports on a study that outlined a modified urodynamics test to discriminate between bladder related and nonbladder related patients. Consecutive IC patients and stress incontinent controls underwent modified urodynamics. Testing consisted of an epithelial leak test, a filling cystometrogram, bladder emptying and instilling lidocaine intravesically, and repeat cystometrogram after bladder emptying. The authors conclude that the epithelial leak test and lidocaine test predict reliably if a patient has bladder related or nonbladder related symptoms. Modified urodynamics permits a logical stratification of IC patients and may predict treatment response. The data show that the combination of tests identifies patients with sensory urgency. This information is useful as some of these patients may be managed with intravesical anesthetics such as marcaine. The data suggest that an IC patient with a negative epithelial leak test and negative lidocaine test may not need anesthetic hydrodistension for diagnosis unless bladder carcinoma in situ is suspected. These patients are also likely not to benefit from bladder-specific therapies currently available and thus are often difficult to manage. An IC patient with positive leak and lidocaine tests will usually have glomerulations and low anesthetic capacity. In this group, a presumptive diagnosis may be considered and glycosamino-glycantargeted modalities may be considered, with or without the option of anesthetic hydrodistension. 3 figures. 8 references. (AA-M).

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Diagnosis and Treatment of Interstitial Cystitis Source: Urologic Nursing. 20(2): 101-107, 131. April 2000. 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: Interstitial cystitis (IC) is a severe bladder disease of unknown etiology with no cure. The diagnosis and treatment of this difficult disease has frustrated both patients and clinicians alike. This article reviews the signs and symptoms of IC, discusses treatment modalities and their effects, and offers suggestions for nurses who wish to respond to patient experiences effectively. Multimodality treatment is recommended and can include dietary modification, fluid management, physical therapy, oral pharmacotherapy (medicines), intravesical (instilled into the bladder) agents, pain management, and surgery. Fluid management is a key feature of therapy for IC. Increasing fluid intake may markedly improve IC symptoms as less concentrated urine may be less irritating to the bladder lining. Patient education is extremely important. The authors stress that patients must understand that IC is a chronic disease and it may take time to find the best treatment combination to alleviate their symptoms. The patient must be involved in determining the treatment course and a team approach using nursing staff, physical therapists, rheumatologists, pain clinics, and others is often beneficial. 4 tables. 35 references.

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Interstitial Cystitis: Update on Etiologies and Therapeutic Options Source: Journal of Women's Health and Gender-Based Medicine. 8(6): 745-758. 1999. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $7.00 plus shipping and handling. Summary: Interstitial cystitis (IC) is a syndrome of pelvic or perineal pain, urinary urgency, and frequency. IC is now defined as a multifactorial syndrome, not a single condition. A variety of etiologies (causes) for IC have been proposed, but none has been definitely proven. Since the etiologies for IC remain unknown, the current treatments are empiric. This article reviews the major theories of etiology for IC and discusses the current treatment options with relevance to each proposed etiology. Treatments discussed include dietary changes, bladder timing, bladder distention, drug treatments (Elmiron, heparin, hyaluronic acid), DMSO distillation, amitriptyline, calcium channel blockers, immunosuppressive agents, antibiotics, treatments for pain, and surgery. The author concludes that no single treatment is effective for all IC patients. Therefore, the approach is to try different treatments, alone or in combination, until symptom relief is satisfactory. In some cases, none of the empiric IC treatments are successful. These patients require adjunctive pain management, and a small minority of IC patients resort to surgery if all other options fail. The article includes two patient care algorithms. 2 figures. 111 references.

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Current Controversies that Adversely Affect Interstitial Cystitis Patients Source: Urology. 57(6 Supplement 1): 89-94. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: Interstitial cystitis (IC) remains a diagnosis of exclusion, based on the symptoms of urinary urgency, frequency, and pelvic pain in the absence of other definable causes. This article reviews certain areas of controversy in the field of IC research that have a significant adverse effect on patients. Many physicians still do not believe that IC exists, or else believe that it is a rare postmenopausal condition. This can cause significant delays in diagnosis and treatment. IC is particularly problematic in children, whose symptoms are often diagnosed as 'voiding dysfunction' and are thought to be self-limiting. IC can also be problematic for men, who are often unsuccessfully treated for prostatitis (infection of the prostate) over the course of many years, and for whom the diagnosis of IC is never considered. In some cases, when no diagnosis is made, patients are left to live with severe, debilitating symptoms and have nowhere to turn for help. Resistance to treating severe nonmalignant pain with opioid medication further compounds this problem and has led to suicide in this patient population. The 'gold standard' of cystoscopy with hydrodistention is now being questioned, and an overreliance on the potassium test, which has a high false negative rate, may lead to significant underdiagnosis of IC. New urinary markers hold promise for both diagnostic as well as therapeutic potential, but are not yet commercially available. IC may be an organ specific disease in some patients and a systemic condition in others. Many patients have multiple disorders and have no physician to manage their overall health. The article concludes with the contact information for the Interstitial Cystitis Association (www.ICHELP.org ). 21 references.

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Epidemiology of Interstitial Cystitis: A Population Based Study Source: Journal of Urology. 161(2): 549-552. February 1999. Summary: Interstitial cystitis is a chronic and debilitating syndrome, but surprisingly little is known about its epidemiology. This article reports on a study designed to estimate the prevalence of interstitial cystitis (IC) among women in the United States. Female participants in the Nurses' Health Study (NHS) I and II (n = 184,583) were asked by mailed questionnaires whether they had ever been diagnosed with IC. The authors requested and reviewed medical records of the women who reported having IC. The accuracy of self reports was evaluated using standardized criteria. Among the 93,428 women who responded to the NHS II questionnaire and 91,155 women who responded to the NHS I questionnaire, 1,354 (1.4 percent) and 357 (0.4 percent), respectively, self reported IC. Based on medical record review, 63 cases of IC were confirmed in NHS II and 47 in NHS I. The prevalence of IC was 67 per 100,000 women in NHS II and 52 per 100,000 in NHS I. There was no substantial variation in prevalence by age. The authors conclude that these data show the prevalence of IC in the United States to be more than 50 percent higher than previously reported and threefold higher than in Europe. 2 tables. 15 references. (AA-M).

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Interstitial Cystitis as an Infectious Disease Source: Urologic Clinics of North America. 21(1): 31-39. February 1994. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Interstitial cystitis is a debilitating, painful bladder disease of unknown cause and with no effective prevention or treatment. In this article, the author presents a hypothesis that interstitial cystitis is an infectious disease. The author discusses the clinical, pathologic, and therapeutic facts about interstitial cystitis; discusses several theories of the pathogenesis of interstitial cystitis; and looks at the evidence for and against infectious disease as a cause. 2 figures. 1 table. 74 references. (AA-M).

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ABCs of Interstitial Cystitis: A Primer for Midlevel Providers Source: Physician Assistant. 24(12): 22, 25-28, 37. December 2000. Contact: Available from Springhouse Corporation. Physician Assistant, P.O. Box 908, Springhouse, PA 19477. (215) 646-8700. Fax (215) 646-4399. Summary: Interstitial cystitis is a relatively uncommon cause of chronic and severe pelvic pain in women aged 40 to 60 years. This article offers an overview of interstitial cystitis (IC) for physician assistants. While predominantly a female disorder (90 percent), IC does occur in men. IC is a noninfectious, inflammatory disease of the bladder characterized by urgency, frequency, suprapubic pain, dyspareunia (painful sexual intercourse), and nocturia (getting up at night to urinate). Making a correct diagnosis requires a high index of suspicion within the primary care setting because there are few physical examination findings. The author cautions that IC often has a profound impact on a patient's quality of life, especially when the diagnosis is missed or delayed. The author discusses demographics, etiology (autoimmune hypothesis, leaky epithelium hypothesis, and mast cell hypothesis), clinical manifestations of IC, physical findings, differential diagnosis, diagnosis (urinalysis, cystoscopy), and treatment options, including therapeutic hydrodistension, intravesicular instillation, oral medications, and surgical treatments. The author also reviews the course of the disorder, including the incidence of remission, the psychological impact of IC, and the great need

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for social support mechanisms to help patients cope with IC. One sidebar offers the contact information for the Interstitial Cystitis Association (ICA), an organization that provides a network of current information and education and a national registry and support system for people with IC. The author concludes that although all treatments are palliative, not curative, it is important for the patient with IC to know that the symptoms can be effectively managed in most cases. 1 table. 32 references. •

Clinical Conversations: Nurses Who Work with Patients with Interstitial Cystitis Source: Urologic Nursing. 20(2): 109-110, 115-118. April 2000. 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: Nurses who work with patients with interstitial cystitis (IC) agree that these patients demand considerable clinician time. This continuing education article shares conversations with nurses who work with this population, addressing patient issues and offering specific nursing advice. IC is a chronic disease with several etiologic theories explaining the syndrome. Because of their symptoms, many IC patients not diagnosed or successfully treated have difficulty fulfilling work responsibilities; marital and sexual relations can suffer; and recreational activities are often discontinued. The authors discuss the role of the knowledgeable clinic nurse who can triage the calls from patients, present pertinent data to the physician, and then call the patient back to implement any changes. Patients with IC who feel that they are receiving adequate attention will become less anxious and demanding. With renewing confidence, these patients can recognize that they are the most important members of the team seeking resolution of their urologic symptoms. The authors address the issues of pain, helping male patients with IC, multimodality therapies, and nursing tips in the areas of managing intravesical bladder installations, sexuality questions, and lifestyle adjustments that may be useful (including the use of warm sitz baths, heating pads, loose fitting clothing, and rest). The authors conclude that clinic nurses can help educate and support IC patients, coordinate care as a liaison between the urologist and patient, and offer helpful tips and resources. Attitude and communication skills are essential. Appended to the article is the posttest with which readers can qualify for 2 hours of continuing education credits. 14 references.

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Coping Strategies in Patients with Interstitial Cystitis: Relationships with Quality of Life and Depression Source: Journal of Urology. 169(1): 233-235. January 2003. 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: Previous research has demonstrated that interstitial cystitis (IC) patients experience depressive symptoms and decrements to quality of life. However, the extent to which patients may be able to influence quality of life and depressive symptoms through coping strategies has not been investigated in this population. This article reports on a study that investigated the association of coping strategies with depressive symptoms, quality of life, and self-reports of pain. A total of 64 females with IC completed questionnaires assessing these factors. Patients coping by greater catastrophizing reported greater impairments in various domains, including depressive symptoms, general mental health, social functioning, vitality, and pain. Greater venting was associated with greater depressive symptoms and poorer mental health. Seeking instrumental social support was associated with fewer depressive symptoms. These

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findings suggest that maladaptive coping strategies are associated with higher levels of depressive symptoms and quality of life decrements in patients with this condition. The authors conclude that psychosocial interventions aimed at increasing adaptive coping may positively impact the female experience with IC. 2 tables. 25 references. •

Depressive Symptoms and Quality of Life in Patients With Interstitial Cystitis Source: Journal of Urology. 167(4): 1763-1767. April 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: Previous research suggests that patients with interstitial cystitis (IC) have poorer quality of life and higher levels of depressive symptoms. However, most studies to date have been limited by the lack of standard measures to describe the experience of living with IC. In addition, no study has used a structured interview to assess depressive symptomatology. This article reports on a study that investigated the extent of depressive symptoms and impaired quality of life in a sample of female patients with interstitial cystitis compared with healthy controls. Relationships among physician rated symptom severity, quality of life, and depressive symptoms were also examined. At a clinic visit, 65 female patients previously diagnosed with IC and 40 age matched, healthy controls completed questionnaires on depressive symptoms and quality of life, and a structured interview on depressive symptoms with trained interviewers. Patients reported compromised quality of life compared with healthy controls across various domains, including physical functioning, ability to function in one's normal role, and vitality. They also had more severe depressive symptoms on the 2 depression measures. In patients, greater interstitial cystitis severity was associated with greater compromise in physical and social functioning, and mental health but not in other quality of life domains or depressive symptoms. The authors conclude that a diagnosis of IC is related to poorer functioning in various life domains and decrements increase with disease severity. 3 figures. 2 tables. 27 references.

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Urinary Tract Infections in the Elderly Source: Current Urology Reports. 2(4): 330-333. August 2001. Contact: Current Science, Inc. 400 Market Street, Suite 700, Philadelphia, PA 19106 (800) 427-1796. Fax (215) 574-2225. E-mail: [email protected]. Website: http://www.current-reports.com. Summary: The elderly population is now increasing in the world. A higher incidence of bacteriuria (bacteria in the urine) and urinary tract infection (UTI) is observed in elderly patients, in both long-term care (LTC) facilities and at home. The management of elderly patients with UTI is increasing in clinical significance. Almost all UTI in the elderly is complicated, rather than simple, UTI. Control of the underlying diseases in the urinary tract is quite important in the management of UTIs in elderly patients. For patients with pyelonephritis (kidney inflammation), the author recommends switch therapy using aminoglycosides and fluoroquinolones, carbapenems, third-generation cephalosporins, or penicillins as selections of choice. The recommended duration of treatment for patients with pyelonephritis is 14 days. Seven to 10 days of treatment using fluoroquinolones or trimethoprim-sulfamethoxazole is recommended for the treatment of elderly patients with symptomatic cystitis (bladder infection). Although asymptomatic bacteriuria is quite common in the elderly population, antibiotic treatment has no benefit for such patients. Intravaginal estrogen replacement is one of

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the choices for the prevention of recurrent UTIs in postmenopausal women. 27 references. •

Practice Guidelines for the Treatment of Uncomplicated Cystitis Source: Current Urology Reports. 2(4): 326-329. August 2001. Contact: Current Science, Inc. 400 Market Street, Suite 700, Philadelphia, PA 19106 (800) 427-1796. Fax (215) 574-2225. E-mail: [email protected]. Website: http://www.current-reports.com. Summary: The Infectious Diseases Society of America has published guidelines for the treatment of uncomplicated cystitis (bladder infection). This article reviews uncomplicated UTIs, i.e., those in healthy, adult, nonpregnant women with normal urinary tract structure and function and in the absence of recent urinary tract instrumentation. Standard therapy is 3 days of trimethoprim and sulfamethoxazole (TMP SMZ) or trimethoprim alone, in those regions where less than 10 to 20 percent of Escherichia coli that cause such infections is resistant to TMP SMZ. In those regions where resistance is higher, the committee recommended using an oral fluoroquinolone for 3 days. Alternatives such as nitrofurantoin for 7 days or fosfomycin as single-dose therapy need more study. These recommendations were established in the late 1990s as resistance to TMP SMZ among uropathogens was increasing in the United States, a phenomenon earlier observed in other parts of the world. Clinicians should be alert to patients infected with possibly resistant organisms, for example, patients who have recently been hospitalized or who are already receiving antibiotics. 1 table. 19 references.

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Diagnosis of Interstitial Cystitis Revisited: Lessons Learned from the National Institutes of Health Interstitial Cystitis Database Study Source: Journal of Urology. 161(2): 553-557. February 1999. Summary: The lack of a precise working definition of interstitial cystitis (IC) may have resulted in clinicians de facto use of the National Institute of Diabetes and Digestive and Kidney Diseases' (NIDDK) 'research' definition. This article reports on a study that evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database Study to determine their utility in clinical practice as a useful basis for the diagnosis of IC. The study included a total of 379 women who met the basic criteria of urinary frequency, urgency, or pain for at least 6 months in duration without a diagnosable etiology. Of these patients, 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of IC and those who met the NIDDK research definition of the syndrome. Almost 90 percent of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have IC, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60 percent of patients regarded by researchers as definitely having IC or likely to have it. The authors conclude that the NIDDK criteria are too restrictive to be used by clinicians as the diagnostic definition of IC. An appendix lists the NIDDK diagnostic criteria. 2 figures. 15 references. (AA-M).

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Idiopathic Sensory Urgency and Early Interstitial Cystitis Source: International Urogynecology Journal. 4(1): 43-49. February 1993.

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Summary: The sensory aspects of bladder function are not clearly defined, poorly understood, and imperfectly managed. Sensory urgency or bladder hypersensitivity often present with symptoms without an obvious cause (idiopathic sensory urgency). This article reviews the evidence that some of these symptomatic patients are actually suffering from early interstitial cystitis. The implications of such a possibility are discussed and the possible role of detrusor mast-cell infiltration in the genesis of bladder symptoms in women is examined. 1 figure. 3 tables. 50 references. (AA). •

Different Approaches to the Management of Interstitial Cystitis Source: Innovations in Urology Nursing. 5(3): 46-48, 51. 1994. Contact: Available from Meniscus Educational Institute. Mulberry Atrium North, 105 North 22nd Street, Suite 210, Philadelphia, PA 19103-1302. (215) 564-4600. Fax (215) 5644601. Summary: The symptoms associated with interstitial cystitis (IC) can decrease function and quality of life. This article presents a clinician's nontraditional perspective on treating the patient with IC. The author describes the antibiotic therapy and musculoskeletal treatments she uses as part of an individualized program to reduce symptoms in patients with IC and urgency or frequency syndromes. A thorough evaluation, individualized approach, compassion, and a continued focus on the goals of treatment are emphasized. Goals of treatment include relief of pain, increased function, adequate sleep, and dietary adequacy. 3 figures.

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How do Patients with Interstitial Cystitis Present? Source: Journal of Urology. 166(6): 2118-2120. December 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. Summary: The typical patient with interstitial cystitis has symptoms for 4 to 7 years before the correct diagnosis is made. Because patients do not typically present with a full constellation of symptoms, it is worthwhile to understand how the earliest symptoms present. This article reports on a study undertaken to determine how interstitial cystitis (IC) progresses from initial symptoms to diagnosis. The authors retrospectively analyzed the records of 45 patients to determine the dates of symptom onset and diagnosis, and sequence of urgency or frequency, nocturia (urinating at night), and pain. The authors also documented alternate and previous diagnoses, and previous surgical treatments. Of the patients, 89 percent presented with only 1 symptom. Median time from the initial symptom to all symptoms was 2 years (mean 5.5 years). The most common previous diagnoses were urinary infection in 19 cases, a gynecologic diagnosis in 14, and urethral diagnoses in 6. A previous urinary infection was documented in only 1 of 19 patients, while 11 had undergone hysterectomy and 5 diagnosed with endometriosis had no pathological documentation available. The authors note that clinicians may fail to appreciate the symptoms of early interstitial cystitis, which leads to delayed diagnosis until the patient is more symptomatic. The authors stress that IC should be considered when laboratory documentation for alternate diagnoses is lacking or when patients fail to respond to therapy for alternate diagnoses. 1 table. 17 references.

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Is It Interstitial Cystitis? Diagnostic Distinctions in Reduced Bladder Capacity Source: Contemporary Urology. 6(7): 13-22. July 1994.

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Contact: Available from Medical Economics Publishing Inc. Montvale, NJ 07645. (800) 432-4570. Summary: This article addresses the questions involved in the diagnostic distinctions between interstitial cystitis (IC) and other causes of reduced bladder capacity. Topics include difficulties in diagnosing IC; the physiology of bladder sensation; an historical review of IC; clinical terminology used, including sensory urgency, motor urgency, bladder pain, maximum cystometric capacity, and bladder compliance; the role of urodynamic testing; differential diagnosis, including bladder cancer and carcinoma in situ (CIS), radiation cystitis, cyclophosphamide cystitis, detrusor instability, malakoplakia, schistosomiasis, tuberculous cystitis, and eosinophilic cystitis; the diagnostic approach; and how the NIH defines IC. An algorithm summarizing the work-up of suspected IC is included. 3 figures. 1 table. 17 references. •

Treatment of Refractory Interstitial Cystitis Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 7(3): 215220. 1996. Contact: Available from Springer-Verlag New York, Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Fax (212) 473-6372. Summary: This article addresses the treatment of refractory interstitial cystitis (IC), a typically therapeutically frustrating condition of the urinary tract. The authors note that among the vast array of treatments available, none is particularly effective. As the majority of patients fail to experience a significant and prolonged response to standard treatments, new options are frequently being developed. These include the oral administration of cimetidine, the intravesical use of hyaluronic acid and BCG, and total cystectomy with the formation of a continent urinary diversion. Unfortunately, the acceptance of many new treatments is based on incomplete evaluation, and this has resulted in a confusing array of disparate alternatives. The authors conclude that effective and durable treatment will not be available until the nature of the disease is better understood and the mechanisms of action of current therapies are elucidated. An algorithm outlining a suggested approach to treatment of IC is provided. 1 figure. 44 references. (AA-M).

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Interstitial Cystitis: Successful Management by Increasing Urinary Voiding Intervals Source: Urology. 37(3): 207-212. March 1991. Summary: This article describes a new technique of managing interstitial cystitis by initiating a new voiding pattern designed to increase bladder capacity and decrease urinary urgency. The article reports on the authors' experience with a group of 21 patients. Overall, 71 percent (n=15) had successful management of their symptoms and reported a 50 percent decrease in their symptoms of urinary urgency, frequency, and nocturia. Nineteen percent (n=4) reported 25 percent decrease in symptoms and 10 percent had no change. The authors note that presence of significant pain adversely affects outcome. Therapy success appears to be enhanced by good patient education plus an emphasis on patience and compliance together with monthly visits to the urologist to monitor progress. 2 figures. 6 tables. 5 references. (AA-M).

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Urine Markers of Interstitial Cystitis Source: Urology. 57(6A Supplement): 15-21. June 2001.

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Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: This article describes the current state of the art with regard to urine markers of interstitial cystitis (IC) and describes the areas that need continuing research. The author reviewed articles referenced in MEDLINE that describe urine alterations in IC; additional articles were identified by cross-referencing. The different marker alterations were tabulated. The relevant articles are discussed, with a focus on different purposes for urine markers including diagnosing IC, confirming a specific pathophysiology for IC, and predicting or following response to a specific treatment. Currently, 2 markers (glycoprotein 51 and antiproliferative factor, APF) clearly separate IC and control subjects, with minimal overlap. Markers that correlate with specific bladder biopsy features include 1,4-methylimidazole acetic acid and eosinophil cationic protein (ECP), which correlate with mast cell density, and interleukin (IL) 6, which correlates with mononuclear inflammation. The author summarizes the markers that changed after treatment. The author concludes that a large number of urine alterations have been reported, and a few are being pursued further by correlating with bladder biopsy findings or treatment responses. 2 tables. 50 references. •

Urinary Tract Infection: Selecting the Optimal Agent Source: Drug Therapy. 21(3): 27-32, 37. March 1991. Summary: This article discusses selecting the optimal agent to treat urinary tract infections. The author stresses that agent selection must take into consideration cost, convenience, likelihood and severity of adverse effects, spectrum of antibacterial activity, and efficacy in specific urinary tract infection syndromes. Acute cystitis in women without complicating factors is usually best treated with short-course (singledose or three-day) therapy with an oral agent, while longer treatment courses are reserved for men and for women with complicating factors. Acute pyelonephritis usually requires intravenous therapy with a single agent or a combination regimen active against gram-negative bacilli; mild cases can be successfully treated with oral agents on an outpatient basis. 5 tables. 9 references. (AA-M).

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Epidemiology of Interstitial Cystitis Source: Urologic Clinics of North America. 21(1): 7-20. February 1994. Contact: Available from W.B. Saunders Company. The Curtis Center, Independence Square West, Philadelphia, PA 19106. (800) 654-2452. Summary: This article discusses the epidemiology of interstitial cystitis (IC), a chronic idiopathic inflammatory bladder disease syndrome of unknown cause and pathogenesis. The author reports on a study in which information on demographics, risk factors, symptoms, pain, and psychosocial factors was elicited from over 300 patients who had been diagnosed as having IC; this study is augmented with relevant information on 246 other IC patients. The author examines the combined database for epidemiologic factors that might enhance understanding of the nature of this disorder. The author notes that improvement in the mental and social well-being of IC patients presents an important challenge to urologists, who traditionally have focused solely on physiologic dimensions and parameters of patients' health. 4 figures. 24 tables. 34 references.

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Battle of the Bladder: The Pathogenesis and Treatment of Uncomplicated Cystitis Source: International Urogynecology Journal. 1(4): 218-222. December 1990. Summary: This article discusses the pathogenesis and treatment of uncomplicated cystitis in women. An ecological approach to the pathogenesis of uncomplicated urinary tract infections allows awareness of the continual battle being waged in the vagina, urethra, and bladder between the bacterial invaders and the host defense mechanisms. Despite overwhelming odds, the bacteria must be able to persist, colonize, and finally adhere to these various battlefields on their ascent to the bladder itself. The large number of patients presenting to physician offices with acute simple cystitis attests to the fact that the bacteria occasionally win the battle of the bladder. An understanding of the pathophysiology of this constantly raging battle is crucial to enable physicians to modify the clinical approach to women with simple uncomplicated urinary tract infections. 1 table. 7 references. (AA-M).

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Urinary Tract Infections in Women Source: American Family Physician. 41(2): 565-571. February 1990. Summary: This article discusses urinary tract infections in women and notes that the clinical conditions that cause dysuria in women can usually be differentiated by the history and selected physical and laboratory examinations. Cystitis can be treated with short-course therapy in uncomplicated cases. Pretreatment cultures are usually not necessary, since most infections are caused by 'Escherichia coli.' Outpatient treatment of pyelonephritis is appropriate in selected patients. Follow-up culture after treatment of either cystitis or pyelonephritis is indicated to identify those patients requiring longer treatment or urologic evaluation. The article recounts research that suggests that recurrent urinary tract infections can be managed with postcoital antibiotics, long-term prophylaxis or patient self-administration of short-course therapy. The article stresses that bacteriuria and pyelonephritis in pregnancy must be aggressively diagnosed and treated. 26 references. 5 tables (AA-M).

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Interstitial Cystitis: Urgency and Frequency Syndrome Source: American Family Physician. 63(7): 1199-1206. October 1, 2001. Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. Summary: This article familiarizes family physicians with the latest thinking on interstitial cystitis (IC), a chronic, severely debilitating disease of the urinary bladder. Excessive urgency and frequency of urination, suprapubic pain, dyspareunia (painful sexual intercourse), chronic pelvic pain, and negative urine cultures are characteristic of IC. The course of the disease is usually marked by flare-ups and remissions. Other conditions that should be ruled out include bacterial cystitis, urethritis, neoplasia, vaginitis, and vulva vestibulitis. Glomerulations or Hunner's ulcers found at cystoscopy confirm the diagnosis. Oral treatments for IC include pentosan polysulfate, tricyclic antidepressants, and antihistamines. Intravesicular (in the bladder) therapies include hydrodistention, dimethyl sulfoxide (DMSO), and heparin, or a combination of agents. The author stresses that referral to a support group should be offered to all patients with IC. A patient information handout on IC, written by the author of this article, is provided in the same issue. 5 figures. 2 tables. 35 references.

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Interstitial Cystitis: When Urgency and Frequency Mean More Than Routine Inflammation Source: Postgraduate Medicine. 99(5): 201-204, 207-208, 214. May 1996. Summary: This article familiarizes readers with interstitial cystitis (IC). The authors provide tips for primary care physicians on making a presumptive diagnosis and suggest symptomatic relief methods to try before referral. Topics include the possible causes of IC; patient characteristics; risk factors; differential diagnosis; coping tips for patients with IC; and treatment methods, including oral medications, bladder hydrodistention, intravesical therapy, surgery, and other methods. The article concludes with some recommendations for primary care treatment. The authors stress that many patients respond to some form of therapy and may even have long-term remissions. However, arriving at the form of therapy that relieves symptoms in a given patient is often a trial-and-error process. 2 tables. 16 references. (AA-M).

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Interstitial Cystitis: Diagnosis and Treatment Source: Innovations in Urology Nursing. 5(3): 38-43. 1994. Contact: Available from Meniscus Educational Institute. Mulberry Atrium North, 105 North 22nd Street, Suite 210, Philadelphia, PA 19103-1302. (215) 564-4600. Fax (215) 5644601. Summary: This article is designed to familiarize nurses with the diagnosis and treatment of interstitial cystitis (IC), a condition characterized by urinary frequency, urgency, and pain in the bladder, urethra, and/or vagina. Topics include a description of the classic patient with IC; etiological factors; criteria that indicate a diagnosis of IC; and possible treatment options for IC. Treatment options discussed include behavioral measures, including dietary modifications; systemic medications; intravesical therapies; transcutaneous electrical nerve stimulation (TENS); and open surgery. The author concludes that patient support, education, and participation are essential in managing this disease. 3 tables. 16 references.

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Clinical Highlights: Management of Interstitial Cystitis Source: Urologic Nursing. 14(3): 145-148. September 1994. Summary: This article presents a chart that summarizes the management of interstitial cystitis. After a brief introductory section, the author presents a nontraditional, comprehensive, total-patient treatment approach to interstitial cystitis, with the following treatment goals: relief of pain, increased function, adequate sleep, and adequate dietary intake. Included in the chart are various modalities of treatment, including antibiotic therapy, musculoskeletal factors, diet, bladder training, bowel training, biofeedback, yeast control, sleep, and relief of premenstrual and menstrual symptoms. For each modality, the author provides a treatment description and/or rationale and the specifics of treatment, including administration and dosage recommendations, nutritional guidelines, and behavior modification.

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Collaborative Approach to Managing Interstitial Cystitis Source: Urology. 49(Supplement 5A): 10-13. May 1997. Summary: This article presents a collaborative approach to the patient care management of people with interstitial cystitis (IC), a chronic, painful inflammatory disease of the bladder wall. The authors hope to establish that conventional protocols often do not

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provide an adequate framework for managing IC. They also describe the special role of the urologic caregiver in developing a collaborative relationship with IC patients that can allay fears and provide hope for coping with this disease. The authors reviewed epidemiologic studies and used clinical experience with IC patients and their physicians to develop their rationale. They stress that the symptoms of IC (pain, urgency, and urinary frequency) can have a profoundly disruptive effect on patients' lives and present unique challenges to physicians as urologic caregivers. The impact of IC on patients' lives needs to be accounted for empathetically, and appropriate referrals for depression, sexuality, or relationship problems should be made. Pain should be managed aggressively, and patients who have had delayed diagnosis or who have not responded to the traditional treatments should be educated about the array of medical, alternative, and self-help modalities available. The authors conclude that a successful treatment paradigm requires that physicians and patients be knowledgeable about the array of medical and alternative therapies and that these be applied in a systematic but creative way. Through empathic support, information, and a flexible treatment protocol, patients will learn to trust the medical process and take an active part in the management of IC. 12 references. (AA-M). •

Understanding Interstitial Cystitis Source: Journal of Urological Nursing. 12(1): 367-371. January/February/March 1993. Summary: This article presents a review of interstitial cystitis (IC), focusing on a holistic nursing approach to the patient with IC. Topics covered include the etiologies of IC, clinical presentations, the physical exam, diagnostic tests used to determine IC, and treatment choices, including hydrodilation, fulgeration, medications, intravesical agents, investigational medications, behavior modification, electrical stimulation, dietary control, and surgery. The author stresses that, because of the disabling nature of IC and its chronicity with frequent relapses, it is important to educate patients concerning this disorder and to recommend participation in support groups. 15 references.

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Observations on the Presentation, Diagnosis, and Treatment of Interstitial Cystitis in Men Source: Urology. 57(6A Supplement): 26-29. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: This article presents and evaluates the symptoms, presentation, diagnosis, and treatment of men with interstitial cystitis (IC). The authors performed a retrospective chart review and an interview of all men in their practice diagnosed with IC since 1990. The patients' presenting symptoms, physical findings, clinical evaluation, and responses to therapy were reviewed. A total of 52 men were identified during the study who met the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria for diagnosis of IC. The most common referral diagnosis was prostatitis with the most common predominant symptoms being suprapubic pain with urinary frequency and dysuria (painful urination). A significant number of male patients also developed sexual dysfunction. All patients met the NIDDK criteria for a diagnosis of IC. Multiple therapies were used for the treatment of these patients over the study period. Five patients were initially treated with dimethyl sulfoxide (DMSO) as a sole agent; however, all intravesically treated patients eventually failed this form of therapy. A total of 37 of 52 patients were treated with multidrug oral therapy. Findings showed that 80 percent of patients achieved greater than 75 percent improvement in

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their symptomatology at 6 months followup with a durable response at 1 year. The authors conclude that IC in men is probably underdiagnosed and is most commonly misdiagnosed as prostatitis. The patient's presentation is analogous to that in the female population, allowing for gender differences. 5 tables. 18 references. •

Urinary Tract Infection: Current Management Strategies Source: Postgraduate Medicine. 100(5): 229-236, 239. November 1996. Summary: This article provides a practical review of current approaches to the evaluation and treatment of urinary tract infection (UTI). Topics include definitions; pathogenic factors; host defenses; predisposing factors for UTI including aging, diabetes, urinary tract calculi, and obstruction; causative organisms; and management strategies for acute uncomplicated cystitis, recurrent cystitis, and uncomplicated pyelonephritis, complicated UTI, catheter-related infection, UTI in men, and asymptomatic bacteriuria. The author notes that, in some cases, the causative organisms are highly predictable and empirical therapy without pretreatment culture is recommended. Other infections (e.g., pyelonephritis) require at least 10 days of antimicrobial therapy, and if complications are present, hospitalization may be warranted. 2 figures. 2 tables. 25 references. (AA-M).

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Interstitial Cystitis: Progress Against Disabling Bladder Condition Source: FDA Consumer. 29(9): 28-30. November 1995. Contact: Available from Superintendent of Documents. P.O. Box 371954, Pittsburgh, PA 15250-7954. Summary: This article provides general information about interstitial cystitis (IC) and the progress being made in understanding IC, including its treatment. Topics include the symptoms of IC; the hypotheses regarding the cause of IC; diagnostic tests; treatment options, including the instillation of DMSO, drug therapy, diet therapy, and surgery. The author describes one woman's experiences with IC. One sidebar summarizes the symptoms of IC. The addresses and phone numbers for the Interstitial Cystitis Association and the American Foundation for Urologic Disease are also provided.

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Comparison of Multiple Urine Markers for Interstitial Cystitis Source: Journal of Urology. 167(6): 2461-2469. June 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 measured several urine markers in 24 hour specimens from female patients with interstitial cystitis (IC, n = 36) and from healthy female controls (n = 36). For each marker, the authors determined whether the urine level was significantly different in IC and in control cases, and whether the marker level correlated with the symptom score. Certain markers were significantly increased in IC, including anti-proliferative factor, epidermal growth factor, insulin-like growth factor (IGF) binding protein-3, and interleukin (IL) 6. Markers significantly decreased in IC were heparin-binding epidermal growth factor-like growth factor, cyclic guanosine monophosphate, and methylhistamine. Other markers were not significantly different in the IC and control groups, including total glycosaminoglycans, epitectin, hyaluronic acid, IL-8, IL-1, and nitrates plus nitrites. The only significant association of marker with symptom score was a positive correlation of IL-6 with

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nocturia. For all markers the conclusions were the same whether the marker was normalized to creatinine or to 24 hours. The authors conclude that of all markers studied, anti-proliferative factor had the least overlap in the IC and control groups, and so it is the most likely candidate to become a diagnostic test. 7 figures. 3 tables. 35 references. •

Does the Potassium Stimulation Test Predict Cystometric, Cystoscopic Outcome in Interstitial Cystitis? Source: Journal of Urology. 168(8): 556-557. August 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 that establishes the relationship among symptom duration, cystometric and cystoscopic findings, and the potassium stimulation test in patients with interstitial cystitis (IC). The authors performed a retrospective chart review of 189 patients who were treated at an ambulatory clinic between 1992 and 1998. Of the 189 patients diagnosed with IC, 173 (92 percent) were female and 16 (8 percent) were male. The potassium stimulation test was positive in 105 patients (83 percent), negative in 16 patients (13 percent) and equivocal in 6 patients (4 percent). A cystometrogram and potassium stimulation test were done in 118 patients. Bladder capacity averaged 259 milliliters in patients with tests potassium positive and negative, while average bladder volume at first sensation to void was 85 milliliters and 148 milliliters in those with negative and positive tests, respectively. Among the 102 patients with a positive potassium stimulation test, 52 had normal cystoscopic findings. The authors conclude that the potassium stimulation test is not correlated with either bladder capacity or cystoscopic findings. Nevertheless, considering that no specific diagnostic test exists for IC, the authors have found the potassium stimulation test to be helpful in cases when clinical presentation is challenging. 2 tables. 8 references.

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Biopsy Features are Associated with Primary Symptoms in Interstitial Cystitis: Results from the Interstitial Cystitis Database Study Source: Urology. 57(6A Supplement): 67-75. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: This article reports on a study undertaken to investigate associations between bladder biopsy features and urinary symptoms for patients enrolled in the Interstitial Cystitis Database (ICDB) Study. Bladder biopsies were obtained during baseline screening in the ICDB Study and were evaluated for histopathologic (disease of the cells) features. Among 204 interstitial cystitis (IC) patients providing biopsy specimens, cystoscopic pathology findings were not statistically associated with primary IC symptoms, although the presence of Hunner's ulcer (n = 12) was suggestive of increased urinary frequency. Within a multivariable predictive model for nighttime voiding frequency, adjusting for age and minimum volume per void, 4 pathology features were noted: mast cell count in lamina propria on tryptase stain; complete loss of urothelium; granulation tissue in lamina propria; and vascular density in lamina propria on factor VIII (F8) stain were statistically significant. Similarly, in a multivariable model for urinary urgency, minimum volume and percentage of submucosal granulation tissue remained statistically significant. Finally, the percent of mucosa denuded of urothelium and the percentage of submucosal hemorrhage (bleeding) remained highly associated with pain in a multivariable predictive model. The fact that the presence or severity of

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glomerulations was not selected for any of these predictive models suggests that cystoscopic findings of glomerulations are not predictive of IC symptoms. 2 figures. 7 tables. 23 references. •

Natural History of Interstitial Cystitis: A Survey of 374 Patients Source: Journal of Urology. Volume 149: 465-469. March 1993. Summary: This article reports on an epidemiological survey directed at determining the natural history of interstitial cystitis (IC). Information on demographics, risk factors, symptoms, pain and psychosocial factors was elicited from 374 patients who had all been diagnosed as having IC. Patients were predominantly female (89.8 percent) and white (94.1 percent). Information on 25 potential risk factors included 44.4 percent of the women reporting hysterectomy, 38.2 percent of the patients having strong sensitivities or allergic reactions to medication, and only 2.7 percent having diabetes. Other data collected included IC symptoms of frequency and urgency, pelvic pain, and burning; the role of urination in relieving or lessening IC pain; medication; behaviors that increased IC pain; fatigue and depression; and activities of daily living, including travel, employment, leisure activities, and sleeping. The researchers note that there is an apparent plateau in the frequency and urgency among patients after approximately five years with symptoms. 2 figures. 6 tables. 19 references. (AA-M).

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Cystitis as a Correlate of Female Urinary Incontinence Source: International Urogynecology Journal. 5(3): 135-140. 1994. Contact: Available from Springer-Verlag New York, Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Summary: This article reports on research undertaken to study the association between urge and stress urinary incontinence (UI) and a history of cystitis in adult females. A cross-section of the adult female population, aged 30-59 years, in the Municipality of Aarhus, Denmark, was studied, using self-reported data based on postal questionnaires. The main measurements were period prevalence in 1987 of episodes of UI provoked by physical stress and UI associated with a feeling of urge; prevalence of experience of episodes of cystitis and UI related to cystitis in adult life; and prevalence of relative risks, as indicated by odds ratio, of UI conditional on cystitis experience. The authors concluded that cystitis may be an important component of UI etiology. Data showed that stress and not urge UI seems to be the key type related to a history of cystitis in general. The experience of UI during cystitis is connected to both stress and urge UI. 7 tables. 23 references. (AA-M).

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Hemorrhagic Cystitis: Not Totally Intractable Source: Contemporary Urology. 2(3): 27-30, 32-34, 43. April 1990. Summary: This article reports on the many options that exist for treating hemorrhagic cystitis, or stubborn bladder bleeding. The authors describe early treatment, first-and second-line therapies, and surgical approaches. Potential complications and precautions for various therapies are described. Additional techniques that are currently being evaluated for treatment are discussed. While no one treatment guarantees complete or sufficient hemostasis, the authors note that most patients respond to simple bladder irrigation with complete evacuation of clots, and possibly electrocoagulation. Formalin installation may be the next most useful approach. Conservative treatment is often

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preferred, but if necessary, urinary diversion with or without cystectomy may be performed. (AA-M). •

Use and Effectiveness of Physical Self-Care Strategies for Interstitial Cystitis Source: Nurse Practitioner. 19(10): 55-61. October 1994. Contact: Available from Elsevier Science Publishing Company. 655 Avenue of the Americas, New York, NY 10010. (212) 989-5800. Summary: This article reports on the use and effectiveness of physical self-care strategies in preventing symptoms or managing mild to moderate symptoms of interstitial cystitis (IC). The authors analyze the results from a survey questionnaire on self-care strategies that was completed by 138 members of the Interstitial Cystitis Association. Subjects indicated how often they used more than 300 self-care strategies and the effectiveness of these strategies. The authors report findings from five physical subdomains: medications, treatments, hygiene, diet, and body comfort. Among those who reported using the methods, the effectiveness ratings for many body comfort strategies were comparable to the reported effectiveness of medications (including narcotics) for managing mild to moderate symptoms. 6 tables. 26 references. (AA-M).

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Short Course of Antibiotics and Low Fluid Intake Promote Cure in Cystitis Source: Contemporary Urology. 7(5): 44-46, 48, 50-52, 55. May 1995. Contact: Available from Medical Economics Publishing. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570 or (201) 358-7200. Summary: This article reviews how to manage acute cystitis with short course antibiotic therapy and notes the rationale for low fluid intake during treatment. Topics include the pathophysiology of uncomplicated urinary tract infection (UTI); diagnosis; treatment principles; antibiotic choices and courses of therapy; and optimal duration of treatment. Antibiotics discussed include trimethoprim, amoxicillin, cephalexin, nitrofurantoin monohydrate/macrocrystals, norfloxacin, ciprofloxacin, and ofloxacin. The author notes that low fluid intake facilitates cure by increasing urinary concentration of antibacterial compounds. The article concludes with a discussion of self-treatment for recurrent, documented infections. 2 figures. 2 tables. 60 references.

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New Concepts in the Etiology and Diagnosis of Interstitial Cystitis Source: Infections in Urology. 9(3): 79, 82-83. May-June 1996. Contact: Available from SCP Communications, Inc. 134 West 29th Street, 4th Floor, New York, NY 10001-5399. (212) 714-1740. Fax (212) 629-3760. Summary: This article reviews new concepts in the etiology and diagnosis of interstitial cystitis (IC). Topics include the role of infection; the role of alteration of the glycosaminoglycan layer of the bladder epithelium; the role of autoimmunity, including mast cells and autoantibodies; the role of reflex sympathetic dystrophy; and the search for objective markers of IC. The authors note that the establishment by NIH of diagnostic criteria has greatly facilitated the standardization of research studies on IC. However, at present the true etiology of IC is unknown, and no clinically relevant biological markers have been conclusively identified to help in establishing its diagnosis. 24 references.

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Cystitis: The Bladder on Fire. What Should You Do? Source: Family Urology. 4(2): 9-12. 1999. 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: This article reviews painful bladder conditions, including bacterial cystitis (urinary tract infections, or UTI) and interstitial cystitis (IC). The author notes that women and their physicians are often unaware of the variety of possible causes and the many effective treatments; indeed, many women are incorrectly diagnosed, offered no or inappropriate treatment, and denied referral for further investigation that may lead to successful therapy. In most cases, the correct diagnosis is strongly suggested by the history and examination of the urine and can be confirmed relatively quickly through basic testing. Other cases are very confusing and require a concerted effort from both the patient and the clinician to achieve success. In most cases of patients with frequent UTIs, no major abnormality will be uncovered and therapy must focus on prevention of the infections, notably with the use of prophylactic antibiotics. After a 3 to 6 month period of prophylaxis, the antibiotic can be discontinued and about two thirds of women will break out of the cycle of recurrent infections. The odds can be improved if the patient makes an effort to increase fluid intake, voids regularly, and regulates the vaginal bacteria by taking acidophilus preparations. In addition, hormone replacement in the postmenopausal female reduces the risk of recurrent infections and should be discussed in the context of the woman's overall health. IC is an inflammation that is not caused by bacteria; the symptoms occur consistently and over a substantial period of time in the absence of infection. IC has a natural course characterized by spontaneous flares and remissions; the author discusses the various risk factors for flare ups. The history is the single most important factor in making the diagnosis of IC; however, it is important to exclude other diseases that could mimic the bladder irritation seen in IC. Although there is no cure for IC, there are many treatments that can address the most bothersome symptoms with minimal side effects. The author briefly reviews bladder distention, DMSO bladder instillations, oral drugs, pain medications, dietary therapy, electrical stimulation (TENS), biofeedback, and acupuncture. The author concludes by reiterating that help is available for almost all patients with bladder pain and frequency who are willing to participate actively in their care.

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Say Goodbye to Cystitis Source: Prevention. p. 48-48-55, 122-123. November 1991. Summary: This article reviews the causes of and treatments for cystitis, or urinary tract infection, in women. Topics include the bacterial connection, the role of female anatomy, diagnostic tests, the varied uses of antibiotics to treat cystitis, chronic or recurrent cystitis, and contributing causes, including sexual intercourse, certain contraceptives, poor voiding habits, and menopause. The author also provides suggestions for diaphragm placement, toileting hygiene, and the role of diet in avoiding recurrent cystitis. The causes of non-bacterial cystitis are also discussed, including: stress, menopause, chemical irritants, birth control, and sexual intercourse.

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Managing Interstitial Cystitis Source: Contemporary Urology. 2(2): 45-49. March 1990.

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Summary: This article reviews the current medical and surgical techniques used to manage interstitial cystitis. The author provides a brief introduction and description of interstitial cystitis, including current theory regarding possible cause. Treatments discussed include hydrodistension of the bladder; drug therapy, including dimethylsulfoxine, heparin, oxychlorosene, and pentosanpolysulfate; autodilation; behavior modification; and surgery, including augmentation cystoplasty, cytolysis or denervation of the bladder, and cystectomy and diversion. The author stresses that one of the conservative therapies described will relieve the symptoms in 70 to 75 percent of patients; for the remainder, cystectomy, diversion, and urethrectomy is the best alternative. 1 table. 8 references. •

Urinary Tract Infections in Pregnancy Source: International Urogynecology Journal. 1(3): 155-163. September 1990. Summary: This article reviews the current research literature on urinary tract infections in pregnancy. Urinary tract infections are the most frequently encountered medical complications of pregnancy. Although urinary tract infections are often asymptomatic in pregnancy, physiological changes associated with the gravid state predispose these patients to the development of acute pyelonephritis resulting in considerable morbidity and mortality. Additionally, urinary tract infection during pregnancy may adversely affect the fetus. The authors contend that an understanding of the etiology, evaluation, and treatment of these infections is essential to the management of pregnant patients. 8 tables. 68 references. (AA-M).

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Cystitis: Not Always a Simple Problem Source: Patient Care. 31(16): 34-36, 39-40, 42, 44, 47. October 15, 1997. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article reviews the standard care for urinary tract infections (UTIs) in women. The authors note that, because the majority of UTIs in female patients are uncomplicated and therefore easily resolved, telephone triage has become fairly routine. Empiric treatment of straightforward symptoms, without an office visit, can save time and money. Candidates for this strategy are women whose previous, culture documented UTIs have responded to brief courses of antibiotics. An earlier assessment has ruled out possible underlying problems, and evaluations at regular intervals ensure that no new complications have developed. Patients should be capable of detailing their symptoms over the phone and must be willing to come into the office if those symptoms fail to respond to a 3 day antibiotic regimen. Telephone diagnoses and treatment are not appropriate for patients with symptoms suggestive of upper UTI, such as chills, fever, flank pain, or hematuria. The same is true of women who have never been treated for UTI. The authors review other situations in which a more detailed workup is required. The authors review the acute drug therapy regimens commonly used, the need for prophylaxis, and the use of nonpharmacologic approaches to help keep the bladder healthy and prevent UTIs. Two sidebars address hematuria (blood in the urine) and obtaining a urine specimen. 1 figure. 1 table. 12 references.

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Standard Intravesical Therapies for Interstitial Cystitis Source: Urologic Clinics of North America. 21(1): 73-83. February 1994.

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Contact: Available from W.B. Saunders Company, Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: This article summarizes the current approaches to intravesical therapy of interstitial cystitis (IC). Topics include treatment goals in IC; an overview of intravesical pharmacotherapy; and intravesical therapies, including bladder hydrodilatation, silver nitrate, sodium oxychlorosene (Clorpactin WCS 90), dimethyl sulfoxide (RIMSO-50), heparin, and newer agents, including pentosanpolysulfate, disodium cromoglycate, and doxorubicin. The authors caution that responses to intravesical lavage are variable in duration, unpredictable, and unamenable to objective measurement. They conclude with a suggested treatment algorithm for IC. 1 figure. 5 tables. 37 references. •

Interstitial Cystitis Update Source: Infections in Urology. 10(3): 75-79, 82. May-June 1997. Contact: Available from SCP Communications, Inc. 134 West 29th Street, New York, NY 10001-5399. Summary: This article updates readers on interstitial cystitis (IC). The author notes that the primary symptoms of IC are chronic urinary frequency associated with urethral, pelvic, or bladder pain, and often dyspareunia. The etiology of IC is likely from a variety of causes, and the syndrome may represent a common pathologic endpoint for several disease processes. Recent evidence makes a strong case for an autoimmune cause. Bacteria undetected by routine urine culture may also contribute to the pathogenesis of IC. Although treatment remains empiric, a variety of oral and intravesical therapies are available. The author describes hydrodistention, oral drugs, intravesical therapy, other agents, narcotics, surgery, and investigational therapies being used to treat IC. Patients with a bladder capacity of less than 250cc may benefit from surgery. The author concludes with a description of current research efforts under way through initiatives by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in conjunction with the Interstitial Cystitis Association. Areas of interest include the role of the bladder epithelium in IC. Bladder epithelial cells can respond to immune stimulation by the production of cytokines and the expression of an activated cell-surface phenotype. Another advancement in the study of this condition is the establishment of an IC database; information is being collected on people with IC in an attempt to better classify and understand the disease. 3 figures. 34 references. (AA-M).

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Infection in the Elderly: Part I: Urinary Tract Infections Source: Infectious Disease Practice. 15(4): 1-7. April 1991. Summary: This article, part of a series on infection in the elderly, discusses urinary tract infections. The authors stress that elderly patients may present with different manifestations of an illness and different pathogens than patients in younger age groups. The authors discuss the typical and atypical presentation of urinary tract infection (UTI), and how it is treated. Six syndromes are discussed: benign bacteriuria of the elderly, catheter-associated bacteriuria, cystitis, pyelonephritis, acute prostatitis, and chronic prostatitis. The authors also discuss the indications for long-term antimicrobial suppressive therapy in this population. 1 table. 16 references.

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Is Interstitial Cystitis an Underdiagnosed Problem in Children? A Diagnostic and Therapeutic Dilemma Source: Urology. 57(6A Supplement): 30-31. June 2001.

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Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: This commentary article considers whether interstitial cystitis (IC) is an underdiagnosed problem in children. In general pediatric practice, as well as in urologic practice, children with various types of voiding dysfunction are rather common, and one can only wonder whether some of these children's problems may be an early manifestation of IC. However, IC is diagnosed primarily as a symptom complex with little or no reliable diagnostic markers, and there are still no established guidelines for diagnosing IC in children. The author cautions that even if IC diagnosis is entertained after identifying typical endoscopic appearance following hydrodistention of the bladder, many of the currently available therapies for IC have not been tested in children for safety and efficacy. The author reports on his own experience as a pediatric urologist and also briefly describes a study of extraordinary urinary frequency problems in children. The author concludes that the problem of understanding IC in children needs to be pursued further. 3 references. •

When to Consider TMP-SMX Resistance in Treating Acute Urinary Tract Infections? (commentary) Source: Consultant. 40(1): 18-20. January 2000. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This commentary, in the form of a letter, offers advice on when to consider TMP SMX resistance in treating acute urinary tract infections (UTIs). The authors note that they recently reported on antibiotic resistance among urinary pathogens that caused acute, uncomplicated cystitis. Resistance of Escherichia coli to TMP and TMP SMX (trimethoprim sulfamethoxazole) rose from 9 percent in 1992 to 18 percent in 1996. The authors also briefly report additional clinical data on the outcomes of patients who receive TMP SMX for UTIs. The authors conclude that, collectively, these data suggest that TMP SMX may no longer be the optimal empiric therapy for women with acute, uncomplicated UTIs, at least in areas where the prevalence of resistance is high. Alternative therapies, such as fluoroquinolone that is primarily excreted through the urine, should be considered for the empiric treatment of UTIs. The letter is published with a further commentary in which Dr. S. G. Mulholland suggests that using the alternative drugs for empiric therapy may be unnecessary because there are many communities where the resistance to TMP SMX is not high. 8 references.

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New Concepts in Interstitial Cystitis (editorial) Source: International Urogynecology Journal. 8(1): 1-2. 1997. Contact: Available from Springer-Verlag New York Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Fax (212) 473-6272. Summary: This editorial introduces recent concepts in treating and understanding interstitial cystitis (IC). The author notes that the majority of females presenting to primary care doctors with urgency and frequency have negative cultures and probably represent milder forms of the IC syndrome. The primary pathogenic mechanism of IC seems to be a defective epithelial permeability barrier (the bladder wall). When this barrier becomes physiologically dysfunctional, it allows the lead of solutes (probably potassium) into the subepithelial spaces. This alone could account for most of the symptom complex, as there is not much to suggest that any of these patients has any

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ongoing inflammatory process. One of the new simple and useful diagnostic tests is to check the patient for potassium 'leakage.' This is done by examining the patient for potassium sensitivity by intravesically instilling a 40 ml solution of water for 5 minutes, followed by a 40 ml solution of potassium chloride. Approximately 70 percent of IC patients will have significant provocation of their symptoms with the intravesical potassium chloride and none with the water. Another useful test is a 3-day voiding log. Perhaps the major breakthrough in therapy has been the use of heparinoids. Heparinlike drugs not only successfully control the symptoms but also reverse the course of the disease when used chronically. It can take 3 to 6 months to show improvement, and 6 to 12 months to work well. It is important to maintain patients on this therapy indefinitely to obtain its beneficial effects. Intravesical heparin is excellent therapy for moderate to severe patients. The author notes that moderate and severe patients are started on a combination of oral Elmiron and intravesical heparin, and then after 6 months are gradually weaned off the heparin. 4 references. •

Interstitial Cystitis: A Bladder Problem Source: American Family Physician. 63(7): 1212-1214. October 1, 2001. Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. Summary: This patient education handout helps readers understand interstitial cystitis (IC), a chronic, severely debilitating disease of the urinary bladder. People with IC may have many of the following symptoms: an urgent need to urinate, both in the daytime and during the night; pressure, pain, and tenderness around the bladder, pelvis and perineum; a bladder that will not hold as much urine as it did before the IC; pain during sexual intercourse (dyspareunia); and, in men, discomfort or pain in the penis or scrotum. In many women, the symptoms get worse before their menstrual period. Stress may also make the symptoms worse, but stress does not cause the condition. The fact sheet discusses the causes of IC, the diagnostic tests that may be used to confirm a diagnosis, treatment options, and lifestyle changes that may contribute to a reduction in symptoms. Treatment options can include dietary changes, bladder distention (with fluid and medications, done under anesthesia), medications, and bladder instillation. Other treatment strategies can include quitting smoking, bladder training, physical therapy, biofeedback, and transcutaneous electrical nerve stimulation (TENS). The fact sheet concludes with the contact information for the Interstitial Cystitis Association (www.ichelp.org) and the National Kidney Foundation (www.kidney.org). A professional education article, written by the author of this handout, is provided in the same issue.

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Management of Urinary Tract Infections in Adults Source: New England Journal of Medicine. 329(18): 1328-1334. October 28, 1993. Summary: This review article highlights recent advances in the treatment of patients in each of five categories of urinary tract infection in adults. The five categories are: young women with acute uncomplicated cystitis, young women with recurrent cystitis, young women with acute uncomplicated pyelonephritis, adults with complicated urinary infection, and all adults with asymptomatic bacteriuria. Management strategies designed for specific groups of patients with urinary infection can maximize therapeutic benefits while reducing costs and the incidence of adverse reactions. The authors emphasize cost-effective strategies that may be particularly important in the coming era of managed care. 1 figure. 2 tables. 60 references.

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Management of Complicated Urinary Tract Infection in Older Patients Source: Journal of the American Geriatrics Society. 44(10): 1235-1241. October 1996. Summary: Urinary tract infection (UTI) in older persons is a common medical problem that is seen in both the ambulatory and institutional settings. This article discusses the management of complicated UTI in older patients. The authors begin by describing the unique aspects of UTI in older persons, particularly as they related to UTI in the younger, general population. The remaining discussion focuses on three complicated clinical circumstances and conditions of UTI in the geriatric population: non-catheter recurrent UTI, asymptomatic bacteriuria, and catheter-related bacteriuria and UTI. 4 tables. 70 references. (AA-M).

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Urinary Tract Infection in Women Source: Journal of the Royal College of Physicians of London. 31(2): 130-133. MarchApril 1997. Contact: Available from Royal College of Physicians of London. Publications Department, 11 St. Andrews Place, Regent's Park, London NW1 4lE, United Kingdom. (020) 7486 5425. E-mail: [email protected]. Website: www.rcplondon.ac.uk. Summary: Urinary tract infection (UTI) is a major health problem, a cause of considerable morbidity among women, and of expense. Most often an isolated event, it becomes recurrent in 10 to 20 percent of women and, in a small but significant number, life threatening. This brief synopsis article reviews the management of UTI in women. UTI usually presents with acute urinary frequency and dysuria (pain on urination). An isolated attack of cystitis (bladder infection) can be confirmed by a bacterial count greater than 100 organisms per milliliter if pyuria (bacteria in the urine) is present and can be treated without bacterial confirmation if the urine dipstick test for pyuria is positive. These cases do not require followup or imaging if cured symptomatically. Recurrent cystitis in a women suggests the use of renal imaging for diagnosis, and if the urinary tract is normal, treatment with three day courses of antibacterials. Cystitis in pregnancy can be treated with nitrofurantoin and cephalosporins; however, trimethoprim and co trimoxazole should be avoided in the first trimester, and fluoroquinolones (such as ciprofloxacin) are contraindicated. For patients diagnosed with acute pyelonephritis, initial treatment should be given in the hospital if the patient is vomiting (in which case, gentamicin is a reasonable first choice for drug therapy). The same drugs are used as in cystitis, but for 10 to 14 days. 1 figure. 2 tables. 12 references.

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Management of Urinary Tract Infections in Pregnancy Source: Journal of Perinatal and Neonatal Nursing. 8(1): 1-11. June 1994. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, P.O. Box 990, Frederick, MD 21701-9782. (800) 638-8437. Fax (301) 695-7931. Summary: Urinary tract infections (UTIs) are one of the most frequent complications of pregnancy. This clinical article presents information on the etiology, incidence, diagnosis, and management of asymptomatic bacteriuria and cystitis. The author notes that, when the lower UTIs of asymptomatic bacteriuria and cystitis are not eradicated, the subsequent risk of the development of pyelonephritis is increased. The associated decreased maternal morbidity and fetal prematurity are the goals of a screening and treatment program for pregnant women. Other topics covered include urinary tract changes during pregnancy; screening programs for UTIs; the symptomatology of cystitis; treatment recommendations; the long-term effects of UTIs; and drugs to avoid

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when UTI occurs during pregnancy. Nursing implications regarding patient education are also discussed. 1 figure. 3 tables. 17 references. (AA-M). •

Dynamic Interactions Between Host and Pathogen During Acute Urinary Tract Infections Source: Urology. 57(6A Supplement): 56-61. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: Urinary tract infections (UTIs) have traditionally been viewed as acute and often self-limiting infections caused predominantly by noninvasive Escherichia coli. However, this concept has been challenged by recent findings demonstrating that an acute bladder infection results from a complex series of host-pathogen interactions that can lead to bacterial invasion and persistence and that ultimately can determine the course of the infectious disease. This article reviews the dynamic interactions between host and pathogen during acute UTIs. The ability of E. coli to gain a foothold in the bladder is greatly facilitated by type 1 pilus-mediated attachment to and invasion of bladder epithelial cells. Invasion allows uropathogenic strains of E. coli to exploit the intracellular environment by replicating within these epithelial cells while evading a multitude of host defenses. An intracellular location also provides them a safe haven from many common antibiotic therapies. However, attachment and invasion also activates a cascade of innate host defenses, leading to the death and exfoliation of bladder cells and the production of inflammatory mediators. The ability of uropathogenic E. coli to flux out of cells and colonize surrounding cells provides them a mechanism to subvert these defense mechanisms and persist in the bladder epithelium for weeks following the acute infection. The authors conclude that the persistence of E. coli in bladder tissue may be relevant to more chronic diseases of the urinary tract such as recurrent UTIs and interstitial cystitis (IC). 1 figure. 29 references.

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Epidemiology of Interstitial Cystitis: Is It Time to Expand Our Definition? Source: Urology. 57(6 Supplement 1): 95-99. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: Very few epidemiological studies of interstitial cystitis (IC) have been published over the past 5 years. This article briefly reviews the significant findings from recent epidemiological studies of IC; considers how the study of a more inclusive clinical diagnosis termed chronic pelvic pain of bladder origin (CPPB) may further insights into this symptom complex, especially among men, various racial and ethnic minority populations, and children; and reviews the emerging literature dealing with the epidemiology of chronic pelvic pain. The criteria used to assist in identifying patients with IC have proven to be cumbersome and too restrictive. Other obstacles include the relative infrequency of IC, the long duration between development of symptoms and diagnosis; and the perception that the disorder occurs predominantly in white women. Evidence suggests that men with the IC symptom complex are often misdiagnosed by physicians and identified as having chronic prostatitis or benign prostatic hyperplasia. Children who present with the IC symptom complex are often thought to have voiding dysfunction. The authors propose that the more inclusive term CPPB be used in future epidemiological studies of persons with the characteristic IC symptoms of urinary frequency, urgency, and pain. Early studies of chronic pelvic pain in general suggest that it is most common in women, of unknown etiology (cause), and,

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in many patients, is associated with urinary bladder symptoms. The authors also describe a new research initiative from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) designed to establish a collaborative group of investigators focusing on better understanding the epidemiology of IC and CPPB. 32 references.

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

Project Title: 153 SM-EDTMP FOR BONE METASTASES--PHASE I DOSE ESCALATION STUDY Principal Investigator & Institution: Anderson, Peter; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001 Summary: The purpose of this study is to learn the dose of the investigational drug 153Sm-EDTMP that can be given to patients with cancer or those whom have not responded to therapy with surgery and chemotherapy. The study will also evaluate the side effects of this drug. 153Sm-EDTMP was eliminated relatively quickly after each infusion with uptake remaining in metastases or skeleton only by 24 hr. Bladder toxicity has not occurred. We are currently using IV hydration as the only means of cystitis prevention. Total body radiation levels on day 13 have been consistently very low, well below 1 mRem/hr at 1 meter safety limit. All patients have had stem cells infused 14 days after high dose 153Sm-EDTMP. Stem cell infusions have been given as outpatient observation with side effects limited to those usually associated with DMSO cryopreservative (temporary nausea, anorexia for 4-6 hrs). All patients have become temporarily pancytopenic after 153Sm-EDTMP. Once ANC is less than 500, patients have been provided with G-CSF to speed neutrophil recovery. Platelet transfusion requirements have been variable. Most patients have required only 1-3 platelet transfusions for platelet counts <20,000. Some but not all patients have also been transfused with packet red blood cells. Recovery of neutrophil count has generally occurred before day 14. No serious infections have been documented. Only 1 patient out

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

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of 8 has had a hospital admission associated with fever and antibiotic administration during neutropenia. The fever was probably catheter related and resolved with catheter removal. Since all patients have recovered from hematopoietic toxicity within 30 days, stem cell support successfully ameliorated hematopoietic toxicity in all patients treated with high dose 153Sm-EDTMP. Furthermore, since no serious non-hematologic toxicities have been seen, stem cell infusion offers promise of a means to escalate doses of 153Sm-EDTMP to even higher levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A CASE CONTROL STUDY OF INTERSTITIAL CYSTITIS Principal Investigator & Institution: Warren, John W.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Interstitial cystitis (IC) is a chronic bladder disease manifested by severe bladder pain and urinary frequency and urgency. Using criteria established by the NIDDK, the diagnosis can be made by objective visible findings at cystoscopy. However, IC remains a disease of unknown etiology, inconvenient diagnosis, and unclear natural history. Women comprise 90% of IC cases for unknown reasons. Patients report less life satisfaction than those with end stage renal disease. Identification of risk factors is a proven method for providing clues to pathogenesis of a disease, yet a properly designed study of IC with incident cases, appropriate controls, and attention to disease onset date has never boon performed. Herein we propose such a study comprising national samples of incident IC cases and age and gender matched controls with rigorous attention to onset dates of symptoms. By telephone interview and medical record review, we will identify risk factors for IC and reveal non-bladder syndromes associated with IC. In this group of recent onset cases where a convenient diagnostic test would be most useful, we will test the utility of antiproliferative factor, a urinary factor discovered by Susan Keay of our group. We propose then to follow this well-investigated cohort of IC cases to initiate a natural history study of the disease. This project will allow us to test several hypotheses: 1. That certain features that precede onset of IC symptoms, e.g., bacterial cystitis, distinguish IC cases from controls matched for age and gender, and may be risk factors for the disease. 2) That patients with IC have higher prevalences of certain non-bladder syndromes, e.g., irritable bowel syndrome, than do matched controls. 3) That urine APF, HB-EGF, and/or EGF are sensitive and specific diagnostic markers for IC in patients with symptoms of <=12 months. 4) That patients with IC have remissions and that certain clinical features, e.g., bacterial cystitis at disease onset, are prognostic factors for remissions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADRENOCEPTOR FUNCTION IN CATS WITH INTERSTITIAL CYSTITIS Principal Investigator & Institution: Westropp, Jodi L.; Veterinary Clinical Sciences; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-FEB-2001 Summary: Both cats and humans with interstitial cystitis (IC) have exacerbation of clinical signs during stressful periods. Based on previous studies, it is hypothesized that IC cats have a downregulation of their alpha-2 adrenoceptors (alpha2-AR), probably mediated by an increase in norepinephrine (NE). Stress can increase NE release and downregulate alpha2-AR, suppressing their ability to block painful input from the

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bladder sensory neurons. Autoradiography will be utilized to evaluate alpha2-AR in the bladder trigone and urethra as well as the locus coeruleus in both healthy and affected cats. Twenty four hour urine NE and cerebral spinal fluid will also be analyzed in both populations. Guanfacine, an alpha2-AR agonist, has been shown to decrease plasma norepinephrine. It will be used to assess inhibition of sympathetic outflow on functional sensitivity and anatomic density of alpha2-AR. Urethral and bladder strips from IC cats and healthy cats will be obtained to determine the effect of guanfacine on receptor function in vitro. These studies may prove beneficial in determining the appropriate therapy for clinical signs of IC in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AFFERENT MECHANISMS UNDERLYING BLADDER PAIN Principal Investigator & Institution: De Groat, William C.; Professor; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 28-FEB-2005 Summary: (adapted from applicant's abstract): Electrophysiologic, pharmacologic and neurochemical techniques will be used to examine the mechanisms underlying the neural detection of noxious stimuli in the lower urinary tract. The investigators are particularly interested in identifying the chemical mediators which sensitize bladder nociceptors and how these chemical mediators alter ion channels in afferent neurons and thereby change afferent receptor excitability. They will also examine changes in afferent neurons induced by chronic pathological conditions that result in bladder irritation and hyperactivity. Several hypotheses will be tested: (1) Several subtypes of nociceptors are present in the bladder wall and these subtypes exhibit distinct electrophysiologic properties and distinct receptive/signaling mechanisms, (2) Acute sensitization of bladder nociceptors involves a change in several membrane ion channels including: tetrodotoxin-resistant Na+ channels, vanilloid receptors (VRI) which are sensitive to capsaicin, ATP-sensitive purinergic receptors, fast activation K+ channels and acid sensitive caution channels (ASIC), (3) Chronic pathological conditions of the lower urinary tract alter the expression of ion channels or neurotransmitter mechanisms in afferent neurons. This effect may be mediated by neurotrophic factors released within the bladder; (4) Bidirectional chemical communication between the urothelium and adjacent nerves plays a role in sensory mechanisms as well as in epithelial cell function in the urinary tract. The long-term objectives of the research program are to understand the mechanisms by which irritating or tissue-injuring stimuli are detected and processed by the nervous system and in turn modulate urinary tract function. The contribution of the urothelium to sensory processing will receive particular attention. The ultimate goal is to identify new molecular targets for drug therapy of bladder pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AFFERENT PLASTICITY UNDERLYING URETHRAL AND PELVIC PA Principal Investigator & Institution: Yoshimura, Naoki; Associate Professor; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Patients with painful bladder syndromes such as interstitial cystitis (IC) characterized by urinary frequency, urgency, and bladder pain often exhibit urethral or pelvic pain. It is also documented that peripheral nerve injury in the pelvis may

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contribute to the emergence of bladder and/or pelvic pain because surgical manipulation of visceral organs is known to be a risk factor for the IC, and also often leads to aggravation of existing symptoms or onset of new symptoms in patients with pelvic pain. The urethra, urethral sphincter muscles and the pelvic floor are innervated by a subset of visceral (pelvic and hypogastric) and somatic (pudendal) afferent fibers which are a more diverse population (C, Asigma and Abeta-fibers; possibly Aalphafibers) than those innervating the urinary bladder (C and Asigma-fibers). However, little is known about their functional characteristics and changes under chronic pathological conditions including tissue inflammation or nerve injury that may result in chronic urethral or pelvic pain. Thus, in this research project, electrophysiologic, pharmacologic, molecular and neurochemical techniques will be used to examine the characteristics of urethral afferent neurons and somatic afferent neurons in the pudendal nerve. We are particularly interested in characterizing membrane properties of these afferent neurons, and also in identifying how the chemical mediators or pathology alter ion channel and receptor properties, leading to neuronal hyperexcitability. Several hypotheses will be tested: (1) Multiple subtypes of afferent neurons can be identified based on their functional and morphological properties including tetrodotoxin-resistant Na+ channels, slow-inactivating transient K+ channels, vanilloid receptors (VR1) sensitive to capsaicin, and immunoreactivity against specific cellular markers such as neurofilament or isolectin-B4, (2) Chronic inflammation of the urethra/pelvic floor or direct injury to the pudendal nerve alters the expression of ion channels or neurotransmitter mechanisms in afferent neurons, resulting in hyperexcitability of these neurons. These changes might be different from those that we have been recently identified in bladder afferent neurons, (3) Functional changes in urethral afferent neurons or pudendal afferent neurons under chronic pathological conditions can induce bladder and/or urethral hyperactivities by reorganizing viscerosomatic reflex activities. The long-term objectives of the research program are to understand the mechanisms by which irritating or nerve-injuring stimuli in pelvic organs induce phenotypic changes in their afferent pathways and thereby trigger chronic pain in the pelvis. If a specific relation is found between different pathology and alteration in ion channel or receptor properties/expression, it is possible to identify new molecular target of drug therapy for chronic bladder and/or pelvic pain associated with painful bladder syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AN IN VITRO MODEL FOR EVALUATION OF IC THERAPIES Principal Investigator & Institution: Mundel, Peter; Associate Professor; Medicine; Yeshiva University 500 W 185th St New York, NY 10033 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The purpose of this study is to create conditionally immortalized human urothelial cell lines that retain key differentiated features of the highly specialized urothelium. This model will eliminate the need for unpredictable, short-lived primary cultures obtained from human subjects, and provide a consistent and self-renewing resource for the objective evaluation of current and future treatments for interstitial cystitis. When the cell line is established, we will determine how intravesical treatments (which are thought to restore the protective glycosaminoglycan layer) affect urothelial function. This will be the first objective evaluation of these empiric treatments. We will also evaluate potential diagnostic urinary markers for IC. Immortalized cell culture lines. We will first establish primary cultures from human cystoscopic biopsy specimens. These cell lines will be immortalized with a retroviral construct containing a thermosensitive version of the SV40 large-T antigen. This will

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allow the urothelial cells to proliferate indefinitely, providing a reliable supply of cells. Urothelial differentiation can be induced by thermoshift to nonpermissive culture conditions. A model for the urothelium in IC. Disruption of the cultured urothelium with protamine sulfate creates a state similar to interstitial cystitis. Evaluation of intravesical therapies. Heparin and hyaluronic acid are currently thought to restore the glyosaminoglycan layer that protects the urothelium, but this has never been proven. The urothelium will be disrupted, and the urothelial function will be assessed. Heparin or hyaluronic acid will be instilled into the culture media (similar to the way they are applied in the bladder), and the same parameters will be measured after treatment. Evaluation of urinary markers. The cellular effects of antiproliferative factor and glycoprotein 51 will also be evaluated. In summary, treatments for interstitial cystitis have been difficult to evaluate because of the lack of a reliable cell culture model, and many therapies are used empirically. An immortalized cell culture line will enable us to directly evaluate current therapies, and facilitate the development of novel treatments for interstitial cystitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APPLIED METHODS FOR ANALYSIS OF INTERSTITIAL CYSTITIS Principal Investigator & Institution: Propert, Kathleen J.; Associate Professor; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (Adapted from the Applicant's Abstract): Interstitial cystitis (IC) is a chronic syndrome of the urinary bladder that primarily affects women. A broad clinical definition of IC includes any patient who complains of pelvic/perineal pain, urinary urgency, or voiding frequency in absence of any obvious cause such as infection or cancer. In 1993, the NIDDK established the Interstitial Cystitis Data Base (ICDB) as the first prospective longitudinal cohort study of patients with symptoms consistent with IC. The enrolled 637 patients diagnosed with IC and followed them for up to four years. Baseline measures included demographics, medical history, detailed symptom questionnaires, and urodynamic testing. Cytoscopy/hydrodistention and bladder biopsies were performed at the discretion of the treating physician. The proposed research involves targeted analyses using the ICDB to address clinically and scientifically relevant questions regarding the natural treated history of IC. This can provide insight into the epidemiology and etiology of IC, aid in the refinement of diagnostic criteria, and ideally identify groups to which specific treatment modalities may be targeted. There are three goals of the proposed research. The first is to identify subgroups of patients with IC characterized by constellations of symptoms, lifestyle factors, and/or biological markers. These analyses will involve both cross-sectional (baseline) and longitudinal comparisons between symptom severity and demographics, comorbidities, seleceted therapies, and cystometric measures. Detailed statisticall analyses of pathological features derived from bladder biopsies and their association with symptoms will be performed. The second goal is to conduct exploratory analyses of various outcome measures, both cross-sectionally and longitudinally, to provide guidelines for the design, conduct, and analysis of future clinical trials in IC. These analyses will include the evaluation of quality of life over time and the exploration of various definitions of response derived from longitudinal symptom changes. The third goal relates to the application and/or development of statistical methodology to aid in the identification of subgroups and evaluation of outcome measures. The methodology includes latent variable modeling of multiple outcome data, methods for tracking of

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symptoms in multiple domains over time, methods for assessing regression to the mean, and risk-set matching for evaluation of time-dependent treatment decisions. In addition, through this project, the ICDB will be maintained and made available to external investigators interested in using the data to explore specific hypotheses related to the natural history of IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASSESSING REGRESSION TO THE MEAN & INTERVENTION EFFECT Principal Investigator & Institution: Lin, Hung-Mo; Health Evaluation Sciences; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 30-JUN-2003 Summary: The proposed research is designed to contribute to an understanding of the impact and implications of the regression to the mean (RTM) effect in health research and to provide some statistical solutions to the RTM effects when assessing the effectiveness of the intervention on marker value(s) obtained at or prior to screening. RTM means that when repeated measurements of a variable are taken for a nonrandomly selected subgroup, the average of the subsequent measurements will tend to move toward the population mean. The bias introduced by RTM can be encountered in practically every type of health study. Therefore, the results of this research will provide a valuable contribution to a broad spectrum of health research. This application will focus on analyzing the change in event probability resulting from the implementation of an intervention among a selected sub-population when the event of interest postselection is a binary outcome. The marker used in selection might be the same as the outcome variable or it might be a continuous variable believed to reflect the likelihood of the outcome. The methods will be applied to real data sets from NIDDK interstitial cystitis observational study and the Pennsylvania Health Care Cost Containment Council (HC4) Reports. The proposed research is innovative and significant because current available methods for adjustment for RTM have focused only on data that are normally distributed, which are no longer adequate to cope with the complexities of health services outcomes and clinical studies in the real world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BACTERIAL INTERACTIONS WITH THE BLADDER MUCOSA Principal Investigator & Institution: Mulvey, Matthew A.; Pathology; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (adapted from application abstract): This is a study of host- pathogen interactions at the molecular level, specifically the structural functional relationship of bacterial attachment to host epithelial cells. Urinary tract infections (UTIs) affect a large proportion of the world population and account for significant morbidity and high medical costs. Escherichia coli is the etiologic agent in the majority of all UTIs, including cyctitis. Other members of the Enterobacteriaceae family, including Klebsiella species and Proteus mitabilis, and Gram-positive organisms, including Staphylococcus saprophyticus and opportunistic enterococci species, are also associated with UTIs. To act as pathogens, these various bacteria must first adhere to host mucosal surfaces within the urinary tract. Without the ability to specifically adhere to host tissues, these pathogens would be readily expelled from the host and disease would not occur. Bacterial attachment can initiate a cascade of molecular crosstalk between bacterial and

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host cells that can directly influence the course of an infection. Virtually all uropathogenic strains of E. coli and most members of the Enterobacteriaceae family encode filamentous surface adhesive organelles called type 1 pili. These structures can mediate bacterial attachment to bladder epithelial cells by interacting with host receptor complexes comprised of integral membrane proteins known as uroplakins. The candidate proposes to use type 1-piliated uropathogenic E. coli as a model to study the structural basis of bacterial attachment and the functional consequences of the attachment event. The specifics of the interactions between type 1 pili and uroplakin receptor complexes will be examined. In addition, the bacterial and host factors that come into play as a consequence of bacterial adherence and influence the pathogenesis of UTIs will be analyzed at both the cellular and molecular level. This work will lead to enhanced understanding of pathogenic processes both within the urinary tract and at other sites of microbial entry and will facilitate the development of novel antimicrobial therapeutics and vaccines. The specific aims are to: 1.Characterize interactions between type 1 pili and the uroplakin receptor complexes that coat the lumenal surface of the bladder. Mutational analysis of recombinant uroplakin protein complexes and of type 1 pili along with biochemical, microscopic, and crystallographic techniques will provide detailed insight into the host-pathogen interactions involved in the establishment of UTIs by uropathogenic E. coli. 2.Investigate virulence factors and mechanisms that enable uropathogenic E. coli to invade, disseminate, and persist within the bladder following the initial attachment event mediated by type 1 pili. The possibility that recurrent UTIs may, in some cases, be a manifestation of a lingering chronic infection will be tested. 3.Elucidate host responses to uropathogenic E. coli, including the identification and characterization of innate and adaptive host defenses that function to limit and clear invading bacteria from the urinary tract. Cell culture systems and a murine cystitis model will be used to delineate vital constituents of an effective host response to infection by type 1-piliated E. coli. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BCG IN ENDOGENEOUS AND EXOGENOUS ANTIGEN-INDUCED T CELL Principal Investigator & Institution: Luo, Yi; Urology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): The purpose of this project is to create antigeninduced T helper (Th) polarized bladder inflammation models to mimic the postulated pathogenesis of interstitial cystitis (IC) and investigate the potential effect of the Bacillus Calmette-Guerin (BCG) vaccine on treating the disease in these models. The long-term goal is to develop effective treatment strategies to combat IC. Towards achieving these goals, three specific aims will be undertaken: Specific Aim 1: To create an exogenous antigen-induced bladder inflammation model to determine the role of systemic Thl and Th2 immune polarization in the development of bladder inflammation. To create this model, T helper cells will be isolated from transgenic mice (termed OT-II) that express Th cells specific for the ovalbumin (OVA) antigen. These Th cells will be differentiated in the laboratory into Thl or Th2 subsets, and adoptively transferred into genetically compatible mice. Cystitis will be induced in the recipient mice by instilling OVA directly into the bladder. This model will particularly lend itself to studies on acute inflammation. Specific Aim 2. To establish a bladder autoimmune disease model by creating a novel transgenic mouse strain that expresses OVA as a "self" antigen via promoter-specific production by the urothelium and to determine the role of the Th

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immune polarization in the development of this disease. This transgenic mouse strain (termed URO-OVA) will be genetically engineered with DNA containing a bladderspecific promoter and the gene for OVA. An autoimmune form of cystitis will be developed in these URO-OVA mice by adoptive transfer of polarized OT-II Th cells. This model particularly lends itself to studies on chronic inflammation. Specific Aim 3. To assess the therapeutic effect of BCG in antigen-induced bladder inflammation. BCG will be evaluated for its effect on treating Th2 polarized cystitis (the hypothesized type responsible for IC) in both exogenous and endogenous antigen-induced cystitis models. BCG is predicted to shift the diseased Th2 immune state back to a favorable Th1 state. Successful completion of this study will establish the pathological and immunological characteristics for both Th1 and Th2 type cystitis, shed light on BCG's effect on treating this disease, and aid in the future development of prevention and treatment strategies for IC and other painful bladder conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEAUMONT/FORD INTERSTITIAL CYSTITIS CLINICAL CENTER Principal Investigator & Institution: Diokno, Ananias C.; Professor and Chief; William Beaumont Hospital 3601 W Thirteen Mile Rd Royal Oak, Mi 480736769 Timing: Fiscal Year 2001; Project Start 29-JUN-1998; Project End 28-FEB-2003 Summary: (Abstract of the application) The objectives of the Beaumont/Henry Ford interstitial cystitis (IC) clinical center are (1) to provide an experienced clinical center that will collaborate with the other IC centers and the data coordinating center to conduct clinical trials for treating patients with IC, (2) to conduct a prospective randomized placebo controlled trial comparing intravesical BCG in patients with IC pretreated with intravesical pentosan Polysulfate (PPS) or placebo, (3) to perform a preliminary (pilot) study to reinduce IC patients who failed the initial intravesical BCG therapy with a second induction of intravesical BCG. The first clinical trial will test the hypothesis that pretreatment of the bladder with intravesical PPS prior to instillation of BCG will increase the response rate compared to intravesical BCG alone. The enhancing effect of PPS on intravesical BCG treatment is believed to be due to strong attachment of BC to PPS, which binds tightly to the bladder mucosal lining. By increasing the binding of BCG to the bladder, we hypothesize that the immunologic effect of BCG may be enhanced. The second clinical trail will test the hypothesis that re-induction of intravesical BCG therapy to BCG non-responders will convert 50 of these to responders, similar to the response rate of carcinoma-in-situ patients who receive a reinduction BCG therapy. It is assumed that the second therapy will enhance the initial immunity conferred to these non-responders. The Beaumont/Henry Ford center will provide the NIH trial group a team of investigators experienced in clinical collaborative research as they have been part of the IC Data Base with a proven record of successful recruitment and retention of IC subjects. The team has expertise in clinical trials specifically in the use of BCG in the treatment of IC. If the proposed trials prove to be successful, we will be armed with a highly effective and durable treatment for IC. The combination therapy will also potentially reduce the dos of BCG, which will lower the cost and decrease the potential morbidity of this treatment program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BECOMING A MEMBER OF THE CPCRN-FOR PROSTATITIS Principal Investigator & Institution: Berger, Richard E.; Associate Professor; Urology; University of Washington Seattle, Wa 98195

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Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The long-term goals of the proposal are to establish a clinical center for the study and treatment of chronic pelvic pain in both genders and to co-operate with and contribute to other investigators in establishing and conducting multicenter clinical trials. In specific, this proposal is concerned with men with chronic male pelvic pain syndrome and with becoming a clinical site for the CPCRN. Our specific aims are to: (1) assist the CPCRN to establish study designs for clinical trials, develop forms, develop clinical definitions, recruit subjects for CPCRN trials, and to analyze and publish data in a co-operative and interactive manner; (2) support and take part in the Urological Chronic Pelvic Pain Syndromes Collaborative Group in a cooperative and interactive manner; (3) develop and conduct ancillary studies, which will provide further understanding of chronic prostatitis. Subjects will be recruited from the practice of Dr. Berger at the University of Washington Medical Center (UWMC) and the outpatient clinics at Group Health Cooperative of Puget Sound (GHC) and the University of Washington Physicians Network (UWPN). Dr. Berger sees approximately 200 new patients with CPPS per year, and GHC sees approximately 250 patients per year with newly diagnosed CPPS. By combining the patient population of both Seattle Medical Centers, we will be able to recruit a mix of previously treated and newly diagnosed patients into CPCRN clinical protocols. The Principal Investigator has a multidisciplinary team, currently performing clinical and laboratory studies in CPPS in men. Over the past four years, the Principal Investigator has enrolled 590 subjects into IRB approved studies of CPPS that have used a variety of methodological perspectives and examined a variety of etiological factors. We believe that we are ideally suited to contribute to the design and implementation of future studies performed by the CPCRN. Furthermore, the same multidisciplinary focus and experience will allow us the flexibility to design and carry out ancillary studies, which will fit with the overall plan of the CPCRN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLADDER GLYCOSPHINGOLIPIDS IN THE PATHOGENESIS OF URINARY TRACT INFECTION Principal Investigator & Institution: Stapleton, Ann E.; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001 Summary: Although the bladder is by far the most common site of UTI, little is known about the molecules to which infecting bacteria attach in this tissue as compared with the kidney, in which the role of globoseries GSLs as bacterial attachment sites for Escherichia coli has been well studied. Since the carbohydrate portion of GSLs varies in different tissues, often under host genetic control, these molecules serve as determinants of both patient susceptibility to infection and tissue tropism for pathogenic bacteria. The overall goal of this proposal is to utilize primary cell cultures from the bladder as a model system to define the role and regulation of bladder GSLs as attachment sites for uropathogenic bacteria, focusing on the two most common causes of cystitis in women, E. coli and S. saprophyticus, in the following proposed studies: (1) To evaluate the hypothesis that globoseries (Gb) and ganglioseries (Gg) GSLs are present in primary cultures of bladder transitional epithelium and bind E. coli and S. saprophyticus, respectively, we will purify GSLs from the cells, identify E. coli-and S. saprophyticusbinding GSLs, and confirm the identities of the GSLs using specific monoclonal antibodies (MAbs) and formal carbohydrate structural analysis; (2) To evaluate the hypothesis that the GSLs identified in Specific Aim 1 are surface exposed in primary

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bladder cell cultures and are functionally relevant in E. coli and S. saprophyticus attachment, we will study bacterial adherence before and after pre-treatment of the cell cultures with an saprophyticus attachment, we will study bacterial adherence before and after pre-treatment of the cell cultures with an inhibitor of GSL synthesis or MAbs directed against relevant GSLs; (3) To evaluate the hypothesis that the secretor and ABO genes influence the expression of Gb and Gb GSLs in the bladder and thus the capacity for E. coli binding, we will establish primary bladder cultures from patients of known secretor/ABO status and determine whether the predicted glycosyltransferases and GSL products are present in the cultured cells; and (4) To evaluate the hypothesis that cytokines are release from primary uroepithelial cell cultures and modulate the expression of E.coli-and S. saprophyticus-binding GSLs in the bladder, we will to examine the effects of adherence by E. coli and S. saprophyticus on cytokine release from the cells and the effects of tumor necrosis factor and IL-1, IL-6 and IL-8 on the expression of relevant GSLs in primary urothelial cell cultures and on bacterial adherence to these cells. These studies on the expression and regulation of bladder GSLs are relevant to the pathogenesis of infection, inflammation and differentiation in this organ and could eventually lead to novel approaches to prevention of bacterial attachment and infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BOTULINUM CYSTITIS/CHRON*

TOXIN

THERAPY

FOR

INTERSTITIAL

Principal Investigator & Institution: Fitzgerald, Mary P.; Assistant Professor; Obstetrics and Gynecology; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The Loyola Female Pelvic Medicine team proposes to participate in the Interstitial Cystitis/Chronic Pelvic Pain (IC/CPP) Clinical Trials Network in order to advance the understanding of the clinical care of women with these complex disorders. Our multidisciplinary team has the clinical volume and proven ability to participate in development of cooperative studies and to recruit to finally approved protocols. As a referral center for IC/CPP in the Chicago area, we believe our participation will benefit the network by bringing a large patient base and a long clinical experience to the group, and will benefit our patients by making state-of-the-art treatments available to them. As requested in the RFA, we offer a concept protocol which studies the use of botulinum toxin injection into either detrusor or pelvic floor musculature, for the treatment of IC/CPP. The Loyola team: Understands the significance of this important treatment network, Can recruit and retain patients of racial, economic and ethnic diversity, Has experienced investigators including physicians, nurses, physical therapist and urodynamic technicians, Has a current clinical practice which offers surgical, pharmacological and behavioral treatment for IC/CPP, Can ensure data management and transmission, and Looks forward to cooperation with the other treatment centers in order to maximize the benefits of this treatment network for our patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CD11B/CD18 AND NEUTROPHIL EPITHELIAL INTERACTIONS Principal Investigator & Institution: Parkos, Charles A.; Associate Professor, Director; Pathology; Emory University 1784 North Decatur Road Atlanta, Ga 30322

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Timing: Fiscal Year 2001; Project Start 05-APR-1995; Project End 29-FEB-2004 Summary: Many inflammatory diseases of mucosal surfaces are characterized by transepithelial migration of neutrophils (PMN). Examples of such diseases are common in the gastrointestinal system (ulcerative colitis, Crohn's disease), respiratory tract (bronchial pneumonia, bronchitis), and urinary tract (pyelonephritis, cystitis). Accumulation of neutrophils within the lumenal spaces of these organs is associated with epithelial injury and correlates with disease symptoms. Despite a wealth of evidence supporting a central role of PMN in epithelial dysfunction in these diseases, the mechanism(s) of leukocyte interaction with mucosal remains poorly defined. In this proposal, our studies will focus on defining the molecular basis of leukocyte interactions with epithelial cells. Previously, we have shown that PMN transepithelial migration requires specific regions of the neutrophil beta2 integrin CD11b/CD18 and is independent of selectins and ICAM-1. Furthermore, we identified CD47 as an additional crucial component of the transepithelial migration response. However, the precise molecular details of these adhesive events and the nature of the epithelial counterreceptors for migrating PMN remain undefined. The overall goals of this proposal are to identify and characterize key adhesive interactions between neutrophils (PMN) and epithelial cells that serve to regulate the process of PMN transepithelial migration. Recently, a novel immunoglobulin superfamily member termed junction adhesion molecule (JAM) that is concentrated at cell-to-cell borders (intercellular junctions) of murine endothelium and epithelium was shown to participate in monocyte transmigration across mouse endothelium. In Specific Aim 1, we will extend our primary characterizing of the human homolog of JAM to define its role in PMN interactions with epithelial cells. In Specific aim 2, we will define the mechanism of how a novel epithelial mAb inhibits PMN migration and continue to produce others that inhibit the PMN transmigration response. Specific aim 3 will focus on the identification of specific epithelial receptors for CD11b/CD18 using monoclonal antibodies. Lastly, Specific aim 4 will employ random peptide phage display to identify peptide ligands for CFD11b/CD18 that modulate PMN-epithelial adhesion, Information from these studies will lead to a better understanding of the molecular events involved in PMN interactions with epithelial cells and may provide new ideas for therapeutic strategies aimed at attenuating inflammatory diseases of mucosal surfaces. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMICAL INDUCED NEPHROTOXICITY--SUCCINIMIDES Principal Investigator & Institution: Rankin, Gary O.; Professor and Chair; Pharmacology; Marshall University Huntington, Wv 25701 Timing: Fiscal Year 2001; Project Start 01-APR-1983; Project End 31-MAR-2003 Summary: Several succininimide derivatives have been shown to induce renal damage (acute tubular necrosis, interstitial fibrosis) or bladder damage (hemorrhagic cystitis) in man and/or animals. The wide use of succinimide compounds with little understanding of the mechanisms by which this class of compounds can induce nephrotoxicity and bladder damage, indicates the need for mechanistic studies of succinimide- induced toxicity. This proposal will continue our studies to investigate the mechanism(s) of Nand C-arylsuccinimide-induced nephrotoxicity and urotoxicity. For N-arylsuccinimides, we will test the hypothesis that N-arylsuccinimides are biotransformed in the liver to sulfate and glucuronide conjugates which are carried by the blood to kidney where they accumulate. The conjugates then either release N-aryl maleimides which can alkylate renal macromolecules (e.g. mitochondrial proteins) or directly alkylate/acylate similar cellular targets. This hypothesis will be examined in four specific aims using the

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agricultural fungicide N- (3,5-dichlorophenyl) succinimide (NDPS) as the parent succinimide. In Aim 1 we will identify the nephrotoxicant conjugate(s) of NDPS using in vivo and in vitro models. Aim 2 will examine the cellular mechanism of NDPS nephrotoxicity (effects on cell calcium, ATP production oxygen consumption) using isolated renal proximal tubule epithelial cells and isolated renal cortical mitochondria. In Aim 3, we will investigate renal cellular localization and potential cellular targets for NDPS using immunohistochemical and immunochemical techniques to complement studies in Aims 1 and 2, while in Aim 4 we will begin to investigate how toxic NDPS metabolites enter target tissue using primary cultures of rat renal proximal tubular cells grown on permeable supports. C-Arylcuccinimide urotoxicity also is postulated to occur following conversion of the succinimide to reactive species (i.e. maleimides). Using the antiepiletic agent phensuximide (PSX) as our prototypic succinimide, in Aim 5 we will investigate (a) which PSX metabolites are urotoxicants (b) if PSX is biotransformed to a maleimide metabolite and (c) the ability of MESNA to attenuate PSX urotoxicity. Collectively, the results of these studies should add important, new knowledge about the nephrotoxic and urotoxic species of succinimides, cellular targets of the toxicant species and potential mechanisms of nephrotoxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHRONIC PROSTATITIS COLLABORATIVE CLINICAL STUDIES Principal Investigator & Institution: Alexander, Richard B.; Professor; Surgery; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): Chronic prostatitis/chronic pelvic pain syndrome is a common but poorly understood condition affecting men of all ages. Infection has dominated the thinking about this disease for decades. However, a growing body of evidence provides significant challenge to the notion that infection contributes to symptoms in a significant proportion of patients. Much of this new information was developed by the Chronic Prostatitis Collaborative Research Network (CPCRN), a six year project representing the first NIH-funded collaborative study of chronic prostatitis. The long-term goal of this application is the continuation of our involvement in the Chronic Prostatitis Collaborative Research Network. In addition, we will collaborate with investigators studying interstitial cystitis under an umbrella group, the Urological Chronic Pelvic Pain Syndromes Collaborative Group. We describe the activities at our center over the past 7 years in the study of chronic prostatitis/chronic pelvic pain syndrome and describe the clinical and research infrastructure and expertise that we propose to continue to apply to the study of chronic prostatitis/chronic pelvic pain syndrome as part of this cooperative group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHRONIC PROSTATITIS COLLABORATIVE CLINICAL TRIALS Principal Investigator & Institution: Mcnaughton-Collins, Mary F.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): This application reflects a proposal from the Brigham and Women's Hospital (BWH) and Massachusetts General Hospital (MGH) / Harvard Medical School to become one of the Clinical Centers of the Chronic Prostatitis Collaborative Research Network (CPCRN) to develop and conduct randomized clinical trials for evaluating novel therapies in patients with chronic prostatitis/chronic pelvic

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pain syndrome (CP/CPPS). The BWH/MGH Harvard clinical center has a history of successful recruitment and retention of CP/CPPS patients, including a substantial proportion of Latino patients, from the New England area for CPCRN 1997- 2003 - both for the Chronic Prostatitis Cohort Study and Randomized Clinical Trial. Drs. Mary McNaughton Collins and Michael O'Leary have advanced the field of CP/CPPS by helping to develop and validate the NIH-Chronic Prostatitis Symptom Index, translating the index to Spanish, evaluating the quality of life and resource utilization of men with CP/CPPS, as well as examining the epidemiology and natural history of the condition. Dr. McNaughton Collins has also performed several chronic prostatitis studies as a member of the Patient Outcomes Research Team (PORT) for Prostate Diseases and the Cochrane Collaboration. The BWH/MGH Harvard clinical center has expanded to include a multi-institutional and multi-disciplinary network of co-investigators and consultants with both content (i.e., chronic prostatitis, pain management) expertise and methodological (i.e., clinical trials, basic science, and outcomes research) training, as well as fresh sources of chronic prostatitis patients, especially newly diagnosed patients and minority patients. The new reservoirs of CP/CPPS patients include: 1) newly diagnosed CP/CPPS patients from primary care practices and medical walk-in units across the two large institutions and their neighborhood health centers, including the BWH internal medicine Spanish clinic; 2) both newly diagnosed and long-term CP/CPPS patients from the MGH Spanish urology clinic, and; 3) both newly diagnosed and long-term patients from Boston Medical Center, which is a large, inner-city academic health center providing care to a large proportion of African American patients. To assist in the recruitment and retention of Latino men, the site now includes 3 Spanish speaking medicine and urology investigators, and the Research Coordinator is taking Spanish classes to become proficient. This proposal includes a clinical trial design for consideration by the CPCRN. The multi-institutional, multi-disciplinary team from the BWH/MGH Harvard clinical center is eager to collaborate on treatment trials and ancillary studies with other CPCRN centers, the NIH/NIDDK scientific team, and the Interstitial Cystitis Clinical Trials Group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHRONIC PROSTATITIS COLLABORATIVE RESEARCH NETWORK Principal Investigator & Institution: Anderson, Rodney U.; Urology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): This application proposes that Stanford University School of Medicine, Department of Urology, participate as one of several National Clinical Centers in a cooperative effort to develop feasible clinical trials for the study of chronic prostatitis/chronic pelvic pain syndrome. The Principal Investigator intends to participate fully as a member of the steering committee in designing randomized controlled clinical trials and facilitate carrying them out in collaboration with other national center Pl's. The investigative group at Stanford will work in parallel with the centers conducting trials for investigation of interstitial cystitis. A simultaneous application for that effort is being submitted. While the precise pathophysiology and biologic basis of chronic pelvic pain, particularly associated with genitourinary dysfunction, have not been elucidated, a large number of men in the United States continue to suffer immeasurably for many years with this chronic disorder. Multimodal therapy exists as the only management approach and, for the most part, lacks sound scientific justification. The specific aim of this project is to utilize clinical experience from the most experienced and knowledgeable physicians available to design clinical trials of

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treatment modalities that may provide a favorable therapeutic response among the many sub-groups of this population of patients. Investigation within these trials will stretch from pharmaceutical to complimentary holistic treatment methods, representing the best of ideas chosen by the participating centers. The Stanford Group intends to contribute experience and expertise with regard to managing chronic prostatitis/chronic pelvic pain syndrome utilizing a neurobehavioral therapy and proposes a clinical trial of targeted physiotherapeutic myofascial release of painful trigger points with progressive relaxation exercises. The psychophysiological vagaries among patients suffering from this disorder have long been appreciated, but poorly defined, and deserve a fresh look with a dedicated "hands on" clinical effort conducted by several investigators simultaneously and with rigorous clinical research design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHRONIC PROSTATITIS COLLABORATIVE RESEARCH NETWORK Principal Investigator & Institution: Litwin, Mark S.; Associate Professor; Urology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The goal of this application is to establish a clinical trial center at UCLA, Harbor UCLA Medical Center, and Martin Luther King-Drew Medical Center that will participate in collaborative, multi-site clinical trials sponsored by a newly established NIDDK-sponsored Chronic Prostatitis Collaborative Research Network (CPCRN). As a CPCRN site, UCLA will (1) participate in the design of randomized controlled clinical trials to treat the symptoms associated with chronic prostatitis, also known as chronic pelvic pain syndrome (CPPS) (2) develop and conduct ancillary studies, which will provide further understanding of CPPS (3) determine if there is a different response to therapy between sub-groups of patients, including newly diagnosed and chronic, long-term patients with CPPS (4) recruit sufficient numbers of patients with CCPS, including an adequate number of newly diagnosed cases, into these clinical trials (5) jointly work with other CPCRN investigators, including a Data Coordinating Center, to analyze and interpret the results of the trials (6) participate in a newly established Urological Chronic Pelvic Pain Syndromes Collaborative Group to facilitate the efficient conduct of clinical trials in both interstitial cystitis and chronic prostatitis The study will develop a clinically relevant definition of the urologic chronic pelvic pain syndromes, based on the clinical findings from these and other related clinical studies. The UCLA site has demonstrated experience in recruiting minority subjects to participate in research studies, including clinical trials, for CPPS and other urologic conditions. The UCLA site will build upon its experience as a charter site in the first CPCRN to achieve the goals set out by the second. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL DEVELOPMENT OF 4-HYDROPEROXYIFOSFAMIDE Principal Investigator & Institution: Morgan, Lee Roy R.; Chief Executive Officer; DekkTec, Inc. 4200 Canal St, Ste a New Orleans, La 70119 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant): The objective of the proposed research is to synthesize 4-hydroperoxyifosfamide (HOO-IFOS) in sufficient quantity for evaluation in vivo against a human osteosarcoma xenograft and additional tumor xenografts of breast, lung (small cell and non-small cell) and ovary cancers. A cyclophosphamide-

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resistant human melanoma xenograft will also be used in order to determine the efficacy of this pre-activated form of the clinical antitumor drug ifosfamide (IFOS) in comparison with IFOS, cyclophosphamide (CPA) and 4-hydroperoxycyclophosphamide (4-HC) as a guide to possible further development of HOO-IFOS as a clinical anticancer agent. Plasma levels of chloroacetaldehyde, a metabolite of IFOS implicated as the causative agent in its neurotoxicity, and acrolein, the metabolite of IFOS and CPA that causes dose-limiting hemorrhagic cystitis, generated by HOO-IFOS vs. IFOS will be measured as an indication of comparative neurotoxic or hemorrhagic cystitic potential, resp. Possible clinical advantages of HOO-IFOS in comparison to IFOS or CPA are (1) elimination of variation in active drug administered to patients, (2) reduction or elimination of toxicities associated with IFOS or CPA and (3) possible reduction in CPArelated resistance. PROPOSED COMMERCIAL APPLICATIONS: It is possible that HOO-IFOS could become a superior clinical drug to CPA or IFOS for treating certain tumor types now treated with these two drus because of comparable/superior activity but with reduced toxicities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYSTITIS-INDUCED PLASTICITY OF MICTURITION REFLEXES Principal Investigator & Institution: Vizzard, Margaret A.; Associate Professor; Neurology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2003; Project Start 29-JUL-1996; Project End 30-JUN-2008 Summary: (provided by applicant): Interstitial cystitis (IC) is a chronic inflammatory bladder disease syndrome characterized by urinary frequency, urgency, suprapubic and pelvic pain. The working hypothesis for this proposal is that urinary bladder hyperreflexia and altered sensation that accompany IC are due to an alteration in the primary afferent limb of the micturition reflex and, in part, to an alteration in interneuronal mechanisms in the spinal cord. Urinary bladder hyperreflexia after cystitis may also be due to an alteration in the efferent limb of the micturition reflex. The combination of these changes facilitates a spinal reflex pathway to the urinary bladder by altering various types of synaptic transmission at the interneuronal level in the spinal cord and by altering synaptic transmission to the pelvic ganglia. The following aims address these hypotheses: 1). Previous studies have demonstrated significant increases in urinary bladder neurotrophic factor (NTF) mRNA/protein after chronic cyclophosphamide (CYP)-induced cystitis. Thus, the role that NTFs (eq., nerve growth factor, NGF; brain derived neurotrophic factor, BDNF) play in mediating, functional, neurochemical and organizational plasticity of bladder reflexes after cystitis will be examined by chronic administration of NTFs in vivo. The companion studies will examine the effects of administration of NTF neutralizing antibodies on this plasticity after cystitis. 2). Previous studies have demonstrated dramatic upregulation of the peptide, pituitary adenylate cyciase-activating polypeptide, (PACAP) in bladder afferent and spinal pathways after cystitis. We will extend these observations by examining the functional significance of this upregulation. Thus, the influence of PACAP antagonists on bladder reflexes will be determined. Furthermore, the role of PACAP in cystitis-induced bladder hyperreflexia will be examined in PACAP knockout mice. 3). In the current proposal, we will take a new approach by examining changes in the properties of an efferent component of micturition reflexes. Thus, the electrical and pharmacological properties of bladder postganglionic neurons after CYP-induced cystitis will be examined. These studies will involve, in vitro, intracellular recordings from the cell body of the postganglionic neuron located in the major pelvic ganglion.

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Axons of these neurons terminate in the inflamed urinary bladder and these cells are also likely to be influenced by the inflammatory milieu. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DCC--INTERSTITIAL CYSTITIS CLINICAL TRIALS GROUP Principal Investigator & Institution: Landis, J R.; Professor; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 10-MAY-1998; Project End 28-FEB-2003 Summary: (Abstract of the Application) This is an application from the Center for Clinical Epidemiology and Biostatistics (CCEB) at the University of Pennsylvania Medical Center to serve as the Data Coordinating Center (DCC) for the Interstitial Cystitis Clinical Trials Group (ICCTG). The proposed DCC will provide administrative, biostatistical, urological, pathological, clinical data management and researc computing leadership for the ICCTG in the conduct of a series of randomized, controlled clinical trials (RCTs) at five Clinical Research Centers (CRCs) to investigate current and novel medical therapies for Interstitial Cystitis (IC) During Phase 1, the DCC will guide the design of ICCTG master protocols, including decisions related to baseline screening and data collection on symptoms, quality of life, and laboratory specimens, and during Phase 11, the DCC will guide the conduct of multiple RCTs. The DCC will provide expertise in the design and conduct of clinical trials, pain measurement, selection of outcome measures, and identification of prognostically different subgroups of patients. Based on completed analyses of data from the Interstitial Cystitis Data Base (ICDB) Study, as well as extensive new analyses underway at the CCEB a) identification of clusters of biopsy feature subgroups, b) correlating symptoms, clinical findings & family/medical history with biopsy specimen features), this DCC is uniquely positioned to provide valuable experience-base biostatistical leadership for the ICCTG during the planning phase of these clinical trials. The DCC will provide the clinical trials and biostatistics expertise for conducting specific clinical trial protocols, as illustrated by the two Protocols included in this proposal. To support these multi-center, multiple protocol RCTs, the DCC will provide the data management and research computing expertise necessary to design and implement data quality assurance, reporting and data collection via a secure World Wide Web (WWW)-based data management system, deployed on existing hardware at the CRCs, to facilitate data entry, verification and validation at the CRCs, and data transmission ove the Internet to the server at the DCC. This system will support subject enrollment, randomization and data collection at the CRCs, and tracking of subjects, data, and specimens at the DCC. The DCC will execute procedures for data security and access, data quality control, storage and back-up, and will provide periodic reports of accrual, follow-up, and data. The DCC will also provide the logistical and administrative support for the conduct of all multi center RCTs. The DCC will organize meetings of the Steering Committee, coordinate the development and distribution of the Protocol and Manual of Operations for each of the clinical trials, and provide the NIDDK Program Office, Steering Committee, External Advisory Committee, and Data and Safety Monitoring Board with interim data summaries, final statistical analyses and collaboration on all scientific publications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIAGNOSTIC CHALLENGES IN IC (AND MALE CPPS) Principal Investigator & Institution: Dimitrakov, Jordan D.; Queen's University at Kingston Kingston K7l 3N6, Canada Kingston,

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Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The etiology and pathogenesis of interstitial cystitis (IC) and its related condition in men, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has remained elusive. This has hampered development of mechanistic treatment strategies for these common, chronic and distressing medical conditions. We believe that IC and perhaps CP/CPPS are a spectrum of complex but inter-related genetic and acquired diseases resulting from the interaction of several genes regulating immune/inflammatory and neurogenic parameters and environmental factors/circumstances or exposure, culminating in the combination of pain, frequency, urgency and sexual specific symptoms. New research has delineated the dynamic and powerful association of the immune and neurogenic system in pain activation. An immune-modulated neurogenic model of IC illuminating the action of immune derived substances and pain related substances might be important in discovering the determinants of pain, voiding dysfunction and gender specific sexual problems. This inter-related dynamic model of IC disease pathogenesis could be explored for potential avenues leading to novel diagnostic and treatment strategies. We plan to identify and evaluate the sensitivity and specificity of several novel nerve and inflammation related markers in the diagnosis and follow up of IC (and CP/CPPS). By correlating the levels of urine immune and pain related substances to disease mechanisms, severity and progression, we may be able to create a human disease specific model for diagnosis and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DR ADHESINS IN E COLI RENAL VS BLADDER TROPISM Principal Investigator & Institution: Das, Margaret; Obstetrics and Gynecology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-AUG-2001 Summary: Escherichia coli expressing Dr adhesin cause pyelonephritis and related AFA-III cause cystitis. This study seeks to identify the receptor-binding site of DraE and provide insights into the mechanism of renal vs bladder tropism. Aim 1. To identify and characterize domains of Dr fimbriae that interact with DAF. We propose that N-terminal surface exposed residues of DraE form an assembled epitope that bind DAF. The hydrophilic domain Val30 to Pro42 will be mutated by alanine-scanning mutagenesis and mutants analyzed for binding and invasion of DAF+ CHO cells. Aim 2. To investigate the pathogenic mechanism that determines kidney vs bladder tropism of Dr+ E. coli. DraE and AWE differ in three amino acids (D54N, T90M, I113T). Dr+E. coli infect the kidneys while AFA-III+ E. coli infect the bladder. Amino acids of DraE will be replaced with those of Afa3E and renal tropism analysed using isogenic mutants of E. coli HI 11128 in mice. Aim 3. To study attachment and cell invasion by DraE and Afa3E adhesins. DraE is more invasive than Afa3E. We will study invasion using polystyrene beads coated with purified DraE mutants, immunogold staining and electron microscopy. Resolving the binding domain will enable design of peptide inhibitors against the common receptor preventing bacterial dispersion and cell invasion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF EARLY-IN-LIFE BLADDER STIMULATION ON ADULTS Principal Investigator & Institution: Randich, Alan; Professor; Psychology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294

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Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Pain originating from the urinary bladder is a common clinical entity affecting more than 50% of females at some time in their lives. Some conditions are easy to treat, but others, such as interstitial cystitis (IC) have proven resistant to diagnosis and treatment. There are multiple proposed etiologies for IC with the common theme of an eventual sensitization/activation of sensory elements: abnormalities in the periphery lead to central neurophysiological changes that become expressed as enhanced sensory (pain-urgency) and reflex responses (i.e. reduced bladder capacity) which may outlast "triggering" events within the bladder. In somatic systems, it has been demonstrated that exposure to painful stimuli during early life can produce permanent changes in the neuroanatomical and neurophysiological substrates that process nociceptive information. Since 10-28% of adult patients with IC report urinary bladder symptoms as children a logical avenue for exploration is an examination of the effects of early-in-life painful bladder experiences on bladder responses in adults since individuals who are "primed" for hypersensitivity of the bladder could have pain that is both easily triggered and manifested as a sustained response to normally self-limited events. The hypothesis central to these studies is: A peripheral and spinal neuronal sensitization process initiated by early-in-life, highintensity primary afferent activation, can enhance susceptibility to pathological urinary bladder pain as an adult. This early-in-life process leads to a hypersensitive state that is manifested by lowered intravesical stimulus thresholds needed for pain evocation and augmented responses to supra-threshold stimuli. To test this hypothesis reflex, primary afferent neuronal and spinal neuronal responses to urinary bladder distension (UBD) will be characterized in rats, which are given high-intensity UBD and/or inflammatory stimuli (intravesical zymosan) in the neonatal, pre-pubescent or post-pubescent periods. These exploratory studies will lay the groundwork for potential, novel therapeutic modalities for the treatment of urinary bladder pain by identifying substrates of hypersensitivity development and thereby treatment of urinary bladder pain by identifying substrates of hypersensitivity development and thereby presenting targets for intervention. Translation to the treatment of IC would be highly probable. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOCYTIC TRAFFIC IN BLADDER UROEPITHELIUM Principal Investigator & Institution: Apodaca, Gerard L.; Associate Professor of Medicine; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: The specialized umbrella cells lining the mucosal surface of the urinary bladder form a barrier between the urine and the underlying muscle layers and vasculature. When this barrier function is disrupted, disease may ensue (e.g. in interstitial cystitis or bacterial infection). The barrier function of the uroepithelium depends on several factors including: formation of a polarized epithelium with tight junctions, presence of an apical plasma membrane highly impermeable to water and urea, and a surface layer of glycosaminoglycans. Understanding how barrier function is disrupted in disease requires that normal barrier function and development of the uroepithelium be defined. As such, the first aim of this proposal is to characterize the development of polarity and uroepithelial phenotype in a newly-established primary uroepithelial cell culture model. These cultures obtain high transepithelial resistance (up to 10,000 omegacm2), and have apical sodium channel activity. Like umbrella cells found in vivo, cultured umbrella cells have an asymmetric unit membrane and express

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the AE-31 antigen and uroplakins. In addition, two aspects of umbrella cell barrier function that are only poorly understood will be examined. These include the requirement that the umbrella cell accommodate large changes in bladder volume likely to be mediated by fusiform vesicles that are inserted/removed from the apical membrane in response to filling and emptying of the bladder - as well as the ability of these cells to limit the amount of apical endocytosis and prevent endocytosed urine from reaching the underlying tissue. The hypothesis that fusiform vesicle exocytosis is regulated by stretch and will be modulated by stretch-sensitive channels, secondary messenger cascades, and SNARE fusion complexes will be examined in Aim II. The effects of stretch receptor antagonists on fusiform vesicle exocytosis will be examined, as will modulators of [Ca2+]i, cAMP production, protein kinase C activation, and SNARE fusion proteins. In Aim III the following hypotheses will be tested: (1) apical endocytosis will be inhibited during periods of bladder filling; (2) endocytosis will be stimulated following voiding; and (3) internalized urine will be primarily recycled to the apical pole of the cell or be delivered to lysosomes. A combination of biochemical and morphological tools will be used to characterize the endocytic and postendocytic traffic of stretched and unstretched primary cultured and freshly isolated uroepithelium. The proposed experiments will provide novel insights into normal uroepithelium development and barrier function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF CHRONIC PELVIC PAIN Principal Investigator & Institution: Clemens, J Quentin.; Assistant Professor; Urology; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2006 Summary: (Provided by Applicant): The primary aim of this application is to obtain novel information about chronic pelvic pain of bladder origin (CPPBO) in order to determine the magnitude of the problem and its cost to society. This study builds on our ongoing collaborative work with the NIH Chronic Prostatitis Collaborative Clinical Research Study, in which demographics, risk factors, quality of life, and health resource utilization are being evaluated in men with chronic voiding symptoms and pelvic pain. These studies are ongoing, and we will utilize similar methods in men and women in order to obtain consistent data for comparison between the sexes. The specific aims are: 1) to assess the prevalence and incidence of CPPBO. A clinically useful definition of the syndrome will be described, and this definition will be used to assess the prevalence of the syndrome in a large, diverse patient population. Using the same definition, the incidence of new cases will subsequently be determined over a three-year time period; 2) to determine risk factors for the development of CPPBO. A case-control study will be performed using age- and gender-matched controls in order to evaluate for medical conditions and lifestyle factors which are associated with the syndrome; and 3) to evaluate the effect of CPPBO on patient quality of life and health resource utilization. To conduct this study, two populations will be utilized. A database of patients from the Kaiser Permanente Foundation Hospitals in Oregon will be used to assess population prevalence and incidence rates and direct medical costs. Questionnaires will be mailed to a random sample of the Kaiser Permanente patients to obtain detailed information about symptoms and quality of life (QOL). In addition, patients diagnosed with CPPBO at the Northwestern Memorial Faculty Foundation Urology Clinic will undergo a more extensive questionnaire evaluation to analyze medical and lifestyle risk factors for the presence of CPPBO and to obtain additional QOL and health resource utilization information. Answers from the Urology clinic patients will be compared with those of

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age-and gender-matched controls in a case-control study design. This project will provide novel, population-based epidemiologic information about chronic pelvic pain of bladder origin in both men and women, and will help to further define the public health burden of this extremely common condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPITHELIALLY-DERIVED FACTORS IN INTERSTITIAL CYSTITIS Principal Investigator & Institution: Hanrahan, John W.; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): ATP is released to the basolateral side of the urinary bladder epithelium during stretch and binds to purinoceptors on sub-epithelial sensory afferent neurons. According to one theory for the pathogenesis of interstitial cystitis (IC), epithelial ATP release becomes elevated and this contributes to inflammation and pain. Little information is available regarding the mechanism of mechanically-induced ATP release from transitional epithelia or its modulation. We will explore the ATP hypothesis by developing new approaches to study ATP release from acutely-isolated rat urinary bladder epithelial cells and cells maintained in primary culture. Bladder epithelial cells will also be cultured in hollow fiber bioreactors so that other epitheliallyderived factors that may be co-released with ATP can be collected and identified. To firmly establish exocytosis as the primary release mechanism in uroepithelium, the involvement of SNAREs, intracellular free [Ca], vesicular pH, phosphatidyl 4,5bisphosphate, and protein kinases will be explored. Molecular aspects of mechanicallyinduced ATP release and its regulation will be studied using three approaches: 1) release will be monitored macroscopically when cells are distended in a luminometer, 2) ATP release will be monitored microscopically by counting single photons to image extracellular luciferase bioluminescence, and 3) total internal reflection fluorescence imaging of single exocytotic fusions will be used. Force will be applied to single cells to induce ATP release or vesicle fusion. To identify molecular components involved in bladder epithelial force transduction and exocytosis, cultured cells will be transfected with dominant negative constructs and small interfering RNAs to inactivate key proteins in the cytoskeleton, cell adhesion complexes and vesicle trafficking machinery. Finally, maneuvers that influence ATP release in vitro will be studied in rats by recording from afferent sensory neurons that innervate the rat urinary bladder. These studies will provide new insights into the mechanism and regulation of uroepithelial ATP release, and may identify other factors that are co-released in interstitial cystitis. Understanding the molecular basis of mechano-sensitive ATP release may suggest molecular targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFECTION

FUNCTIONAL

GENOMIC STUDIES

OF

URINARY TRACT

Principal Investigator & Institution: Gordon, Jeffrey I.; Professor and Head; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: We have used functional genomics (i.e., DNA microarrays with follow-up real time quantitative RT-PCR and in situ hybridization analyses) to examine the bladder responses of adult C57B1/6 female mice during the first steps of infection with virulent (FimH+) and isogenic avimlent (FimH-) UPEC strains. Project 3 will extend

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these analyses with four specific aims. (1) Further characterize the evolution of the response of the adult female C57B1/6 mouse bladder to infection with two genotyped clinical isolates. Our previous studies focused on the acute phase of infection with the cystitis isolate NU14. We will now use DNA microarrays to profile gene expression in the bladders of adult female C57B1/6 mice from 1.5h to 6 weeks after infection with UTI89 (a virulent strain whose geneme will be sequenced in Project 1), and a genotyped asymptomatic bacteriuria (ASB) strain. The temporal evolution as well as the celtular origins of selected responses will be defined using real time quantitative (q) RT-PCR, laser capture microdissection (LCM), in situ hybridization, and multi-label immunohistochemical analyses. (2) Define the impact of specified UPEC genes on the response of the adult female C57B1/6 mouse bladder to infection. We will examine host responses to isogenic strains of UPEC that have engineered mutations in genes expected to alter various steps in the proposed 6 step pathogenic cascade. These mutants will be generated in Project 1 and will include (el) genes targeted based on results obtained from the UT 189 genome sequence, results obtained from differential genotyping of clinical strains, and results garnered from studies of bacterial gene regulation; (b) genes identified during screens of a random transposon-tagged library and (c) mutants in already suspected virulence factors. (3) Define the response of the adult female C57B!/6 mouse bladder to a Gram-positive uropathogen. Enterococcus spp are an important cause of nosocomial infection. A functional genomics-based comparison of the responses to infection with isogenic wild type and fimH strains of an Enterococcus faecalis cystitis isolate will provide insights about how the bladder responds to attachment of Gram-positive uropathegens (4) Define host genes that regulate responses to infection with isogenic wild type and mutant strains of UPEC and E. faecalis. Toll-like receptor (TLR) pathways are involved in the response to infections by both Gramnegative and Gram-positive bacteria. We will perform a comparative functional genomics analysis of the host response to FimH+ UPEC and FimH + E. faecalis in adult female C57BI/6 mice homozygous for wild type tlr alleles, versus the responses of C57B1/6 mice homozygous for tlr4 or tlr2 nuU alleles. We will also examine the contributions of inducible nitric oxide synthase (iNOS), matrilysin (MMP-7) and A20 by infecting genetically engineered C57B1/6 mice homozygous for null alleles of these genes with wild type and mutant strains of bacteria characterized in aims 2 and 3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC DETERMINANTS OF URINARY TRACT INFECTION IN WOMEN Principal Investigator & Institution: Hooton, Thomas M.; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Acute uncomplicated urinary tract infections (UTIs) occur in an estimated 711 million women each year and annual costs of caring for these women are thought to approach $1.6 billion. While most young women experience only sporadic episodes of cystitis, approximately 20-30% suffer from recurrent infections, 5% from highly recurrent infections, and as many as 5-10% develop acute pyelonephritis, often necessitating hospitalization and parenteral antimicrobials. In the aggregate, UTIs in young women result in substantial morbidity, time lost from work, and medical costs. An improved understanding of the pathogenic mechanisms underlying recurrent UTIs and pyelonephritis could result in novel approaches to their prevention and reduced morbidity and antimicrobial use. Behavioral factors such as sexual and contraceptive practices have been shown to be strongly associated with risk of recurrent UTI (RUTI) in

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these women, and there is increasing evidence that recurrent RUTIs are also associated with genetic factors. Genetic variation has been used to implicate genes in the susceptibility to many infections. The main objective of this project is to determine whether DNA variations in selected candidate host genes influence human susceptibility to RUTI or pyelonephritis. Based on accumulating evidence implicating them as important in animal models of UTI, the candidate genes selected for study are toll-like receptors (TLR2, TLR4, and TLR5), chemokine receptors (CXCR1 and CXCR2) and interferon gamma receptors (IFN-gammaR1 and IFNgammaR2). In this project, we will perform full gene sequencing of these candidate genes in 100 women with a strong family history of RUTI or pyelonephritis to discover novel nucleotide variations in these groups. We will then examine, via a case-control study of 1700 women that identifies all incident cases and two population-based control groups, whether known or novel genetic variations in these candidate genes are associated with the syndromes of RUTI and/or pyelonephritis. We will also determine how genetic variations may modify the association between behavioral risk factors and RUTI and pyelonephritis. A better understanding of the role of genetics in the pathogenesis of RUTI and pyelonephritis, and the relationship between behavioral factors and genetic variations, is critical to the development of optimal prevention and management strategies for these very common syndromes in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLYCOSAMINOGLYCANS FOR IC PATHOPHYSIOLOGY AND PROGNOSIS Principal Investigator & Institution: Lokeshwar, Vinata B.; Urology; University of Miami Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Despite superb efforts of patient advocacy groups, our insight into the etiology, diagnosis and treatment for interstitial cystitis (IC) is still inadequate. Since the luminal glycosaminoglycan (GAG) layer protects the bladder urothelium from noxious substances in urine, alterations in urothelial GAGs may be associated with IC pathophysiology. Urinary levels of total (i.e., non-sulfated and sulfated) GAGs and hyaluronic acid (HA) are elevated in IC patients with severe disease, as judged by the validated O'Leary-Sant questionnaire and clinical index. These patients' urine also contain one or more unique GAG species and a high molecular mass HA species. Urinary total GAG levels and GAG profile appear to be accurate markers for monitoring disease severity, regardless of the type of treatment the patients are undergoing. IC urothelial cultures secrete higher levels of matrix metalloproteinases (MMPs)-2 and -9, when compared with normal urothelial cells, suggesting an association between MMPs and this disease. This proposal is designed to investigate the involvement of IC specific GAGs, high molecular mass HA and MMPs in the pathophysiology of IC and how GAG-like substances may bring about symptom relief. Furthermore, to evaluate in a multi-center trial the usefulness of total urinary GAG and HA levels, GAG and HA profiles and urinary MMP levels in the follow-up of IC patients. To identify IC-specific GAGs and their cellular source, these GAGs will be purified from IC patients' urine and primary urothelial culture conditioned media (CM), by sequential liquid chromatographies, digestion with GAG-degrading enzymes and HPLC (Aim 1). The cellular basis of qualitative and quantitative alterations in GAGs, will be evaluated by performing a pair-wise comparison of GAG levels and GAG profile in urine, tissue extracts and urothelial CM from IC patients with varying degrees of disease severity. The involvement of IC-specific GAGs in IC pathophysiology and of

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GAG-like substances in causing symptom relief, will be evaluated by cDNA microarray analysis of changes in gene expression in normal and IC urothelial cells treated with ICspecific GAGs and pentosan polysulfate, respectively (Aim 2). To understand their association with IC, HA levels; HA profile and MMP levels will be analyzed in urine, tissue extracts and urothelial CM from IC patients with varying degrees of disease severity. Changes in normal urothelial gene expression following treatment with high molecular mass HA will be evaluated by cDNA microarray analysis, and compared with gene expression in IC urothelial cells, to reveal the involvement of HA in IC pathophysiology (Aim 3). In a multi-center trial, the usefulness of total GAG levels, GAG and HA profile and MMP levels in IC patient follow-up and their use for monitoring treatment response will be evaluated (Aim 4). The proposed study will reveal the function and diagnostic potential of urothelial GAGs (including HA) and MMPs in 1C pathophysiology. Furthermore, it might yield a test or a combination of tests that can be used in the follow-up of IC patients and for monitoring 9 treatment responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: H2O2-PRODUCING LACTOBACILLI AND POSTMENOPAUSAL UTI Principal Investigator & Institution: Gupta, Kalpana; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) Urinary tract infections affect over 7 million women per year, and the incidence of UTI increases with advancing age. Although marked strides have been made in our understanding of the pathogenesis of UTI in young adult women, the pathogenesis and epidemiology of UTI among postmenopausal women remain poorly understood, especially among the noninstitutionalized segment of the population. Vaginal colonization with E. coli has been shown to be an important event preceding UTI, and it is highly prevalent in postmenopausal women. In vitro studies suggest that the predominant constituents of normal vaginal flora, H202-producing lactobacilli, are inhibitory to E. coli. Our recent data demonstrate that there is, indeed, an inverse relationship between the presence of H202-producing lactobacilli and E. coli vaginal colonization in premenopausal women with recurrent UTI. However, the prevalence of H202-producing lactobacilli, and their relationship to vaginal E. coli colonization and to the incidence of UTI among postmenopausal women has not been characterized. A prospective evaluation of the incidence of and risk factors for UTI in 1000 community-dwelling postmenopausal women (DK43134, Stephan D. Fin, MD, MPH) has been initiated at the Group Health Cooperative of Puget Sound, a population-based HMO in western Washington. Based on our findings in premenopausal women, we are proposing additional studies which will enable us to (1) establish the prevalence of vaginal lactobacilli, characterized by H202 status and by species, in postmenopausal women; (2) examine the relationship between H202-producing lactobacilli and E. coli vaginal colonization; (3) relate this information to the incidence of UTI and asymptomatic bacteriuria in postmenopausal women while accounting for exposures such as estrogen use, diabetes, and antimicrobial use; (4) assess the prevalence of urovirulence genes in E. coli strains causing cystitis in postmenopausal women; and (5) assess the feasibility of using a lactobacillus probiotic to prevent UTI in postmenopausal women. These additional studies will entail a combination of epidemiological, biostatistical, and laboratory methods which, in combination with structured didactic and classroom instruction, will provide an

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excellent training experience for the development of the Candidate into a successful, independent, clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE MEDIATED BLADDER INFLAMMATION Principal Investigator & Institution: Ratliff, Timothy L.; Andersen-Hebbeln Professor; Urology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 31-JAN-2003 Summary: (Adapted from the Applicant's Abstract): The bladder, as a mucosal immune organ often exposed to foreign antigens, is linked to the expression of immunity. Examples of bladder-associated immune responsiveness include bacterial infection, response to therapeutic antigens such as BCG (used in treatment of interstitial cystitis and bladder cancer), and although controversial, some have suggested a role for immunity in interstitial cystitis. Considerable data has been published on the histopathology of bladder inflammation. Reports have shown the predominant infiltrating T cell to be CD4+ helper T cells and also have demonstrated the presence of HLA DR expression on transitional epithelial cells. While the expression of immunity in the bladder has important disease-related consequences, the mechanisms by which intravesical antigens initiate immunity and the role of MHC Class II expressing epithelial cells in the expression of immunity have not been established. The objective of the studies outlined herein is to characterize the initiation, expression and regulation of antigen specific CD4+ T cell immunity in the bladder. The working hypothesis is that the activation and expression of CD4+ T cell immunity in the bladder is regulated by bladder-associated cytokines and the antigen presenting function of bladder epithelial cells. The hypothesis will be tested through the in vitro characterization of the immunomodulatory potential of bladder epithelial cells and in vivo using the ovalbumin (OVA)-specific CD4+ DO11.10 T cell receptor transgenic mouse model. The studies outlined with DO11.10 T cells, which can be identified with a unique clonotypic antibody, will provide a basis for the critical evaluation of the hypothesis in an in vivo model. Preliminary data show that bladder epithelial cells function as antigen presenting cells for CD4+ T cells, appear to provide sub-optional activation of CD4+ helper T cell responses, and function as target cells for CD4+ T cell-mediated killing through Fas-induced apoptosis. These observations form the basis for experiments aimed at characterizing T cell-induced bladder inflammation, defining regulatory mechanisms of the inflammatory response, and developing approaches for modifying the inflammatory response through re-directing and/or abrogating CD4+ T cell responses. To accomplish these objectives, the following specific aims will be pursued: (1) characterize the effects of antigen presentation by bladder epithelial cells on CD4+ T cell responses in vitro, (2) characterize the effects of bladder epithelial cell antigen presentation on CD4+ T cell activation in vivo using the ovalbumen-specific CD4+ DO11.10 T cell receptor transgenic model, and (3) determine the effects of CD4+ T celldirected chronic bladder inflammation on bladder function and evaluate strategies for modifying the response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE MEDIATORS IN INTERSTITIAL CYSTITIS Principal Investigator & Institution: Peters, Kenneth M.; Director of Clinical Research; William Beaumont Hospital 3601 W Thirteen Mile Rd Royal Oak, Mi 480736769 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2002

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Summary: Interstitial cystitis (IC) is a severe debilitating bladder disease of unknown etiology and no cure. A recent double-blind trial using intravesical Bacillus Calmette Guerin (BCG) to treat IC demonstrated a 60% clinical response rate to a single six week course of BCG. When subjects who responded to BCG were followed for a minimum of two years, 89% continued to have an excellent response, despite no additional treatment of their IC. The durability of this treatment leads one to speculate on the mechanism in which intravesical BCG may treat interstitial cystitis. There is evidence that interstitial cystitis may be mediated by a T-Helper Cell type-2 (Th-2) response within the bladder. Cytokine analysis from the urine of IC subjects showed elevated levels of Interleukin-6 and inhibitors of interleukin-2, suggesting a Th-2 response. In addition, similar autoantibodies have been identified in both atopic dermatitis, a Th-2 mediated disease, and interstitial cystitis. However, the role of the immune system in the etiology of IC remains controversial. We hypothesize that interstitial cystitis is a Th-2 mediated disease leading to chronic inflammation and that intravesical BCG is effective by converting the cytokine milieu to a Th-1 profile, leading to reparative conditions and long-term clinical response. Specifically, this study will: 1) determine the urine cytokine profiles in subjects meeting the NIDDK criteria for interstitial cystitis and in health control subjects; 2) determine in a blinded fashion the changes in urinary cytokines during six weekly instillations of either bacillus Calmette-Guerin (BCG) or placebo and at regular intervals during a 6 month follow-up; 3) correlate changes in cytokines with clinical response; and 4) determine whether a certain cytokine profile cytokine profile can predict clinical response to intravesical BCG therapy. This study will involve subjects enrolled in our present clinical trial of intravesical BCG therapy for IC. Cytokine levels will be determined in triplicate by enzyme-linked immunosorbant assays and normalized against urine creatine. Study results will be analyzed by non-parametric methods. In addition, a receiving operating characteristic analysis will be completed to determine the critical cytokines levels for predicting clinical response to treatment. In summary, this study will determine the cytokine profile in IC subjects and healthy subjects. By correlating the changes in cytokine levels before, during and following intravesical BCG therapy, we will establish the role of these cytokines in IC and use the pattern of change as a means to predict subject response to therapy. Additionally, this study will open a new avenue of research with specific long-term potential for the development of more effective, less toxic treatments of IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFLAMMATORY SIGNALING MECHANISMS OF THE CGRP RECEPTOR Principal Investigator & Institution: Porter, James E.; Pharm/Toxicology/Therapeutics; University of North Dakota 264 Centennial Drive Grand Forks, Nd 58202 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The long-term goal of this research is to advance the understanding of cellular mechanisms that contribute to the inflammatory etiology of interstitial cystitis (IC). The immediate goal of this project is to characterize signaling pathways initiated by calcitonin gene-related peptide (CGRP) receptor activation that lead to increased production of pro-inflammatory compounds. CGRP and other neuropeptides released from sensory fibers contribute to neurogenic inflammatory pain by potently mediating vascular changes that are a hallmark of inflammation. The subsequent increase in vascular permeability leads to extravasation, emigration and activation of leukocytes at the site of injury. Activated leukocytes go on to release additional chemical mediators (e.g., prostanoids), further promoting the edema and

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hypersensitivity of inflammatory pain. Increasing evidence suggests that neurogenic inflammatory pain is a major component of IC pathophysiology. This study is guided by the hypothesis that CGRP is an important mediator of specific neurogenic inflammatory pain processes. Therefore, a detailed understanding of the CGRP inflammatory signaling pathway may yield insights toward new therapeutic targets for the management of IC. CGRP receptor binding sites expressed on a human monocytic cell line (THP-1) have initially been characterized. Moreover, CGRP mediated increases in cAMP, MAP kinase phosphorylation and cyclooxygenase-2(COX-2) production has been demonstrated for these THP-1 cells. However, specific relationships between these signaling pathways and CGRP receptor activation remain unclear. Aim one will investigate the hypothesis that a CGRP mediated rise in cAMP production is directly linked to an increase in COX-2 generation. Aim two will test the hypothesis that CGRP mediated induction of COX-2 leads to an increased biosynthesis of arachidonic acid metabolites known to induce swelling and hyperalgesia. Results from completion of these specific aims will further our understanding of signaling mechanisms mediated by CGRP receptor activation that participate in the pathophysiology of inflammatory pain, implicated in the etiology of IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INNOVATIVE INTRAVESICAL TREATMENT APPROACH FOR IC Principal Investigator & Institution: Bhavanandan, Veer P.; Professor; Biochem and Molecular Biology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Interstitial cystitis is poorly understood, and the causes and pathophysiology for IC are still unknown. Many theories have been proposed about the etiology of IC, but none has been definitively proven. There are no cures for IC and clinicians use a variety of empiric treatments, based on the proposed causes for IC. However, none of these treatments are consistently effective, and some patients remain unable to find any relief. One popular theory about IC is that the glycocalyx of the bladder epithelium is deficient. Accordingly, some of the current treatments are aimed at replacing the missing glycoconjugates by intravesical or oral administration of sulfated polysaccharides, such as heparin and pentosan polysulfate (Elmiron). It is unknown why these treatments show improvement of symptoms in only some IC patients, and why the response is usually slow. One possible reason is that the highly anionic and readily water-soluble sulfated polysaccharides do not adhere to the bladder well enough to exert their beneficial effect. An exploratory study is proposed for the development of an innovative approach that should not only increase the efficiency of sulfated polysaccharides for patients who respond, but may also benefit some patients who do not currently respond. The plan is to improve the binding and thereby strengthen and prolong the adherence of intravesically administered drugs to the bladder. The experimental strategy is to modify the sulfated polysaccharides with specific saccharide ligands, so that they will bind to endogenous lectins in the bladder. In order to choose the saccharide structures for this purpose it is first necessary to identify the lectins present in the bladder epithelium of rabbit (an animal model for initial binding studies) and human. Preliminary studies have demonstrated the presence of galactose- and Nacetylglucosamine-binding lectins in both rabbit and human bladders. Further detailed investigations are needed to complete the biochemical characterization of the major bladder lectins and specifically, elucidate their saccharide specificities. Once identified, the saccharide ligands will be conjugated to sulfated polysaccharides and the binding of

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the conjugates to bladder will be evaluated. Although the initial studies will be on sulfated polysaccharide treatments of IC, the same strategy could also be applied to improve treatment of various other bladder diseases. For example, prolonged binding of antibiotics to the urothelium may help to treat or prevent urinary tract infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERSTILAL CYSTITIS CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Chai, Toby C.; Associate Professor; Surgery; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): Interstitial cystitis (IC) is a condition that remains enigmatic both in diagnosis and treatment. Characteristic symptoms include chronic pelvic pain, urinary urgency, and urinary frequency. While these symptoms seem specific, in fact, they can vary widely, especially the description of the pain (nature, location, chronicity, flares). For most clinicians, chronic pelvic pain is the symptomcomplex most difficult to treat effectively. Because the etiology(s) for IC is (are) unknown, treatment has been entirely empiric. For the last 5 years, we at the University of Maryland have participated in the Interstitial Cystitis Clinical Trials Group (ICCTG) in hopes of scientifically validating certain treatments used for IC as well as studying potential new agents. Two randomized trials were completed during this time. The lessons learned from the ICCTG translate into specific aims for the proposed upcoming ICCRN trials. 1. There needs to be a new "definition" for IC rather than the current NIDDK-criteria established in 1987. The old criteria are too restrictive and no peerreviewed objective diagnostic criteria are included. 2. Treatment outcomes of IC must be correlated with changes in objective parameters other than symptom scores and voiding diaries. 3. Enrollment of newly diagnosed IC patients must be maximized in the upcoming trials. Studying newly diagnosed IC patients may shed some light as to the natural history as well as response to treatment in this specific population. To this end, we are collaborating with private practice urologists who primarily see early IC patients and should help provide adequate enrollment of these types of patients into clinical trials. The trial that we propose to conduct is botulinum toxin-A (BTX-A) bladder injections. Recent data suggest that BTX-A has an anti-sensory action in the bladder. The group of investigators participating in this grant represent leaders in IC research. They have experience in recruiting IC patients into clinical trials, performing translational and basic science IC research. The continued advancement in diagnosis and treatment of IC depend on this type of collaboration in a multi-disciplinary environment such as that which exists at University of Maryland. The goals of the University of Maryland clinical site are to maximize enrollment of IC patients into innovative clinical trials, maintain highest retention rates possible and acquire high quality data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERSTITIAL CYCTITIS CLINICAL RESEARCH NETWORK (ICCRN) Principal Investigator & Institution: Mayer, Robert D.; Urology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The primary objectives of this proposal are to continue our participation in the Interstitial Cystitis Clinical Research Network (ICCRN), (formerly Interstitial Cystitis Clinical Trials Group) in order to develop and

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conduct randomized controlled multicenter studies of therapies for interstitial cystitis. The objectives will be achieved by: a. Establishment of a collaborative group of clinical trials centers with clinical expertise in chronic pelvic pain, clinical pain management and interstitial cystitis. b. Development and design of randomized therapy protocols for interstitial cystitis. c. Development and completion of ancillary studies that will provide further understanding of interstitial cystitis. d. Determination if there is a different response to therapy between newly diagnosed and chronic, long term patients with the disorder. e. Recruitment of sufficient numbers of patients into these clinical trials. f. Collaboration with other ICCRN sites and Data Coordinating Center to analyze and interpret results. g. Participation in the Urological Chronic Pelvic Pain Syndrome Collaborative Group to facilitate clinical trials and to develop a clinically relevant definition of the urologic chronic pelvic pain syndromes. There will be an initial 12month period of collaborative protocol/manual operations development followed by 48 months of patient recruitment with concurrent data analysis and reporting. The data obtained from these randomized controlled studies will define the effectiveness of various therapies for interstitial cystitis, further our understanding of the factors initiating the diseases' development, progression, remissions and responses(s) to treatment and improve the quality of life of patients suffering from interstitial cystitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Burks, David A.; Senior Staff Urologists; Urology; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): Interstitial cystitis is a chronic debilitating disease characterized by urinary frequency, urgency and bladder pain. Despite the first descriptions of this disease by Guy Hunner in 1914, it still remains "The Great Enigma." The disease continues to defy a consensus definition, a definable pathophysiology or a reliably effective treatment. Multiple theories of pathogenesis have spawned a myriad of mostly ineffective treatments. Many physicians either doubt, or are unaware of the existence of this disease causing significant delay in diagnosis for many patients, especially men and children, where the disease is most poorly characterized. Since 1987 the NIH has begun a systematic, evidence-based effort to define interstitial cystitis determine its biochemical and clinical characteristics and evaluate novel therapies. Beginning with the NIDDK Workshop and Consensus Conference, the definition of interstitial cystitis has evolved from a restrictive instrument used for research papers, to a more inclusive criteria developed by the Interstitial Cystitis Data Base Group. The Interstitial Cystitis Clinical Trials Group proved that a collaborative multi-center group could recruit patients into rigorous, novel treatment protocols. The major objective of this grant is to develop the Interstitial Cystitis Clinical Research Network to continue the evolution in characterizing this disease. We propose evaluating a novel therapy, IPD-1151T, an immune system modulator with possible efficacy in interstitial cystitis patients. A published pilot study showed significant improvement in symptom scores with minimal side effects. The ICCRN will work in collaboration with the Chronic Prostatitis Clinical Research Network to investigate interstitial cystitis as a subset of chronic pelvic pain disorders of the bladder. A coordinated effort to develop common patient evaluation and treatment protocols, will allow an overarching analysis of these urologic pain syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Payne, Christopher K.; Associate Professor; Urology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): This application proposes that Stanford University Center for Female Urology and NeuroUrology participate as one of several National Clinical Centers in a cooperative effort to develop clinical trials for the study of interstitial cystitis (IC). The Principal Investigator intends to participate fully as a member of the steering committee in designing and carrying out multicenter randomized controlled clinical trials (RCTs). The investigative group at Stanford will work in parallel with the centers conducting trials for investigation of chronic prostatitis. A simultaneous application for that effort is being submitted. This is a critical juncture for IC research. While appreciation of the prevalence and impact of the disease is growing, little headway has been made in identifying the underlying etiology or finding reliably effective treatment. More importantly, the very definition of IC and pelvic pain syndromes is under active debate--are all patients with pelvic pain simply varying manifestations of a single underlying disorder or are there important clinical distinctions between IC, vulvadynia, chronic prostatitis, and pelvic floor dysfunction? The relevance of standard diagnostic tools has been challenged. Bladder distention under anesthesia may be neither sensitive nor specific. Neither urodynamic testing nor bladder biopsy provides specific diagnostic information. A simple office trial of intravesical potassium instillation purported to identify IC totally failed to predict response to therapy in a RCT. These and other critical issues will only be settled by carefully designed, large scale RCTs. The ICCRN should focus on the following specific aims: 1) determining the clinical utility of currently diagnostic tests for IC and evaluating new tests 2) developing evidence based algorithms for the work-up of IC patients involved in clinical research 3) developing relevant clinical protocols that involve the entire spectrum of IC patients 4) to test novel therapies for IC as they become available. Stanford is ideally suited for this project due to a long history of interest in IC, a Principal Investigator with recognized expertise in clinical research, an ethnically diverse patient base, and demonstrable success recruiting patients for IC research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK (ICCRN) Principal Investigator & Institution: Nickel, J Curtis.; Queen's University at Kingston Kingston K7l 3N6, Canada Kingston, Timing: Fiscal Year 2003; Project Start 02-SEP-2003; Project End 28-FEB-2008 Summary: The RFA specifically requests that the applicants confirm their interest and ability to take part in clinical treatment trials in Intersitial Cystitis (IC). The Queen's University Intersitial Cystitis Research Group is established under the directorship of Dr. J. Curtis Nickel in Kingston, Canada and recently expanded to take part in the NIH ICCTG RCT #2. The Queen's University Intersitial Cystitis Research Group has enrolled 255 patients in 12 clinical trials, specifically in clinical IC treatment studies (this does not include the many patients recruited for etiology and diagnostic studies during the same time period). As part of the NIH ICCTG, the Queen's University site has exceeded its enrollment quota to date for RCT #2. The interstitial cystitis research group is closely affiliated with the Queen's University Prostatitis Research Group (PI Dr. J.C. Nickel)

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which is collaborating in the NIH CPCRN (including CPCRN RCT#1). The Prostatitis research center is also meeting its recruitment quota in RCT#1. To our knowledge the Queen's University Prostatitis Research Center has initiated more prostatitis treatment trials and has enrolled more patients than any such research group worldwide. This application describes our aim to participate in the proposed NIH ICCRN as well as the proposed urological chronic pelvic pain syndromes collaborative group (UCPPSCG). Our group is proposing a clinically relevant definition of the urologic chronic pelvic pain syndromes encompassing both IC and male CPPS. This definition, based on chronic genito-urinary pain/discomfort with subcategories for urinary frequency urgency and no urinary frequency urgency will, if adopted by the UCPPSCG, facilitate decisions on treatments to be evaluated and increase the accrual rate of study participants in both IC and CPPS. We develop a rationale, hypothesis, objectives necessary to propose a 16 week randomized placebo controlled clinical trial (employing 2X2 factorial design) to evaluate the efficacy and safety of amitriptyline and gabapentin for the amelioration of symptoms in patients with a clinical diagnosis of IC. The Queen's University. site with Dr. Nickel as PI has the experience, expertise and the proven ability to design, implement and enroll patients with IC in clinical strudies and will be a valuable partner in the proposed ICCRN and UCPPSCG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK (ICCRN) Principal Investigator & Institution: Hanno, Phillip M.; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): This is an application from the Division of Urology of the University of Pennsylvania Health System (UPHS) to participate as a clinical site for the Interstitial Cystitis Clinical Research Network (ICCRN). The UPHS clinical site encompasses the core group of highly talented and experienced investigators who worked as a part of the Interstitial Cystitis Data Base Study and in the Interstitial Cystitis Clinical Trials Group (ICCTG), currently in its 5th year. The Div of Urology of the UPHS and the Univ of Pennsylvania has demonstrated their support and commitment to research on IC by actively participating in ICCTG #1 and #2. The Division of Urology of the UPHS Center, supports the broad research goals of the NIDDK with regard to interstitial cystitis (IC) and related disorders, through the following specific aims: Aim 1: To maintain our IC clinical network pertaining to all aspects of patient care, including recruiting and retaining patients with an appropriate age, race, and gender representation; providing high quality care; monitoring and ensuring safety; and coaching and encouraging subjects to be compliant with study protocols. Aim 2: To collaborate and provide scientific expertise on IC in all phases of the clinical trials and associated basic science or clinical additions to the core studies to aid in the discovery of new ways to determine the etiology, most efficient diagnosis, and best treatments of IC. Aim 3: To conduct objective, controlled, scientifically validated studies in order to determine the overall utility and efficacy of a variety of novel therapies for IC. A Central component is to continuously review and refine entry criteria as well as outcome parameters as additional scientific evidence becomes available. Aim 4: To work together as part of the Urological Chronic Pelvic Pain Syndromes Collaborative Group (UCPPSCG) with the following goals: (1) to shorten the period of protocol development, (2) to collect common information to permit comparisons of the clinical characteristics of these two conditions, (3) to facilitate decisions on treatments to

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be evaluated, and (4) to increase the rate of accrual of study participants. Aim 5: To develop a suitable clinical definition of IC, a clinically and scientifically based assessment of where the disease falls in the spectrum of chronic pelvic pain, pelvic floor dysfunction, and prostatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK (ICCRN) Principal Investigator & Institution: Sant, Grannum R.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The objectives of this proposal are the initiation and development of the Interstitial Cystitis Clinical Research Network (ICCRN) and the performance of randomized controlled multicenter clinical trials for the treatment of interstitial cystitis (IC). These objectives will be achieved by: (a) development and design of medical treatment protocols for IC and a manual of operations in conjunction with a Steering Committee consisting of the Clinical Centers, the Data Coordinating Center and the NIDDK Project Scientist. (b) recruitment and retention of patients who meet agreed upon Clinical Trials entry criteria The Specific Aims of the proposal are: (a) to assess the therapeutic effectiveness of drug (approved, investigational, other) and non-drug treatment of IC in well-characterized cohorts of IC patients (newly diagnosed, chronic, minority populations) (b) to utilize validated and meaningful treatment outcome measures (eg., SF-36 health-related quality of life; the O'Leary-Sant Symptom/Problem Index, global response assessment (GRA) (c) recruitment of a minimum of 50 patients/year for 4 years (total 200 patients). The Principal Investigator (Dr. Grannum R. Sant, has a 20 year experience in the diagnosis and treatment of IC and has a large IC patient population within his clinical practice. (d) there will be an initial 12 month period of collaborative protocol/manual of operations development, followed by 48 months of patient recruitment with concurrent data analysis and reporting. (e) coordinate protocol development and clinical outcomes analyses with the Chronic Prostatitis Clinical Research Network (CPCRN) under the umbrella of the Urological Chronic Pain Syndromes Collaborative Network (UCPPSCG). The data obtained from these randomized controlled studies will define the effectiveness of various therapies for IC and improve the quality of life of patients suffering from IC. The collaboration with the UCPPSCG will better define the urological pelvic pain syndromes (male and female) and lead to better classification and treatment outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK (ICCRN) Principal Investigator & Institution: Kreder, Karl J.; Professor; Urology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The long-term objectives and specific aims of this proposal are to establish the University of Iowa Interstitial Cystitis Research Group as a clinical center in the Interstitial Cystitis Clinical Research Network (ICCRN). The purpose of this network is to establish a collaborative group of centers with expertise in pelvic pain and interstitial cystitis to conduct controlled clinical trials that will provide further understanding of interstitial cystitis. Additionally this network will participate

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in the Urologic-Chronic Pelvic Pain Syndromes Collaborative Group to conduct trials in chronic prostatitis. A concept protocol using low dose BCG and interferon-alpha(alpha) is included in this proposal. The recruitment, marketing and retention strategies outlined in the following sections will ensure enrollment of between four and six patients per month as well as maximize this center's ability to recruit minority populations. This center has all the clinical and laboratory support as stated in the protocol. The following sections outline innovative methods to recruit both male and female interstitial cystitis patients 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 Interstitial Cystitis Research Group to serve as a Clinical Center in the multiinstitutional Interstitial Cystitis Clinical Research Network (ICCRN). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERSTITIAL CYSTITIS PHASE II TRIALS Principal Investigator & Institution: Culkin, Daniel J.; Professor and Chair; Urology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2001; Project Start 10-MAY-1998; Project End 28-FEB-2003 Summary: (Abstract of the application) Interstitial cystitis is a disease, which may affect over a million residents of the United States. To date there is no known cure for interstitial cystitis and most treatments are palliative at best. The NIDDK Interstitial Cystitis Data Base project began accruing patients in 1993 and provided invaluable information as it relates to the natural history, symptom association with urodynamic findings, cystoscopic findings and demographic information. This information and data is in place and has set the ground work for the next step of developing clinical research centers to carry out evaluation of therapies for IC in a prospective randomized fashion. The OU Health Sciences Center commits all of its resources, both on its campus in Oklahoma City and its network of outreach clinics throughout rural Oklahoma to recruit 200 patients into clinical trials. These protocols will be devised and written by the Steering Committee. Because of the sexual preponderance of IC being greater than 10:1, a collaborative effort has been arranged with the Department of Gynecology to access referrals from them for recruitment to these clinical trials. The University of Oklahoma has been interested in the treatment, diagnosis and management of IC for over 15 years. The Department of Urology ha also participated in the ICDB study project since its inception. In continuation of these research interests, we are submitting two concept sheets to the Steering Committee for their consideration for clinical research trials The newest treatment for IC, which has received FDA approval is the use of pentosulfate (Elmiron). Although this has shown reported successes of 50-75% i some individuals, there has been a significantly delayed time to response. Another form of therapy is behavior modification or Abladder retraining." Usin biofeedback offers the opportunity for pelvic floor musculature relaxation, which can alleviate the pain associated with bladder distention and IC. This adjuvant therapy of biofeedback with Elmiron may provide earlier time to response and offer significant palliation of IC symptoms while the oral epithelial coating agent, i.e. pentosulfate, is taking effect. The second concept is a two armed study using intravesical heparin versus intravesical heparin plus a biweekly, 6 week course of biofeedback bladder training for behavior modification. Patients in both arms of the study will be monitored fo positive response for one year. Eligibility will be determined by the Steering Committee. Positive response will be determined as greater to or equal to 40% improvement in clinical symptoms. To

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evaluate the durability of the response, participants will be reevaluated with the same tools every other month either by personal visit or telephone follow up. Statistical considerations for the pilot study will be determined by the steering committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERSTITIAL CYSTITIS TREATMENT PROTOCOLS Principal Investigator & Institution: Wein, Alan J.; Chairman; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 10-MAY-1998; Project End 28-FEB-2003 Summary: (Abstract of the application) The specific objectives of this proposal are: 1) Study the safety and efficacy of various treatments for Interstitial Cystitis (I.C.); 2) Collect uniform demographic and diagnostic information on patients being evaluated and treated for interstitial Cystitis, before and after therapy; 3) Collect clinical samples (urine, blood), which relate to the specific treatment utilized; 4) Transmit data and send clinical results to a central Data Coordination Center for analysis. The overall goal of this proposal is to conduct double-blind, parallel, randomized controlled clinical trials to determine the safety and efficacy of oral and intravesical therapies for Interstitial Cystitis. L-Arginine orally) and Heparin (intravesically) were selected because they hav been reported as efficacious agents with minimal side effects in the treatment of I.C. symptoms. During phase one we will participate in steering Committee planning and development of study protocols and data instruments. Years two through five we will conduct clinical trials potentially in parallel. In conjunction with Dr. Philip Hanno (Chief of Urology, Division of Urology, Temple University, Philadelphia, PA) and Dr. Kristene Whitmore (Chief of Urology, Allegheny University/ Graduate, Philadelphia, PA), specific objective 2, 3, and 4 have been accomplished as part of our ongoing joint studies on Interstitial Cystitis. The Philadelphia team has demonstrated the ability to work together and form an exceptionally efficient network for I.C. patients across a large geographical area. This group's constant interaction creates a solid professional alignment that benefits patients from near and far. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LPS-PEPTIDE INTERACTION IN BLADDER INFLAMMATION Principal Investigator & Institution: Saban, Ricardo; Associate Professor; Physiology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2001; Project Start 29-SEP-1998; Project End 30-JUN-2002 Summary: Bladder inflammation is a common cause of severe discomfort and morbidity in patients. During bladder inflammation a bi-directional communication is established between nerves containing substance P (SP) and bladder mast cells. SP activates mast cells to release mediators. Reciprocally, mast cell products stimulate sensory nerves to release SP. This bi-directional communication creates a vicious cycle of bladder inflammation. In previous work, we reported that SP is spontaneously released within the bladder wall, activates neurokinin (NK) receptors, and is inactivated by peptidase such as neutral metalloendopeptidase (NEP). Nerve to mast cell communication is dramatically altered in the presence of urinary tract infection. E. coli endotoxin lipopolysaccharide (LPS) induces inflammation by activating mast cells and sensory nerves, and by decreasing NEP activity. The central hypothesis of this proposal is that, regardless of the cause (LPS, SP, or antigens), bladder inflammatory responses follow a common pathway which involves: activation of mast cells and sensory nerves, release of

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SP, activation of NK receptors, and modulation of NEP activity. Three specific aims are proposed to test these hypothesis. Aim I will investigate the role of NEP in cystitis using NEP knockout mice. Aim II will investigate the role of NK1 receptors in cystitis using NK1-R knockout mice. Aim III will determine the role of mast cells in cystitis using genetically mast cell-deficient mice. The role of the mast cells in bladder inflammation will be precisely defined by examining the response in mast cell deficient mice that have had their mast cell deficiency selectively repaired by the adoptive transfer of mast cells derived from the normal congenic and NK1-R knockout mice. These studies will identify and define the important mechanisms involved in bladder inflammation and provide new insights for developing treatment strategies for cystitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ADAPTATION OF UROPATHOGENIC BACTERIA Principal Investigator & Institution: Sokurenko, Evgeni V.; Assistant Professor; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The primary goal of this study is to characterize on a genomic scale the adaptive evolution of Escherichia coli clones in the course of long-term urinary tract infections (UTI), in particular, episodes of recurrent cystitis and UTI characterized by a shift between the asymptomatic and symptomatic state. The main hypothesis to be tested is that adaptive evolution of uropathogenic E. coli is among the key mechanisms underlying the shift from the acute form of UTIs to recurrent infection and from asymptomatic to symptomatic infection. Molecular adaptation of bacterial pathogens in the course of infection involves point mutations in structural or regulatory genes as well as deletion or duplication of whole genes or chromosomal regions. These pathogenicityadaptive mutations can confer a selective advantage by improving the ability of the bacteria to adhere to or invade the uroepithelium or evade host defenses. There is strong evidence from both published and our preliminary studies that E. coli undergoes pathogenicity-adaptive evolution in the course of recurrent or long-term UTI. The studies proposed here will expand our understanding of this phenomena to the genomic level by employing two novel technologies, high-density microarrays and a wholegenome mutation scan developed in our laboratory. Both of these technologies will be utilized to perform a comparative analysis of sequential or matching clones of E. coli that have been isolated from patients with long-term UTI or in a chronic animal model of UTI. We will also define how adaptive evolution of uropathogens affects their ability to bind and invade uroepithelial cells, resist cellular host defenses and colonize in a mouse model of UTI. We expect that the proposed studies will clarify the mechanisms of long-term adaptive evolution of uropathogenic E. coli and provide a basis for future studies directed at a detailed understanding of the molecular pathogenesis of persistent and recurrent UTIs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR BASIS OF E COLI ADHESINS IN BLADDER DISORDERS Principal Investigator & Institution: Hultgren, Scott J.; Professor; Molecular Microbiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2001 Summary: (Adapted from the Applicant's Abstract): Even though interstitial cystitis is not associated with ongoing bacterial infections, previous infections may predispose or

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account for this inflammatory condition of the bladder. Understanding the molecular basis of bladder infections caused by E. coli will provide important insight into the possible sequelae of these infections such as interstitial cystis and unveil novel therapeutic and preventative strategies. This proposal represents an intensive effort combining high powered genetics, biochemistry, crystallography, and high resolution electron microscopy with a relevant primate model of cystitis to identify the molecular basis of the factors that are critical in bacterial cystitis. The exact roles played by bacterial adhesive organelles, including P pili, type 1 pili and curli, in causing bladder disorders, will be studied by testing a panel of isogenic mutant derivatives of the uropathogenic strain DS17 to i) bind to human and monkey bladder tissue in situ and ii) cause cystitis in cynomolgus monkeys. Receptor analogues will be used as inhibitors to determine the molecular basis of the adhesin-receptor interaction. Human bladder tissue obtained from patients with either bacterial cystitis or interstitial cystitis and tissue from infected monkeys will also be subjected to special staining using anti-type 1, antiFimH, and anti-P, anti-PapG and anti-curli antisera to elucidate whether these adhesions are expressed in vivo by adherent microorganisms or possibly deposited on the bladder mucosa. The presence of these factors in interstitial cystitis tissue, or cross-reacting antigens, would suggest that bacterial infections may be a predisposing factor. Purified PapG and FimH adhesions will also be tested for their ability to confer protection against cystitis in the primate model. In order to definitively analyze the interactive surface of the adhesin molecule as it is presented to the host, the first three dimensional structure of a bacterial adhesin (FimH) will be determined. A thorough understanding of the structural basis of microbial attachment, its role in virulence, and the interactive surfaces of an adhesin that facilitate its interaction with host receptors will give us a broad understanding of this disease that primarily affects women and unveil strategies that can be developed to block the host-pathogen interaction and reveal relevant vaccine candidates that protect against infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PATHOGENESIS OF E COLI UTI Principal Investigator & Institution: Mobley, Harry L.; Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2002 Summary: Urinary tract infection is the most frequently diagnosed kidney and urologic disease and E. coli is by far the most common etiologic agent. Certain E. coli phenotypes such as P fimbriation and hemolysin production are found more frequently in strains isolated from the urine of patients with acute pyelonephritis and cystitis than in feces from normal individuals. Indeed, the expression of P fimbriae and hemolysin was long thought to explain the virulence of these strains in the urinary tract, yet mutation of these genes in our laboratory did not significantly diminish virulence in an experimental CBA mouse model of infection. Recently, defined blocks of DNA termed "pathogenicity islands" have been found in uropathogenic strains to carry genes not generally found in fecal strains. We have characterized, by cloning and nucleotide sequencing, a 60-kb pathogenicity island on the chromosome of uropathogenic E. coli CFT073, isolated from the blood and urine of a woman with acute pyelonephritis. Evidence has been obtained for a second PAI. Secreted proteins have also emerged as key elements in models of pathogenesis and are produced by this and other urovirulent strains in our strain collection. It is also likely that genes common to all E. coli also play some role in the pathogenesis of cystitis and acute pyelonephritis. We hypothesize that genes within pathogenicity islands, secreted proteins, modulation of type 1 fimbriae all contribute

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directly to the development and pathogenesis of ascending urinary tract infection. As specific aims, we propose: 1) To identify secreted proteins unique to uropathogenic strains of E. coli; 2) To evaluate putative virulence genes encoded by a pathogenicity island of uropathogenic E. coli CFT073; 3) To identify and characterize a second set of pathogenicity island sequences associated with uropathogenic E. coli CFT073; and 4) To determine the position (On-Off) of the fim invertible element that controls transcription of Type 1 fimbria genes during acute urinary tract infection caused by E. coli. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE CELLS MEDIATED GENE THERAPY FOR INCONTINENCE Principal Investigator & Institution: Chancellor, Michael B.; Professor; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2002 Summary: Urinary incontinence is a major health care problem in the United States. The NIDDK has recently convened a workshop to bring attention and foster research in this underserved area. This grant will explore and develop a novel and promising treatment of urinary incontinence. The investigators will explore in depth the role of cellular tissue engineering using myoblast and muscle derived cells as a treatment of stress urinary incontinence when injected into the urethra. In addition, myoblast injection may improve detrusor contractility when injected into the bladder wall. They will also develop cell mediated gene therapy for the lower urinary tract using autologous muscle derived cells. The investigators hypothesize that: 1. Myoblast injection can improve bladder and urethral smooth muscle function. 2. Autologous myoblast can be harvested and injected to achieve long-term success. 3. Cell mediated gene therapy using myoblasts transduced with trophic factors can further repair urinary tract muscle damage. 4. Myoblast engineered with adenovirus carrying the expression for nitric oxide synthase gene can increase NO release and improve inflammatory cystitis and reduce bladder outlet obstruction. This grant explores the frontier of tissue engineering and gene therapy for the treatment of urinary tract dysfunction. The investigators believe that this project has direct clinical utility in the near future. Based on their anticipated results, they propose to harvest autologous muscle derived stem cells by aspirating a very small amount of skeletal muscle from a patient's arm. Grow the muscle derived cells in culture and engineered these myoblasts with viruses carrying the expression of growth and trophic factors or nitric oxide synthase [sic]. The engineered myoblasts are then injected into the impaired urethra or bladder of that patient during a simple outpatient cystoscopic procedure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROGENIC PATHOGENESIS OF INTERSTITIAL CYSTITIS Principal Investigator & Institution: Pezzone, Michael A.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Chronic pelvic pain is a poorly understood but sufficiently debilitating clinical condition primarily affecting women. Few diagnostic and treatment options are available for this understudied patient population, which is estimated at 9.2 million in the United States. The causes of chronic pelvic pain are numerous but may involve gynecologic, urologic, gastrointestinal, musculoskeletal, neuronal, or psychological origins as well as combinations thereof. The urinary bladder and colorecmm are two of the larger pelvic organs thought to be affected primarily in

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these disorders, and thus, it is not surprising that interstitial cystitis (IC) and irritable bowel syndrome (IBS) are two of the commonest causes of chronic pelvic pain. The observed overlap of chronic pelvic pain disorders such as IC and IBS suggests a common underlying etiology or even cross-organ (neurogenic) sensitization. Using a newly developed rodent model for studying afferent-mediated interactions of the pelvic organs in the rat, we will investigate the hypothesis that chronic irritation of the distal colon may adversely influence and sensitize urinary bladder afferents leading to neurogenic cystitis and its associated physiologic sequelae. The studies proposed in this application will attempt to shed more light on the overlap and etiology of chronic pelvic pain syndromes and the role of cross-organ, afferent sensitization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROVASCULAR AND BEHAVORIAL RESPONSE TO CYSTITIS Principal Investigator & Institution: Bjorling, Dale E.; Professor and Chair; Surgical Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Interstitial Cystitis (IC) is a disorder of uncertain etiology that primarily results in increased supra-pubic pain and increased voiding frequency. Although IC often appears to develop in the wake of urinary tract infection (acute or repeated), the acute and chronic effects of urinary tract infection on bladder innervation, vasculature, and function have not been well characterized. Most studies of inflammatory cystitis in animal models have utilized chemically induced models of cystitis and focused on acute effects. There is a critical need to extend observations made on chemically induced cystitis to the effects of bacterial cystitis and to characterize the long-term effects of acute and chronic infectious cystitis. The proposed research will address the hypothesis that repeated urinary tract infection results in persistent changes in bladder innervation, vasculature, and function that contribute to symptoms of IC after the infection is apparently resolved. We will also address the corollary hypotheses that these changes may be mimicked by prolonged chemical cystitis induced by systemic administration of CYP and that susceptibility of mice to the durable the effects of inflammatory cystitis on bladder innervation, vasculature, and function vary among different strains of mice. The proposed research will use an integrated experimental approach and novel imaging techniques to characterize the cellular, histological, neurological, and behavioral response to bladder inflammation (acute and chronic) and determine whether changes persist after removal of the initiating stimulus. This research will investigate the durability of changes that occur in response to a common clinical problem and elucidate the ways in which a "simple UTr' may create a cascade of changes in the bladder physiology and function, neuroregulation, pain perception and behavior that underlie the complex clinical face of IC. The long range plan for this line of research is to link the information generated in the proposed study to future investigations into the genetic basis for variations in susceptibility to cystitis among strains of mice and how this relates to variability among humans regarding sensitivity to the effects of UTI and the occurrence of painful bladder disorders of uncertain etiology, such as IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NITRIC OXIDE TRANSDUCTION MECHANISMS IN UTIS AND IC Principal Investigator & Institution: Weiss, Robert M.; Professor and Chief; Surgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047

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Timing: Fiscal Year 2001; Project Start 30-SEP-1993; Project End 28-FEB-2003 Summary: (Adapted from the Applicant's Abstract): Urinary tract infections (UTIs) and interstitial cystitis (IC) are two pathologic conditions of the urinary system which predominately affect women and which have medical, psychological, sociological and economic implications. The unifying hypothesis of this proposal is that nitric oxide (NO), a small lipophilic gaseous molecule, which is released from non-adrenergic, noncholinergic neurons and which is synthesized in a variety of mammalian tissues including macrophages and neutrophils, acts as a mediator in UTIs and IC. The applicants have: 1) shown that nitric oxide synthase (NOS) activity and cyclic GMP levels are elevated in the urine of patients with a UTI and decreased in the urine of patients with IC; 2) providing the first definitive molecular evidence for the presence of a biologically active inducible NOS (iNOS) in human neutrophils during an infectious process; and 3) shown that L-arginine administration to IC patients increases NOS activity and urinary cyclic GMP and Nox (nitrate plus nitrite) levels, and results in a decrease in IC related symptoms. To test their hypothesis they plan to: 1) determine factors, including cytokines and bacterial products, that mediate the production of nitric oxide in isolated human neutrophils, and to determine if and how neutrophil produced NO is involved in phagocytosis and bacterial killing; 2) identify the inflammatory agents, i.e., bacterial products and cytokines, enzymatic reactions, and cell types, that are involved in the induction of NOS during the initiation of and reparative response to inflammatory/infectious processes in the urinary tract; 3) characterize the subcellular localization and the post translational modifications that regulate human iNOS (hiNOS) expression using an in vitro heterologous system; and 4) determine the relationship between inflammatory cell identity, nitric oxide, prostaglandin and cytokine production, and IC related symptoms. The interpretation of the data obtained will not only pertain to infectious/inflammatory processes of he urinary tract, but also will facilitate the understanding of processes in humans which are less amenable to investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NONINVASIVE DETECTION OF UROTHELIAL ABNORMALITIES Principal Investigator & Institution: Pan, Yingtian; Assistant Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 31-DEC-2003 Summary: (Adapted from the Applicant's Abstract): This research proposes to apply a novel imaging technology, high fidelity cystoscopic optical coherence tomography (OCT), to image micro-morphology of urinary bladder and to detect urothelial abnormalities (e.g. tumors). Advanced imaging techniques (e.g., fiber-optic Mach Zehnder interferometry, confocal microscopy, polarization detection and electrooptic scanning) will be used, thus allowing imaging diagnosis of bladder lesions in vivo, noinvasively, immediately and at high fidelity. Rat bladder will be imaged ex vivo and compared with histological evaluation to systematically analyze the morphological and physiological changes occurring during the methyl nitrosourea (MNU) induced tumor formation. Porcine bladder will be imaged ex vivo to compare mammalian bladders; normal procine bladder and cat bladder with iterstitial cystitis will be imaged in vivo to test the development of a cystoscopic OCT system. Most bladder cancers (e.g., carcinoma in situ) are treatable (if not curable), if diagnosed prior to metastasis and treated appropriately. Endoscopic visual inspection of surface lesions is presently the clinical standard, and conclusive diagnosis and staging of malignancy relies on surgical biopsy and histological examination. This results in an enormous number of negative biopsies of benign bladder lesions with their attendant risks and complications.

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Therefore, a noninvasive imaging technique is needed that allows early ultrasound and convential endoscopy, are inadequate, either because of poor resolution and limited penetration or technical imperfection. OCT, a new technology, allows noninvasive visualization of vertical cross-sectional micro-morphology (10 mum resolution) at depths of 1-3 mm beneath the bladder surface. Our preliminary results have clearly demonstrated the potential value to provide clinicians with rapid, noninvasive diagnosis of abnormalities. No other technique offers this potential at present. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: P4: SEX DIFFERENCES IN CRF, NORADRENERGIC FUNCTION AND OXYTOCIN IN CATS WITH IC Principal Investigator & Institution: Buffington, Charles A.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The long-term goal is to exploit a naturally occurring bladder disease in domestic cats (Feline Interstitial Cystitis - FIC) to gain a better understanding of a painful bladder disorder in humans called interstitial cystitis (IC), and by extension other pelvic pain syndromes. This is because many patients with IC also have IBS and other neurovisceral disorders that predominantly affect women, and appear to be exacerbated by stress. The studies proposed here are designed to further investigate the causes of these neurological alterations in controlled studies of cats diagnosed with IC and healthy cats. The studies are needed to elucidate the significance of the underlying neurological abnormalities present in human patients with IC. They also are intended to guide the choice of subsequent studies toward the primary systems involved in IC, with the eventual goal of identifying rational treatments of IC in human beings. The overall objective of this proposal is to test the hypothesis that interactions between CRF, sex hormones and the alpha-2 adrenoceptor (alpha2-AR) play a role in the sex difference in stress-responsiveness of cats with FIC. The rationale for the proposal is based on 1) clinical evidence that females are more prone to develop IC than males (intact males in cats), 2) the gap in knowledge in factors that may account for such sex differences due to the paucity of experimental data in this field, 3) evidence from our recent studies pointing to a role of alpha2-AR dysfunction in cats with IC, and 4) existing evidence that urothelial and alpha2-AR function can be modulated by testosterone, estrogen, and oxytocin. By studying a natural occurring animal model of IC which shares many features with a rat model of IBS, and with the respective human patient populations, we will be able to assess the role of sex hormones on the expression of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PACAP OVEREXPRESSION AND VOIDING FUNCTION Principal Investigator & Institution: Schwarz, Edward M.; Associate Professor; Orthopaedics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Interstitial Cystitis (IC) is a chronic irritative voiding syndrome that occurs without objective evidence of disease and is characterized by urinary frequency, nocturia, urgency, suprapubic pressure, and bladder or pelvic pain. The etiology(s) is currently unknown, and there are no reliably effective treatments. Many patients are left to suffer for the rest of their lives with this incapacitating condition. We hypothesize that IC develops when a barrier defect induces the expression of neuropeptides that transmit signals in the central nervous system (CNS),

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establishing the neuropathological hallmarks of the disease. Pituitary adenylate cyclaseactivating polypeptide (PACAP) is a leading candidate neuropeptide in the regulation of bladder function and upregulates in bladder afferent cells in the dorsal root ganglia (DRG) in cystitis models. It has been demonstrated recently that PACAP antagonists delivered intrathecally or intravesically can improve bladder overactivity in rodents with cystitis. Here we propose to develop two transgenic mouse models of PACAP over-expression in a tissue-specific manner to evaluate the role of this factor in the neurotrophic mechanisms and lower urinary tract plasticity associated with cystitis. These mouse models will have broad appeal to address not only PACAP's contribution to micturition reflexes, but also PACAP's role in nociceptive mechanisms in general. In a somatic mosaic model, PACAP38 will be over-expressed selectively in bladder sensory neurons following a direct bladder wall injection of a recombinant retrovirus that expresses the cDNA from the neuronal enolase specific promoter. We will also make mice that harbor a PACAP38 transgene whose transcription is controlled by a tetracycline-inducible promoter. These mice (TREPACAP38) will be crossed with our UPII-rtTA transgenic mice that express the reverse tetracycline transactivator only in urothelial cells. These bitransgenic mice (Uro-TetON-PACAP38) will receive doxycycline in their drinking water to evaluate the effect of drug-inducible PACAP over-expression in the bladder. Initial studies to validate the in vivo expression of PACAP38 and its effects on voiding function will be performed. If successful, the mice will be distributed to interested labs to assist with the rigorous characterization of the models as they relate to the neurochemical organization of voiding function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PAIN AND INTERSTITIAL CYSTITIS Principal Investigator & Institution: Wesselmann, Ursula; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Interstitial cystitis (IC) is a chronic bladder disease characterized by urinary frequency/urgency and suprapubic pain. There are currently no consistently effective treatments for IC available. The long-range objective of this research is to develop a better understanding of the pathophysiological mechanisms of the pain aspects of IC, in order to develop improved treatment strategies. Clinical, immunologic and neurobiologic characteristics all support the hypothesis that IC is a heterogeneous syndrome. The proposed studies are based on two clinical observations: First, IC shares many characteristics with other chronic visceral pain syndromes. In addition, many patients with IC report extra-bladder pain symptoms, such as gastrointestinal, pelvic and chronic somatic pain. This clinical impression has been confirmed by a series of epidemiological studies. These observations suggest that there might be generalized alterations in pain modulatory mechanisms in IC. Second, IC affects predominantly women in their reproductive ages. This observation suggests that the proposed alterations in nociceptive processing in IC might be further modulated by the gonadal hormonal milieu. The working hypotheses for this proposal are that (1) a spectrum of different insults can lead to chronic pain in patients suffering from IC, (2) different underlying pathogenic pain mechanisms may require different treatment strategies for patients diagnosed with IC, (3) multiple different pathogenic pain mechanisms may coexist in the same patient. The following aims address these hypotheses: Aim 1: We propose to characterize patients with IC in detail using neurophysiological (measures of nociceptive function), autonomic and psychological

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parameters, urine markers of bladder epithelial function and cytokine profiles (urine, blood). Aim 2: We will determine the influence of the gonadal hormonal milieu on symptoms of the disease in women with IC. We expect that patients with IC can be differentiated into distinct sub-groups, based on the parameters tested. The results of these studies should have rapid clinical implications: if subsets of patients with different IC etiologies can be identified, then they can be targeted for focused research and specific treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PAIN SENSITIVITY AND MENSTRUAL CYCLE EFFECTS IN IC Principal Investigator & Institution: Fillingim, Roger B.; Associate Professor; Operative Dentistry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Interstitial cystitis (IC) is a sterile bladder condition of unknown etiology characterized by increased urinary urgency and frequency as well as suprapubic pain. Two important features of the disorder that must be explained are that: 1) IC affects predominantly females, and 2) IC patients exhibit enhanced sensitivity to bladder distention. In addition, clinical observation suggests that symptoms of IC are exacerbated perimenstrually. The research proposed in this exploratory/developmental (R21) grant application is based on the overriding hypothesis that these clinical features can, at least in part, be explained by a generalized alteration in central nervous system nociceptive processing in IC, which is influenced by the hormonal fluctuations that accompany the female menstrual cycle. Based on this hypothesis two predictions regarding IC will be investigated: first, that IC is associated with a generalized increase in pain sensitivity, which includes enhanced responses to somatic as well as visceral stimuli; and second, that both clinical symptoms and responses to experimentallyevoked pain will be influenced by the menstrual cycle in IC patients. In order to examine these predictions, the responses of IC patients and healthy, female controls to three clinically relevant laboratory pain induction procedures will be evaluated: a) temporal summation of thermal pain, b) ischemic arm pain, and c) visceral pain produced by fluid distention of the urinary bladder. In addition, clinical symptoms as well as responses to the same three experimental pain procedures will be assessed across the menstrual cycle in both IC patients and controls. It is anticipated that: 1) IC patients will demonstrate greater sensitivity to both somatic and visceral pain stimuli relative to controls; 2) clinical symptoms will be greater among IC patients during the luteal versus the follicular phase of the menstrual cycle, while menstrual cycle effects on clinical symptoms among controls will be minimal; and 3) experimental pain sensitivity for both groups will be greater during the luteal versus the follicular phase; however, the menstrual cycle effect will be greater for IC patients than controls. The results of this research will provide important and novel information regarding pain sensitivity and menstrual cycle effects in IC and will establish a foundation of knowledge to support more extensive investigations of hormonal influences on nociceptive processing in interstitial cystitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF SV40 INFECTIONS IN MACAQUES W/ AIDS Principal Investigator & Institution: Simon, Meredith A.; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001

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Summary: The primate polyomaviruses include JCV and BKV, which infect humans, and the closely related SV40 of macaques In immunocompetent hosts, primary infection occurs early in life, with mild or absent clinical signs The virus then persists as a latent infection mainly in kidney Reactivation with viral shedding can occur with pregnancy, chronic diseases or immunocompromise, and may or may not be associated with clinical signs JCV is associated with progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS) due to infection of oligodendrocytes, in up to 5% of AIDS patients BKV causes interstitial nephritis and/or hemorrhagic cystitis, particularly in transplant recipients Similarly, SV40 is associated with both PML and nephritis in SIV-infected macaques with simian AIDS Previous studies indicated that SV40 causes interstitial nephritis in primary infections, and PML upon reactivation of a latent infection in SIV-infected macaques We now recognize a second CNS manifestation of SV40 a meningoencephalitis affecting cerebral gray matter, without demyelination, distinct from PML This lesion can be a primary manifestation of SV40 in conjunction with SV40-induced interstitial nephritis In situ hybridization for SV40, coupled with immunohistochemistry for glial fibrillary acidic protein on the same section, demonstrates that many of the infected cells in the meningoencephalitic lesions are astrocytes, in contrast to PML, where the majority of infected cells are oligodendrocytes Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENIC MECHANISMS IN URINARY TRACT INFECTION Principal Investigator & Institution: Stamm, Walter E.; Professor; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 24-FEB-1998; Project End 30-JUN-2008 Summary: An estimated 150 million UTIs occur annually on a global basis, accounting for direct health care costs exceeding 6 billion dollars and making UTIs a very significant public health burden. This program project proposes studies that will improve our understanding of the epidemiology, microbial ecology, molecular pathogenesis and prevention of UTIs. The objectives of the project will be met through the development of a multidisciplinary research team that will collaborate to carry out four interrelated projects. Project 1 will undertake a double-blind placebo-controlled trial to determine whether a Lactobacillus crispatis vaginal probiotic will reduce the incidence of recurrent UTIs in women. The trial will also study adherence of the probiotic strain to vaginal epithelial cells from the subjects and will thus provide insight into the host and microbial mechanisms involved. Project 2 will address the hypothesis that cell surface glycosphingolipids in the bladder and vaginal epithelium are structurally organized into pleotrophic plasma membrane assemblies called caveolae and that caveolae participate in the initial epithelial response to attachment and uptake of uropathogenic e. coil Project 3 will employ two novel technologies that were developed during the previous funding period, namely high density microarrays and whole genome mutation scanning to characterize on a genomic level the molecular adaptation that uropathogenic E. coil strains undergo in the course of recurrent UTIs and in shifting from an asymptomatic to symptomatic infection. The project will also define how such adaptive evolution affects the ability of uropathogens to bind and invade epithelial cells, induce inflammation and resist phagocytosis. In Project 4, the association of host susceptibility to recurrent cystitis or pyelonephritis with known or novel mutations in specifically selected candidate host genes will be examined. The candidate genes to be studied are toll-like receptors (TLR2, TLR4, and TLR6), chemokine receptors (CXCRI and CXCR2), and interferon y receptors (IFN-yR1 and IFN-yR2). A

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laboratory core will provide microbiological studies, primary bladder and vaginal epithelial cells, characterization of urovirulence genes, bacterial adherence assays and other resources to the projects. An Administrative/Biostatistical Core will coordinate the overall project and provide biostatistical expertise to all investigators. The proposed studies will result in an improved understanding of pathogenetic mechanisms in UTIs and will result in new approaches to prevention of UTIs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENICITY OF PROTEUS MIRABILIS METALLOPROTEASES Principal Investigator & Institution: Belas, M Robert.; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001 Summary: Proteus mirabilis represents only a small percentage of the bacteria for causing uncomplicated cystitis or acute pyelonephritis in the normal host, but its importance in UT1 is underscored when the incidences of infection in patients with complicated urinary tracts, i.e., those with functional or anatomic abnormalities or with chronic instrumentation, are examined. In these cases, P. mirabilis is a more frequent uropathogen and its infection may be more severe due to the formation of urinary stones caused by the breakdown of urea by urease. Urease and a set of other virulence factors, including flagella and a IgA-degrading metalloprotease (ZapA), are coordinately regulated as part of a cycle of cellular differentiation and behavior known as swarming. For this reason, it has been postulated that a swarmer cell differentiation and swarming behavior are important in P. mirabilis virulence and UTI. We have identified two metalloproteases: ZapA and ZapE. ZapA is an important virulence factor of P. mirabilis, as we have shown by comparing the survival of ZapA-mutants with the isogenic wild type strain during UTI. The function of os not known, however its amino acid sequence suggests that ZapE may function either as a cytolysin or hemolysin. While it is not known that ZapA has the ability to degrade host immunoglobulins, the dramatic attenuation of virulence in strains lacking ZapA suggests that ZapA and ZapE may have a broader spectrum of activity associated with virulence. This project proposes to test the hypothesis that the roles of ZapA and ZapE in UTI extend beyond cleavage of IgA and IgG, and that the principal substrates of these metalloproteases are other proteins found in the urinary tract, specifically epithelial cell membrane proteins. To test this hypothesis, a panel of proteins consisting of cytoskeletal and extracellular cell matrix proteins of urinary epithelial cells, as well as proteins involved in the host defense mechanism, will be tested as potential substrates for metalloproteases. The activity of each protease will be assessed using (1) purified protein substrates, (1) bladder and kidney epithelial cell cultures, and (3) in our mouse model of UTI, in which the in vivo effects of proteolysis on bladder and kidneys will be measured. For these experiments, we will isolate and purify each protease and construct isogenic mutants lacking either or both protease-encoding genes. As a Specific Aim, we propose: 1. To characterize the role of the ZapA and putative ZapE metalloproteinases in UTI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERMEABILITY BARRIER OF MAMMALIAN BLADDER Principal Investigator & Institution: Zeidel, Mark L.; Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1993; Project End 31-AUG-2002

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Summary: In several forms of bladder injury, loss of epithelial barrier function is associated with failure of normal filling and emptying function, so that frequency, urgency/incontinence, and pain occur. Millions of people suffer these symptoms each year, ranging in duration from brief episodes in young women with bacterial cystitis, to chronic symptomatology of waxing and waning severity in patients with interstitial cystitis, to chronic severe dysfunction in patients suffering the effects of radiation cystitis and hemorrhagic cystitis due to cyclophosphamide therapy. At present, almost nothing is known about the mechanisms of bladder epithelial damage and the effects of failure of the bladder permeability barrier on the underlying muscle and nerves. The proposed experiments will examine the mechanisms of bladder epithelial damage in two models of cystitis and will determine how acute loss of epithelial barrier integrity affects the function of bladder muscle and afferent nerves. In the first funding period, we provided the first quantitative analysis of the permeability properties of the bladder permeability barrier and developed a preliminary understanding of the trafficking mechanisms responsible for changing the surface area of the apical membrane in response to bladder filling and emptying. In addition, they developed from reconstituted bilayers a model of how the apical membrane is structured to function as a barrier. Using models of barrier injury derived directly from the first funding period, this competing renewal application has three specific aims. In Aim #1, rabbit bladder epithelium will be subjected to ischemic injury in the Ussing chamber. Initial studies will define the ability of the epithelium to recover from the injury. Next, the effects of ischemia on the determinants of barrier function (the tight junctions, the apical membrane and the mechanisms for trafficking of membrane into and out of the apical surface) as well as other cell structures and activities critical to barrier function (energy generation and the cytoskeleton) will be defined. In Aim #2, bladders of guinea pigs sensitized to ovalbumin will be exposed to apical ovalbumin, leading to inflammation of the bladder wall. Initial studies will define in detail the time course of loss of barrier function and its recovery in this model. Subsequent studies will define the effects of bladder inflammation on the determinants of barrier function and their supporting structures and activities, as well as the role of specific mediators in epithelial injury. In Aim #3, the permeability barriers of rat bladders will be disrupted in situ with protamine sulfate and the effects of the resulting leakage of urinary constituents on the function of the underlying bladder muscle and the activity of bladder afferents will be determined. The proposed studies will provide the first mechanistic examination of the failure of the bladder permeability barrier in ischemic and inflammatory injury, and will determine directly whether leakage of urinary constituents per se leads to dysfunction of the underlying musculature and increase in afferent nerve traffic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PLA2 ACTIVATION BY MAST CELL TRYPTASE IN IC Principal Investigator & Institution: Mchowat, Jane G.; Associate Professor; Pathology; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Interstitial cystitis (IC) is an inflammatory bladder condition with unknown etiology, although a defect in bladder cytoprotection by the urothelium and a pathophysiologic role for the mast cell has been implicated. We hypothesize that these two processes participate in a vicious cycle of inflammation, with tryptase released from activated mast cells activating the protease-activated receptor-2 (PAR-2) on urothelial and endothelial cells in the bladder and resulting in increased phospholipase A2 (PLA2) activity and accelerated production of inflammatory

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phospholipid metabolites such as eicosanoids and platelet activating factor (PAF). Additionally, mast cell tryptase may contribute to exacerbation of inflammation directly or indirectly by increasing the permeability of the urothelium leading to increased movement of urinary contents into the bladder wall and by increasing endothelial cell permeability and adhesion of polymorphonuclear leukocytes (PMNs) to the endothelium, resulting in increased PMN content in the bladder wall. The specific aims to test this hypothesis are: 1. To determine whether tryptase stimulation of human urothelial (HUR) cells contributes to the propagation of the inflammatory process by increasing PLA2 activity and production of inflammatory mediators, such as eicosanoids and PAF. Changes in urothelial cell permeability and resistance and the rate of wound healing in the urothelium will also be measured in the presence and absence of tryptase to determine the effect of tryptase on the barrier function of the urothelium. 2. To determine whether tryptase stimulation of human bladder microvascular endothelial cells contributes to the propagation of the inflammatory process by measuring PLA2 activity and phospholipid-derived inflammatory mediators in response to tryptase. Endothelial cell permeability, increased expression of cell surface adhesion molecules and increased PMN adherence to the endothelial cell monolayer will determine if tryptase contributes to PMN recruitment to the bladder. These studies will provide an understanding of the role of mast cells in the propagation of inflammation in the bladder in such conditions as IC and highlight possible avenues for pharmacological intervention to alleviate the debilitating symptoms of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMIC CHARACTERIZATION OF IC BLADDER Principal Investigator & Institution: De Miguel, Fernando; Urology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Interstitial cystitis (IC) is a painful bladder syndrome of unknown etiology, characterized by chronic pelvic pain, urinary frequency and urgency. It affects an estimated 700,000 to one million people in the United States; approximately 90% of the reported sufferers are women. Diagnosis of IC is primarily based on symptoms, as there are no currently available blood or urine tests due to the lack of demonstrated biological markers. The nuclear matrix is the structural scaffolding of the cell nucleus and plays a central role in the regulation of important cellular processes. Specific nuclear matrix proteins (NMPs) have been identified as unique to certain cell types or states. Although the estimated number of different proteins in a cell might outnumber the estimated number of genes in the same cell, proteins are the functional players in cell pathophysiology. Therefore, we propose to use a proteomic approach to identify specific new markers related to chronic cystitis. Several agents, such as Nerve Growth Factor (NGF), nitric oxide (NO) and proinflammatory mediators, have been shown to exert an effect in bladder afferent pathways that could be related to frequent voiding and nociceptive responses in chronic cystitis. Thus, two hypotheses will be tested: 1) Alterations in NMPs are characteristic of the bladder with chronic irritation and can be developed into diagnostic markers and/or treatment targets for painful bladder syndrome such as IC. 2) Functional improvement of chronic cystitis after intervention on NGF, NO, and inflammatory pathways, is associated with changes in NMPs. To address these hypotheses, we propose the following Specific Aims: 1) to perform a comprehensive analysis of the nuclear matrix protein composition of the bladder with chronic irritation in comparison to normal controls to identify specific proteins associated with the disease. 2) to characterize and sequence specific nuclear

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matrix proteins associated with bladders with chronic irritation and to raise antibodies against these markers and to develop diagnostics tests in this regard. 3) to analyze the effect of several modulators of the bladder afferent pathway, NGF, NO and IPD-1151 T, on specific NMPs associated with the pathogenesis of chronic cystitic bladder. The longterm objectives of this research project are to identify new markers that can be used in sensitive, specific test/screens for IC and may prove of immense value in the accurate diagnosis, and even early prediction, of disease. The results of this research project could also identify new molecular targets of drug therapy for chronic bladder and/or pelvic pain associated with painful bladder syndromes, offering a better outcome for patients with IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS APPROACHES TO INTERSTITIAL CYSTITIS. Principal Investigator & Institution: Liu, Brian C.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): This application is in response to a Request for Applications (RFA): DK-03-010, Basic Research in Interstitial Cystitis. Diagnosis of interstitial cystitis (IC) is primarily based on symptoms, as there are no currently available blood or urine tests due to the lack of demonstrated biological markers. In addition, there are currently no consistently effective treatments for IC, and a precise etiology has not been demonstrated. Thus, one area of critical need is to identify disease markers for IC. Markers that can be used in sensitive, specific tests/screens for IC may have immense value in the accurate diagnosis of disease, as well as elucidating potential pathobiological pathways that may translate into a mode of action for the treatment of IC. The identification of disease signatures is one of the research areas of special interest, and anticipated goals of this RFA. Therefore, to fulfill this goal, we will: 1) generate disease-associated urinary protein profiles of clinically annotated interstitial cystitis specimens with surface enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry; 2) characterize potential disease-associated proteins, based on results obtained from SELDI-TOF, by 2-0 difference gel electrophoresis (2-D QIGE) and tandem mass spectrometry (msims)-based sequence identification; 3) compare relative expression levels of low- abundance urinary proteins in clinically annotated IC specimens with isotope-coded affinity tag (ICAT) and mass spectrometry; 4) mine proteomics data and to create predictive bioinformatics models (i.e., hierarchical cluster analysis and K-means methods, canonical correlations, discriminant analysis, Bayesian statistics, self-organizing maps and neural networks) that can stratify samples according to clinical information and/or outcome; 5) develop a biorepository consisting of urine, serum, and plasma specimens as a resource for future assays, including the creation of resources in the form of frozen urine, serum, and plasma protein arrays, as well as resources for global metabolomics studies. Through these specific aims, our goal is to fulfill the need to develop reliable predictive and diagnostic tools for IC, which is deemed to be a high-priority by the NIDDK Bladder Research Progress Group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUANTITATIVE STUDY OF URINARY BLADDER SENSORY PROCESSING Principal Investigator & Institution: Ness, Timothy J.; Associate Professor; Anesthesiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294

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Timing: Fiscal Year 2001; Project Start 25-JUL-1997; Project End 31-MAY-2002 Summary: Acute and chronic pains originating from the urinary bladder are common clinincal entities. Some conditions are easy to treat, but others such as interstitial cystitis have proved resistant to diagnosis and treatment. Interstitial cystitis can be described as a visceral neuropathic pain, a hypersensitivity state that is secondary to a site of irritation (a peripheral generator) located in the urinary bladder. It has been estimated to afflict 90,000-450,000 Americans, mainly women. Frustrated and at a loss for effective treatments, some patients have undergone surgical removal of their bladders, only to have continued pain. Attempts to understand and treat this disorder have examined the peripheral generator. This application proposes to extend our field of interest to the spinal sites of sensory processing which may magnify and prolong the effects of peripheral processes. The hypothesis central to the proposed studies is the following: Urinary bladder pain occurs secondary to a N-methyl-D-aspartate glutamate receptormediated, spinal, sensitization process produced by repeated or continuous primary afferent activation which leads to a hypersensitivity state in which previously innocuous stimuli produce pain. To test the critical elements of this hypothesis, the elements of spinal visceral nociceptive processing will be defined in halothane- anesthetized, female rats utilizing methodology developed in studies of gut sensation. Studies of primary afferent nerve pathways and physiologic responses in the rat will generate necessary parallel information that will allow for proper interpretation of spinal neuronal data. Neuronal and physiologic responses to urinary bladder distension will also be examined in rats receiving manipulations demonstrated to produce hypersensitivity (inflammation) or prevent hypersensitivity (N- methyl-D-aspartate receptor antagonists) in other model systems. The quantitative studies or urinary bladder sensation proposed in this grant application will test a hypothetical model of visceral nociception and will assess whether a novel group of analgesics, the N-methyl-D-aspartate glutamate receptor antagonists, may have efficacy in the treatment of visceral hypersensitivity states such as interstitial cystitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGENERATION OF FUNCTIONAL SMOOTH MUSCLE TISSUE Principal Investigator & Institution: Tanagho, Emil A.; Professor; Urology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 31-DEC-2004 Summary: (Adapted from the Applicant's Abstract): The long-term objective of this proposal is to investigate the cellular and molecular mechanisms of growth factors mediated regeneration of acellular bladder matrix using both in vitro and in vivo models and its potential clinical use. The hypothesis is that growth factors (TGFb1, EGF, KGF and VEGF) will stimulate the process of regeneration of acellular matrix bladder when grafted to the host bladder (normal, diabetic and interstitial cystitis) after partial cystectomy. These growth factors will stimulate the process of ingrowth of smooth muscle, urothelial lining, vascularization and innervation in the regeneration of new functional bladder. Specific Aim # 1. Effects of growth factors (TGFb1, EGF, KGF and VEGF) on regeneration of bladder morphology and growth using normal and diseased bladder. Under this specific aim, the investigators will test the hypothesis that growth factors will stimulate the process of regeneration of acellular matrix bladder when grafted to the host bladder (normal and diseased such as diabetic and interstitial cystitis) after partial cystectomy. To test this hypothesis following experiments will be conducted: (a). Effects of growth factors on epithelial migration and growth in normal and diseased bladder. (b). Effects of growth factors on smooth muscle cells migration

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and growth in normal and diseased bladder. (c). Effects of growth factors on invasion of blood vessels and nerves in normal and diseased bladder. Specific Aim # 2. Functional studies of matrix-directed regenerated bladders in normal and diseased hosts treated with growth factors. Under this specific aim, they will test the hypothesis that the augmented bladder after acellular matrix grafting in normal and diseased hosts (diabetic and interstitial cystitis) will be re-innervated with cholinergic and adrenergic nerve fibers and perform normal voiding function through their receptors. To test this hypothesis, following experiments will be done: (a). In vivo bladder functional studies by micturition pattern. (b). In vitro bladder functional studies by tissue bath experiments. (c). Immunochemical studies of adrenergic and cholinergic nerves of regenerated bladder. Specific Aim # 3. Cellular and molecular mechanisms of growth factor-induced and matrix directed bladder regeneration in normal and diseased hosts. Under this specific aim, they will test the hypothesis that gene and protein expression of growth factors (TGFb1, EGF, KGF and VEGF) will enhance reepithelization, vascularization and innervation of matrix-directed bladder regeneration in normal and diseased hosts (diabetic and interstitial cystitis). To test this hypothesis, following experiments will be done: (a). To analyze gene expression of growth factor TGFb1, EGF, KGF and VEGF in host and regenerated bladder.; (b). To analyze protein expression and localization of growth factors TGFb1, EGF, KGF and VEGF in host and re-generated bladder. (c). To analyze gene and protein expression of receptors for growth factors TGFb1, EGF, KGF and VEGF in host and re-generated bladder. Specific Aim # 4. Clinical application of matrix-directed bladder regeneration. The investigators will initiate clinical trials for bladder augmentation and urethral stricture repair using organ specific acellular matrix. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATON OF UROTHELIAL GROWTH Principal Investigator & Institution: Sun, Tung-Tien H.; Professor; Dermatology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The luminal surface of the entire lower urinary tract including renal pelvis, ureter, bladder and proximal urethra is lined by a cell type described in standard textbooks as the transitional epithelium or urothelium, which is characterized by a highly specialized apical cell surface covered by rigid-looking urothelial plaques consisting of hexagonally packed 16 nm uroplakin particles. It has been suggested that urothelial defects can result in a loss of the permeability barrier function allowing the penetration of some urine irritants into the bladder wall thus causing pain in interstitial cystitis. In addition, it is generally assumed that urothelial cells lining the different portions of the urinary tract are the same; hence conclusions derived from studying cells of one region should be applicable to all urothelial cells. However, urothelia of renal pelvis/ureter/trigone are known to have a different embryological origin than urothelial cells of other sites, and there are indications that urothelium is biochemically heterogeneous. In this project, we will (i) determine whether the urothelia that cover renal pelvis, ureter, bladder, and proximal urethra actually consist of several distinct cell lineages by analyzing the relative contributions of intrinsic divergence vs. extrinsic modulation to urothelial phenotypes, and (ii) identify the stem cells in various urothelial compartments using cell kinetic, cell culture and stem cell transplantation techniques. These proposed studies can yield important information because if urothelium indeed can be separated into several distinct subpopulations belonging to different cell lineages, one needs to re-examine the validity of some earlier

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studies in which urothelial cells from different parts of the urinary tract were used interchangeably. Since stem cells are the preferred targets of carcinogens, gene therapy, and they are particularly suited for tissue engineering and tissue reconstitution, our studies can have practical implications on the source of urothelial cells for tissue engineering of various parts of the urinary tract, the cellular origin of in vivo urothelial wound healing following the surgical removal of the bladder, the possible involvement of urothelial cells in interstitial cystitis and in site-specific variations in bacterium: urothelium interactions, and the cellular origin of various urothelial tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESTRAINT INFLAMMATION

STRESS-INDUCED

NEUROGENIC

BLADDER

Principal Investigator & Institution: Theoharides, Theoharis C.; Professor; Pharmacol & Exper Therapeutics; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 30-APR-2007 Summary: (provided by applicant): The urinary bladder is often the site of subacute or chronic inflammation, in the absence of infection, as in interstitial cystitis (IC), a painful bladder disorder occurring mostly in women. Symptoms of urinary frequency and pelvic pain commonly worsen perimenstrually and under stress in IC. Bladder mastocytosis with mast cell activation has been documented in IC. We also showed that acute immobilizationstress in rodents induced bladder mast cell activation, a process that was dependent on the neuropeptides neurotensin (NT) and substance P (SP), as it was absent in rodents treated with capsaicin to deplete sensory nerve fibers of their SP content and was also inhibited by the NT receptor antagonist SR48692. Moreover, pretreatment of bladder with estradiol increased the stimulatory effect of SP, by activating high affinity estrogen receptors that we have identified on bladder mast cells. It was recently shown that bladder inflammation could not occur in mast cell deficient mice infected with the neurotropic pseudorabies virus. Mast cells are located perivascularly close to nerve processes and may secrete many vasoactive, proinflammatory and neurosensitizing molecules in response to allergic triggers, as well as by direct nerve stimulation and by acute immobilization stress. Corticotropin releasing hormone (CRH) is released from the hypothalamus under stress and activates the hypothalamic-pituitary-adrenal (HPA) axis. However, both CRH and its structurally related urocortin (Ucn) are also released in the periphery where they have proinflammatory effects. CRH and Ucn induced rat skin mast cell activation and increased vascular permeability, both of which were inhibited by pretreatment with neutralizing antiserum to CRH or the CRH-receptor (CRH-R) antagonist, antalarmin. CRH or acute stress-induced skin vascular permeability was absent in W/W v mast cell deficient mice, but was present in their +/+ controls indicating it is mast cell dependent. Acute stress also triggered rat bladder mast cell activation that was blocked by a NTreceptor antagonist. The proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosisfactor-alpha (TNF-alpha) were recently shown to be elevated in urine of IC patients. We are hypothesizing that acute stress releases (CRH) and/or (Ucn) in the bladder leading, directly or through SP or NT, to mast cell activation, increased vascular permeability and the expression of proinflammatory molecules. We propose to use normal and genetically deficient female mice to investigate the effect of acute stress and CRH/Ucn on: (1) bladder mast cell and urothelial Nuclear Factor kappa B (NFkappaB)activation, as well as the levels of histamine,lL-6 and TNF-alpha in the urine collected from an indwelling catheter; (2) bladder vascular permeability quantitated by 99Technetium-gluceptate (99Tc) extravasation; (3) Vascular permeability, urine

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mediator release, as well as NF-kappaB activation in W/W v mast cell deficient mice, as well as in CRH knock-out mice and their +/+ controls; (4) mouse bladder mast cell and urothelial NF-KB activation, as well as secretion of histamine, IL-6 or TNF-alpha induced by intravesical administration of CRH/Ucn. These studies will help us understand how acute stress triggers bladder mast cell activation leading to increased vascular permeability and proinflammatory molecule release. Our findings may be relevant to the pathophysiology of IC and may suggest new therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RHO-MODIFYING CYTOTOXIC NECROTIZING FACTOR OF E. COLI Principal Investigator & Institution: O'brien, Alison D.; Professor of Microbiology & Immunol; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 30-APR-2007 Summary: Cytotoxic necrotizing factor type 1 (CNF1) is a member of a family of bacterial toxins that target the Rho family of small GTP-binding proteins in mammalian cells. CNF1 deamidates a single glutamine residue in RhoA, Cdc42, and Rac1 but not in Ras. This deamidation results in the constitutive activation of these GTPases which can trigger actin stress fiber formation, multinucleation, or cell death, depending on the target cell and dose of toxin. CNF1 is frequently produced by Escherichia coli strains that cause urinary tract infections (UTIs), such as cystitis, prostatitis, and pyelonephritis. In support of this epidemiological connection, we recently showed that CNF1 not only induces apoptosis in 5637 human uroepithelial cells but also provides a growth advantage to uropathogenic E. coli (UPEC) in a mouse model of ascending UTI when compared to CNF1-negative isogenic mutants. Additionally, we found that CNF1 enhances the degree of inflammation and resulting tissue damage in bladders of infected mice and in prostates of rats challenged intraurethrally with CNF1-producing UPEC. Finally, we discovered that CNF1- producing UPEC survive better than CNF1negative isogenic mutants in the presence of human polymorphonuclear leukocytes (PMNs). Taken together, these findings have led us to propose the following hypothesis. CNF1 enhances the pathogenicity of UPEC by: i.) promoting uroepithelial cell shedding; ii.) evoking a large influx of PMNs while providing toxin-producing E. coli protection against PMN-mediated killing, and; iii.) facilitating deeper invasion of the bladder or prostate by the infecting strain. The specific aims designed to test this theory are to: 1.) further define the role that CNF1 plays in the pathogenesis of UPEC-mediated cystitis in the mouse and prostatitis in the rat by analyzing the interaction of CNF1 or CNF1expressing UPEC with PMNs from these animals and by defining the CNF1-mediated cytokine response that evokes PMN influx; 2) investigate the cellular and cytokine responses of a human bladder organoid to CNF1 or a CNF1-producing UPEC strain; 3.) identify the functional receptor for CNF1 by sequential biochemical and molecular approaches, and; 4.) continue to evaluate CNF1 structure and function by characterizing the CNF1 epitopes recognized by neutralizing monoclonal antibodies and by analyzing chimeric molecules comprised of portions of CNF1 and the related toxins CNF2, Pasteurella multocida toxin, and the Bordetella dermonecrotic toxin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF NITRIC OXIDE IN INTERSTITIAL CYSTITIS Principal Investigator & Institution: Birder, Lori A.; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 30-JUN-2004 Summary: (Adapted from the Applicant's Abstract): Recent evidence suggests that alterations in afferents or epithelial cells in the urinary bladder can lead to changes in neural excitability and may be part of the etiology of interstitial cystitis (IC). IC is a chronic clinical syndrome of unknown cause and presents with varying and complex sensory symptoms. This may involve a primary defect in afferent neurons or a change in their peripheral environment. Preliminary data indicate that IC in cats can alter the release of chemical mediators (nitric oxide, NO; ATP) from afferent nerves as well as the urothelium. It has been suggested that altered chemical release may influence afferent excitability as well as urothelial membrane function, by increasing the permeability to noxious substances. These data raise the possibility that the urothelium is involved in intercellular signaling in the urinary bladder and neural-epithelial interactions can modulate bladder function. The proposed experiments will use new methods such as cultured urothelial cells and a selective NO porphyrinic microsensor in a naturally occurring animal model of IC (feline interstitial cystitis), which has been demonstrated to have many similarities with IC in humans, to examine the hypothesis that chemical and/or intracellular signaling mechanisms in afferent or epithelial cells in the urinary bladder are altered in IC. Naturally occurring IC rather than acute bladder injury or inflammation models in healthy animals permit more relevant studies of pathophysiology of IC. Aim #1 will evaluation the characteristics of the urothelium in both normal and IC cats. The location of afferent nerves next to the urothelium suggests that urothelial cells might be targets for transmitters released from bladder nerves or that release by epithelial cells could alter the excitability of afferents. Aim #2 will evaluate the characteristics of bladder afferents in both normal and IC cats. We will evaluate the properties of normal bladder afferents to determine how afferents can be altered in IC. These studies may lead to selective pharmacologic interventions aimed at targeting neural-epithelial release or signaling defects and could provide a new prospective on the pathophysiology and clinical management of bladder disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF TNF IN BLADDER INFLAMMATION Principal Investigator & Institution: Klumpp, David J.; Urology; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Interstitial cystitis (IC) is a debilitating, neurogenic bladder disease affecting primarily women with symptoms of pelvic pain, urinary frequency, and urgency. The etiology of IC is unknown, but chronic inflammation is associated with a large subset of patients. Mast cells are thought to play a central role in the bladder inflammation associated with IC, and we have recently shown that mast cells directly induce inflammatory responses in human urothetial cells that are mediated by tumor necrosis factor alpha (TNF). Although little is known about the role of TNF in bladder inflammation, anti-TNF therapy has proven efficacious in the treatment of other chronic inflammatory diseases including Crohn's disease and rheumatoid arthritis. Therefore, our hypothesis is that TNF is a major mediator of bladder inflammation induced by mast cells. To test this hypothesis, we have developed a culture model of mast cell-urothelial cell interactions and a mouse model of neurogenic cystitis using the neurotropic psuedorabies virus (PRV) that does not infect the bladder yet induces a centrally-mediated cystitis that mimics important aspects of IC including voiding dysfunction, involvement of mast ceils, and expression of inflammatory markers. In Aim 1, we will determine the TNF signaling requirements for urothelial inflammatory

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responses to primary murine mast cells in culture using specific antibodies and RNA interference technologies. In Aim 2, the role of mast cells and TNF in neurogenic cystitis will be determined by infusing wild type and TNF knockout mast cells into mast celldeficient mice and then inducing cystitis with PRV. Similar experiments will also be performed with TNF receptor knockout mice. In Aim 3, the impact of chronic TNF exposure on bladder inflammation will be assessed using an existing transgenic mouse that expresses elevated systemic TNF and using mouse lines engineered to specifically express TNF in the urothelium. In Aim 4, the effects of anti-TNF therapy will be tested in both the neurogenic and chronic models of TNF-induced bladder inflammation using a TNF blocking antibody. Thus, this project will determine the role of TNF in bladder inflammation and examine a potential therapy for IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRESS INDUCED NEUROINFLAMMATORY CHANGES IN INTERSTITIAL CYSTITIS PATIENTS Principal Investigator & Institution: Lutgendorf, Susan K.; Associate Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This study is comparing the effect of experimentally induced stress on inflammatory mediators and neuroendocrine responses of patients with interstitial cystitis and healthy controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF NK-KB SIGNALING PATHWAY--INTESTITIAL CYSTITS Principal Investigator & Institution: Rackley, Raymond; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Information transfer from the cellular membrane to the nucleus involves several wall-characterized molecular signaling pathways that lead to transcriptional activation. One of the most important pathways of information transfer is the NF-kappaB (nuclear factor-kappaB) signaling pathway involved in the regulation of an exceptionally large number of genes responsible for a cellular response in an organ system such as the bladder to inflammation, infection, and other stressful cellular situations that requires rapid reprogramming of gene expression. While the exact etiology of Interstitial Cystitis (IC), a debilitating, chronic inflammatory syndrome of the bladder remains elusive, the common translational finding between proposed clinical etiologies is that they are all known to be cellular activators of the intracellular NF-kappaB signaling pathway. We hypothesize that the pathogenesis of the bladder response in IC is due to activation of the NF-kappaB signaling pathway. We will test this hypothesis by characterizing the NF-kappaB signaling pathway and regulated cellular genetic expression in bladder tissue (Specific Aim 1) as well as urothelial cell cultures (Specific Aim 2) from IC patients compared to controls. In addition to establishing NFkappaB signaling as the essential pathway for the bladder response in IC, the specific aims will determine whether the activated signaling represents a dysfunctional (aberrant internal cellular control of the signaling pathway) versus functional (signaling pathway response to external cellular stimulation) urothelial response to extra-cellular stimulation. The significance of determining whether the activation of the NF-kappaB signaling response is functional verses dysfunctional is related to the development of

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novel clinical markers as wall as therapeutic interventions directed at the pathogenesis of IC. Our IC bladder tissue in Specific Aim 1 will be used to corroborate potential diagnostic gene (dysfunctional inhibitor or kinase proteins due to gene mutations) or post-transcription clinical markers that give rise to aberrant NF-kappaB regulation in urothelial cell culture experiments from Specific Aim 2. Future aims for developing treatments based on the pathogenesis of IC from activated NF-kappaB signaling will focus on modulation of the extra-cellular stimulation and downregulation of acute and chronic hyper-activation in the functional response versus development of interventions that address the molecular signaling defects associated with the dysfunctional response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: URINE AND BLADDER MARKERS OF INTERSTITIAL CYSTITIS Principal Investigator & Institution: Erickson, Deborah R.; Associate Professor; Surgery; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Interstitial cystitis (IC) is a multifactorial syndrome, with several proposed etiologies. No clinical or histological factors are pathognomonic, and the diagnosis is essentially one of exclusion. A major problem with current IC research is the lack of objective markers for this symptom complex. The investigators' broad, long-term goals are to identify objective markers of IC, which will be valuable for many purposes. These include: (1) identifying subsets of IC patients with specific etiologies, (2) selecting patients for focused basic research on specific etiologies, (3) selecting patients for treatments directed towards specific etiologies, (4) testing whether the treatments truly are resolving the specific pathophysiologic processes. Since the etiologies of IC are still unknown, the best approach at this time is to seek associations between the proposed marker and other clinical/pathologic features of IC. Several urine components are known to be elevated in IC, and may be useful objective markers. Many of these markers are thought to reflect specific underlying pathophysiologies of IC. The markers include glycosaminoglycans, MUC-1 glycoprotein, hyaluronic acid, methylhistamine, interleukin-6, interleukin-8, cyclic GMP (a reflection of nitric oxide synthase), antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factorlike growth factor, insulin-like growth factor and insulin-like growth factor binding protein 3. This study will test for associations between these urine markers and other features of IC, including an objective measurement of bladder permeability (Aims 1 and 2), symptom response to bladder distention (Aim 3) and relevant objective features of bladder biopsies (Aim 4). The ideal outcome will be to identify markers relevant to specific etiologies, which associate strongly with other markers relevant to the same etiologies. The markers with the strongest associations will be useful for future basic and clinical research directed towards specific etiologies of IC. This focused research will lead to improved, specific treatments for IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYSTITIS

URINE

ANTIPROLIFERATIVE

PEPTIDE

IN

INTERSTITIAL

Principal Investigator & Institution: Keay, Susan F.; Professor of Medicine; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-MAR-2006 Summary: (Adapted from the Applicant's Abstract): Interstitial cystitis (IC) is a chronic bladder disease with often devastating effects on the lives of approximately 450,000

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people in the U.S. The etiology of IC is unknown, and there is currently no reliably effective treatment. It is therefore important to continue to search for a cause of this debilitating disorder in order to systematically devise an effective therapy. The applicants report discovering two, specific and significant abnormalities in the urine of IC patients as compared to controls, which may be linked to the pathogenesis of this disease - the presence of a low molecular weight urine peptide that inhibits the proliferation of bladder epithelial cells in vitro (antiproliferative factor, or APF) and complex changes in the levels of specific urine epithelial cell growth factors, including significantly decreased urine levels of heparin-binding epidermal growth factor-like growth factor. Because a damaged bladder epithelium is a central finding in IC, it is possible that the APF and the growth factor abnormalities are directly involved in the pathogenesis of this disease. The proposed research is designed to determine the mechanisms by which the APF regulates bladder epithelial cell proliferation. In addition, specific effects of HPLC-purified APF on bladder epithelial cell physiology in vitro will be confirmed in vivo using a mouse model. The applicants suggest data from these studies should yield valuable information regarding the regulation of bladder epithelial proliferation and the pathogenesis of IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UROPATHOGENIC E COLI VIRULENCE GENES--COMPREHENSIVE ANALYSIS Principal Investigator & Institution: Donnenberg, Michael S.; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001 Summary: Uropathogenic E. coli (UPEC) are the leading cause of all types of urinary tract infections (UTIs): cystitis and pyelonephritis, community- acquired and nosocomial, complicated and uncomplicated, symptomatic and asymptomatic. Despite many of study, a clear understanding of the pathogenesis of UPEC infections has not emerged. With the exception of type-1 and P fimbriae, heretofore suspected virulence factors have not been confirmed to be essential for UT in animal models. Meanwhile, the discovery the pathogenicity islands in UPEC strains has awakened our appreciation that vast stretches of the genomes of these organisms have yet to be scrutinized. We propose a trifaceted approach to accomplish signature-tagged mutagenesis to identify genetic loci required for colonization in our murine model of ascending UTI. Our success thus far in isolating 12 such mutants portends well for the achievement of this aim. Our second specific aim is to identify fragments of E. coli mutants portends well for the achievement of this aim. Our second specific aim is to identify fragments of E. coli CFT073 genome that are not present in E. coli K-12. Our second specific aim is to identify fragments of E. coli CFT073 genome that are not present in E. coli K-12. We have used a PCR-based genome subtraction approach to clone fragments enriched for such sequences and, using this approach have identified a gene encoding the usher from a previously unknown fimbria. Our third specific aim is to use a green fluorescent protein promoter trap and a fluorescence activated cell sorter to identify promoters from E. coli CFT073 that are expressed specifically in the murine urinary tract. Finally, we will prioritize the loci identified in the first three specific aims and select the most promising for further study in vivo and in vitro to determine the mechanisms by which the products these genes contribute to the pathogenesis of UTI. We believe that this comprehensive analysis of the virulence determinants of UPEC will greatly advance our understanding of the pathogenesis of UTI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UROTHELIAL BARRIER FUNCTION AND INTERSTITIAL CYSTITIS Principal Investigator & Institution: Southgate, Jennifer; Professor and Director; University of York Heslington York, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The aetiology of interstitial cystitis (IC) and other chronic inflammatory uropathies is not understood. We propose to develop a model system in which the urothelium will be studied in isolation from modulatory histioenvironmental factors in order to address whether there is an inherent dysfunction in the urothelium, in at least a subset of painful bladder diseases. Our experimental strategy will be to remove modulatory histio-environmental factors by establishing urothelial cells from IC and control patients in a defined in vitro cell culture system. The model system will permit direct comparison of the phenotypic, functional and immunological characteristics of urothelial cells from IC and normal urothelium. We propose to use this system to test a novel hypothesis, namely that the disease is perpetuated by a failure of the urothelium to provide adequate barrier function against the ingress of urine, leading to tissue damage and consequent inflammation. We will further determine if this can arise due to an inherent defect of the urothelium itself, or due to abnormal responses to inflammatory cytokines produced as a consequence of transient infection or trauma. To these ends, we will study the urothelial cell cultures for their ability to a) Undergo differentiation, b) Form a functional barrier urothelium and c) Show a normal response to archetypal pro- and anti-inflammatory cytokines. The work will be important in establishing whether urothelial cells from patients with IC are inherently abnormal, or whether the aetiopathology of IC is secondary to other factors. The power of this approach lies in its capability of providing evidence of disease subsets and its potential to reveal targets for therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UROTHELIAL DIFFERENTIATION IN INTERSTITIAL CYSTITIS Principal Investigator & Institution: Liebert, Monica; Director; Urology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Interstitial cystitis is a poorly understood syndrome that includes pelvic pain, frequent urination and urinary urgency. There is increasing evidence that mature differentiated urothelial antigens and barrier functions are lost in patients with interstitial cystitis and in a spontaneous cat model of interstitial cystitis. We have developed a unique panel of biomarkers for different stages of urothelial differentiation. In these exploratory studies, we propose to perform the first systematic evaluation of urothelial differentiation in interstitial cystitis through the following Specific Aims: Aim 1: to evaluate the expression of biomarkers in urothelial cells taken from tissues. Normal urothelial cells will be harvested from urothelial tissues (bladder or ureter) and evaluated by flow cytometry, immunostaining, RT-PCR and Northern and Western blotting for expression of a panel of biomarkers. These studies will confirm the utility of the biomarker panel in defining specific stages of urothelial differentiation in situ. Aim 2: to study biomarker expression in urine samples. Urine samples will be collected from interstitial cystitis patients and normal volunteers. Evaluation of urothelial differentiation biomarker content will be performed. Soluble forms of the biomarkers in the urine will be evaluated by qualitative and quantitative immunoassay. Cells recovered from the urine sample will also be tested by immunostaining, immunoassay, and RT-PCR. Results of the biomarker assays will be compared to patient

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characteristics. These exploratory studies will develop a new series of biomarkers that may be informative for the diagnosis, patient stratification and effective use of treatment modalities for interstitial cystitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR PERMEABILITY IN DIABETIC NEPHROPATHY Principal Investigator & Institution: Goligorsky, Michael S.; Professor; Medicine; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The recent description of interstitial fibrosis and renal failure in a streptozotocin model of diabetes in rats subjected to a brief period of renal ischemia provides a good model of human DN and may shed light on the potential pathogenetic mechanisms of this phenomenon. Such new observations, unexplained by the currently prevailing hyperfiltration hypothesis, call for alterative hypoxia-inducible mechanisms of progression in DN. Indeed, it has been demonstrated that hypoxia is itself a potent regulator of gene expression, acting via transcriptional control and mRNA stability to alter the expression of a wide variety of hormones, growth factors, vasoactive compounds and molecules involved in intermediary metabolism. Prominent among hypoxia-inducible growth factors is vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). We hypothesize that the combination of elevated VEGF production, increased post-glomerular vascular permeability and transduction of glycosylated proteins trigger the cascade of events which lead to interstitial fibrosis. Specifically, transudated glycated serum constituents, on the other hand, stimulate fibroblast proliferation, differentiation into myofibroblasts and synthesis of matrix proteins, while on the other hand, these glycosylated products inhibit angiogenesis, thus maintaining the state of chronic hypoxia. This hypothesis will be tested functionally (hemodynamic parameters, tissue oxygenation, expression of angiogenic and angiostatic factors, effects of anti-VEGF and VEGF on these parameters), morphologically (mapping of glycated proteins, proteoglycans, glycoproteins, and other markets of vascular permeability), using approaches of cell biology (isolation of renal fibroblasts, cocultures of endothelial cells with fibroblasts, parameters characterizing cell cycle and their modification by glycated matrix/serum proteins utilized as a substratum, expression of genes and gene products participating in matrix synthesis and degradation and the influence of glycated proteins on these parameters,) cellular physiological approaches (endothelial cell migration and angiogenic potential under the conditions of dysfunctional NO synthase or perturbed repertoire of glycated matrix proteins, balance between the vascular permeability and angiogenesis as affected by glycated proteins and VEGF, and the potential resolution of fibrosis by angiogenic promoters). The proof of this unifying hypothesis of endothelium-dependent fibroblast activation feeding back to inhibit angiogenesis, will require studies on several levels of complexity-from molecular and cellular biology to whole animal physiology-and warrants the combined efforts of three problem-targeted investigative groups. If proven to be correct, this hypothesis could delineate new therapeutic approaches to prevent the progression of diabetic nephropathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRUL FACTORS OF UROPATH ESCHERICHIA COLI Principal Investigator & Institution: Redford, Peter; Medical Microbiol & Immunology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706

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Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Escherichia coli is the most common cause of community-acquired urinary tract infections, resulting in an estimated eight million physician visits a year in the United States. It is also a leading cause of nosocomial infections. Pathogenic E. coli strains carry groupings of genes which are absent in strains that do not cause infection of the urinary tract. These clusters of extra genes have been termed "pathogenicity islands (PAI's)", and the hypothesis to be tested is that they code for the factors necessary in the development of cystitis, pyelonephritis and sepsis. The basis for this hypothesis is the homology of some PAI sequences to virulence genes recognized in other pathogens such as Salmonella, Shigella, Yersinia, Serratia, Vibrio, Bordetella and Streptococcus. Putative virulence genes will be identified on the basis of homologies to sequences of known virulence genes. They also will be found by signature-tagged mutagenesis of a wild-type uropathogenic strain and negative selection of avirulent mutants in a murine model of ascending urinary tract infection. The mouse model will be used to confirm the loss of virulence of signature- tagged mutants as well as test specific allelic knock-outs of candidate virulence genes identified by sequence homologies. New virulence genes will be further examined at the molecular level with analysis of expression conditions and characterization of translation products. The goal of this project is to further the understanding of the mechanisms that underlie the ability of these uropathogenic E. coli to cause disease. The information will promote the development of new chemotherapies and vaccines. The performance of this research plan requires an investigator with a background in basic research. The candidate for this award has worked a year at the NIH and a year so far in the laboratory of the sponsor. The sponsor has more than two decades of research experience in this field and has trained eight Ph.D.'s and six postdoctoral fellows. He heads a fully-equipped and expertly- staffed laboratory at a large university with a distinguished record of research success. The combination of the experience gained in this research, the mentorship given by the sponsor and the educational opportunities offered by the university will accomplish the second goal of this project and meet the ambition of the award candidate: to launch a career as an independent academic investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WOMEN'S HEALTH AND FUNCTIONAL VISCERAL DISORDERS CENTER Principal Investigator & Institution: Mayer, Emeran A.; Microbiology and Immunology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The Women's Health and Functional Visceral Disorders Center is composed of a cohesive group of clinical investigators and basic scientists with strong independent grant-supported research programs in the interactions between the nervous system and the viscera, with special emphasis on stress neurobiology, sex differences and chronic functional disorders. The main focus of the Center is the identification of sex-related factors that play a role in the development, clinical manifestation and treatment response of two common visceral pain syndromes, e.g. Irritable Bowel Syndrome (IBS) and Interstitial Cystitis (IC). Both disorders are common, occur more commonly in females, appear to show sex differences in treatment responses and cause significant morbidity and impairment in quality of life. The Center has two clinical and two basic science Projects, which closely interdigitate and overlap in terms of thematic, experimental approach and hypotheses. Thus, while the clinical

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Projects study sex differences in central stress circuit activation and peripheral outputs of these circuits in human patients with IBS and IC, the two basic Projects study animal models of both disorders. State of the art technology ranging from molecular biological approaches to functional brain imaging techniques will be used to address the following specific aims in the four Projects: 1. Sex Differences in Central Stress Circuit Responsiveness in IBS and IC patients 2. Sex differences in the colonic responses to stress: Role of CRF pathways 3. Sex differences in neuroendocrine and immunologic responses in IBS 4. Sex differences in CRF, noradrenergic function and oxytocin in cats with IC. To facilitate the research, the Center has an Administrative Core and a Scientific Core (Neuroendocrine Measures) and will take advantage of existing NIH-funded core and service facilities on campus, including the CURE: Digestive Diseases Research Center, the UCLA Brain Mapping Center and the GCRC. The Center provides an optimal environment for cooperation and collaboration among its investigators, who already have had a major impact on the field individually. Thus, the synergy expected from the Center promises to have an even larger impact upon expanded research into a highly prevalent, but inadequately treated area of women's health. 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 “cystitis” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for cystitis in the PubMed Central database: •

"Actinobaculum massiliae," a New Species Causing Chronic Urinary Tract Infection. by Greub G, Raoult D.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139656

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Antimicrobial Activity of Intraurethrally Administered Probiotic Lactobacillus casei in a Murine Model of Escherichia coli Urinary Tract Infection. by Asahara T, Nomoto K, Watanuki M, Yokokura T.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90542

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Cefpodoxime-Proxetil versus Trimethoprim-Sulfamethoxazole for Short-Term Therapy of Uncomplicated Acute Cystitis in Women. by Kavatha D, Giamarellou H, Alexiou Z, Vlachogiannis N, Pentea S, Gozadinos T, Poulakou G, Hatzipapas A, Koratzanis G.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149311

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Cluster randomised controlled trial of tailored interventions to improve the management of urinary tract infections in women and sore throat. by Flottorp S, Oxman AD, Havelsrud K, Treweek S, Herrin J.; 2002 Aug 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117890

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Comparison of Escherichia coli Strains Recovered from Human Cystitis and Pyelonephritis Infections in Transurethrally Challenged Mice. by Johnson DE, Lockatell CV, Russell RG, Hebel JR, Island MD, Stapleton A, Stamm WE, Warren JW.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108313

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Development of a Long-Term Ascending Urinary Tract Infection Mouse Model for Antibiotic Treatment Studies. by Hvidberg H, Struve C, Krogfelt KA, Christensen N, Rasmussen SN, Frimodt-Moller N.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89643

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Differences in Virulence Factors among Clinical Isolates of Escherichia coli Causing Cystitis and Pyelonephritis in Women and Prostatitis in Men. by Ruiz J, Simon K, Horcajada JP, Velasco M, Barranco M, Roig G, Moreno-Martinez A, Martinez JA, Jimenez de Anta T, Mensa J, Vila J.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154654

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Establishment of a Persistent Escherichia coli Reservoir during the Acute Phase of a Bladder Infection. by Mulvey MA, Schilling JD, Hultgren SJ.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98534

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Evaluating the benefits of antimicrobial prophylaxis to prevent urinary tract infections in children: a systematic review. by Le Saux N, Pham B, Moher D.; 2000 Sep 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80458

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Genomic Analysis of a Pathogenicity Island in Uropathogenic Escherichia coli CFT073: Distribution of Homologous Sequences among Isolates from Patients with Pyelonephritis, Cystitis, and CatheterAssociated Bacteriuria and from Fecal Samples. by Guyer DM, Kao JS, Mobley HL.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108533

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In Vivo Dynamics of Type 1 Fimbria Regulation in Uropathogenic Escherichia coli during Experimental Urinary Tract Infection. by Gunther NW IV, Lockatell V, Johnson DE, Mobley HL.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98232

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In Vivo Phase Variation of Escherichia coli Type 1 Fimbrial Genes in Women with Urinary Tract Infection. by Lim JK, Gunther NW IV, Zhao H, Johnson DE, Keay SK, Mobley HL.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108346

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Lipopolysaccharide-responder and nonresponder C3H mouse strains are equally susceptible to an induced Escherichia coli urinary tract infection. by Hopkins W, Gendron-Fitzpatrick A, McCarthy DO, Haine JE, Uehling DT.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173927

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Molecular Epidemiologic Approaches to Urinary Tract Infection Gene Discovery in Uropathogenic Escherichia coli. by Zhang L, Foxman B, Manning SD, Tallman P, Marrs CF.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97380

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PCR Detection of Adenovirus in a Bone Marrow Transplant Recipient: Hemorrhagic Cystitis as a Presenting Manifestation of Disseminated Disease. by Echavarria MS, Ray SC, Ambinder R, Dumler JS, Charache P.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84519

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Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. by Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M.; 2001 Jun 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33514

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Randomized, double-blind comparison of single-dose regimens of rufloxacin and pefloxacin for acute uncomplicated cystitis in women. French Multicenter Urinary Tract Infection-Rufloxacin Group. by Jardin A, Cesana M.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162511

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Risk Factors for Antibiotic-Resistant Escherichia coli Isolated from Hospitalized Patients with Urinary Tract Infections: a Prospective Study. by Sotto A, De Boever CM, Fabbro-Peray P, Gouby A, Sirot D, Jourdan J.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87756

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Serum Immunoglobulin Response and Protection from Homologous Challenge by Proteus mirabilis in a Mouse Model of Ascending Urinary Tract Infection. by Johnson DE, Bahrani FK, Lockatell CV, Drachenberg CB, Hebel JR, Belas R, Warren JW, Mobley HL.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97083

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Single-dose rufloxacin versus 3-day norfloxacin treatment of uncomplicated cystitis: clinical evaluation and pharmacodynamic considerations. by Del Rio G, Dalet F, Aguilar L, Caffaratti J, Dal-Re R.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163124

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Time Course and Host Responses to Escherichia coli Urinary Tract Infection in Genetically Distinct Mouse Strains. by Hopkins WJ, Gendron-Fitzpatrick A, Balish E, Uehling DT.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108272

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Treatment of Community-Acquired Acute Uncomplicated Urinary Tract Infection with Sparfloxacin versus Ofloxacin. by Henry D, Ellison W, Sullivan J, Mansfield DL, Magner DJ, Dorr MB, Talbot GH, Group FT.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105806

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Treatment of Mice with Staphylococcal Enterotoxin B Enhances Resolution of an Induced Escherichia coli Urinary Tract Infection and Stimulates Production of Proinflammatory Cytokines. by Morin MD, Hopkins WJ.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108226

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Trends in Antimicrobial Resistance among Urinary Tract Infection Isolates of Escherichia coli from Female Outpatients in the United States. by Karlowsky JA, Kelly LJ, Thornsberry C, Jones ME, Sahm DF.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127340

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

A case of cannabinoid rotation in a young woman with chronic cystitis. Author(s): Krenn H, Daha LK, Oczenski W, Fitzgerald RD. Source: Journal of Pain and Symptom Management. 2003 January; 25(1): 3-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565180&dopt=Abstract

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A case of familial clustering of interstitial cystitis and chronic pelvic pain syndrome. Author(s): Dimitrakov JD. Source: Urology. 2001 August; 58(2): 281. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489726&dopt=Abstract

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A case of lupus peritonitis and cystitis after ovulation induction therapy. Author(s): Tsunoda S, Takano H, Inoue K, Yoshikawa T. Source: American Journal of Obstetrics and Gynecology. 2003 September; 189(3): 888-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526338&dopt=Abstract

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A child with cystitis and lymphadenopathy. Author(s): Listernick R. Source: Pediatric Annals. 2002 July; 31(7): 396-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149794&dopt=Abstract

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A comparison of multiple urine markers for interstitial cystitis. Author(s): Erickson DR, Xie SX, Bhavanandan VP, Wheeler MA, Hurst RE, Demers LM, Kushner L, Keay SK. Source: The Journal of Urology. 2002 June; 167(6): 2461-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992058&dopt=Abstract

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

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A diagnostic in vitro urine assay for interstitial cystitis. Author(s): Keay S, Zhang CO, Hise MK, Hebel JR, Jacobs SC, Gordon D, Whitmore K, Bodison S, Gordon N, Warren JW. Source: Urology. 1998 December; 52(6): 974-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9836539&dopt=Abstract

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A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair. Author(s): Keay S, Warren JW. Source: Medical Hypotheses. 1998 July; 51(1): 79-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9881843&dopt=Abstract

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A laboratory stress model for examining stress and symptomatology in interstitial cystitis patients. Author(s): Lutgendorf SK, Kreder KJ, Rothrock NE, Ratliff TL, Zimmerman B. Source: Urology. 2001 June; 57(6 Suppl 1): 122. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378109&dopt=Abstract

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A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. Author(s): Sant GR, Propert KJ, Hanno PM, Burks D, Culkin D, Diokno AC, Hardy C, Landis JR, Mayer R, Madigan R, Messing EM, Peters K, Theoharides TC, Warren J, Wein AJ, Steers W, Kusek JW, Nyberg LM; Interstitial Cystitis Clinical Trials Group. Source: The Journal of Urology. 2003 September; 170(3): 810-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913705&dopt=Abstract

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A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. The Interstitial Cystitis Data Base Study Group. Author(s): Propert KJ, Schaeffer AJ, Brensinger CM, Kusek JW, Nyberg LM, Landis JR. Source: The Journal of Urology. 2000 May; 163(5): 1434-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751852&dopt=Abstract

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A study to detect Gardnerella vaginalis DNA in interstitial cystitis. Author(s): Agarwal M, Dixon RA. Source: Bju International. 2001 December; 88(9): 868-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851605&dopt=Abstract

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A study to detect Helicobacter pylori in fresh and archival specimens from patients with interstitial cystitis, using amplification methods. Author(s): Agarwal M, Dixon RA. Source: Bju International. 2003 June; 91(9): 814-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780839&dopt=Abstract

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Additional cases of pseudotumoral eosinophilic cystitis. Author(s): Hoeffel JC, Galloy MA. Source: Pediatric Radiology. 2001 February; 31(2): 132-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214684&dopt=Abstract

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Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow transplantation. Author(s): Akiyama H, Kurosu T, Sakashita C, Inoue T, Mori Si, Ohashi K, Tanikawa S, Sakamaki H, Onozawa Y, Chen Q, Zheng H, Kitamura T. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 May 1; 32(9): 1325-30. Epub 2001 April 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303268&dopt=Abstract

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Alkalinized intravesical lidocaine to treat interstitial cystitis: absorption kinetics in normal and interstitial cystitis bladders. Author(s): Henry RA, Patterson L, Nickel C, Morales A. Source: Urology. 2001 June; 57(6 Suppl 1): 119. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378101&dopt=Abstract

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An unusual presentation of emphysematous cystitis. Author(s): Weddle J, Brunton B, Rittenhouse DR. Source: The American Journal of Emergency Medicine. 1998 November; 16(7): 664-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9827742&dopt=Abstract

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Antibiotic treatment for cystitis. Author(s): Leibovici L. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 September; 52(482): 708-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236271&dopt=Abstract

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Antibiotic treatment for five days is effective in children with acute cystitis. Author(s): Abrahamsson K, Hansson S, Larsson P, Jodal U. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(1): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883819&dopt=Abstract

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Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor: sensitive and specific urine markers for interstitial cystitis. Author(s): Keay S, Zhang CO, Marvel R, Chai T. Source: Urology. 2001 June; 57(6 Suppl 1): 104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378066&dopt=Abstract

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Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. Author(s): Sun Y, Keay S, De Deyne PG, Chai TC. Source: The Journal of Urology. 2001 November; 166(5): 1951-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586266&dopt=Abstract

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Basic science research on the urinary bladder and interstitial cystitis: new genetic approaches. Author(s): Liebert M. Source: Urology. 2001 June; 57(6 Suppl 1): 7-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378042&dopt=Abstract

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Benign cystitis in children mimicking rhabdomyosarcoma. Author(s): Rosenberg HK, Eggli KD, Zerin JM, Ortega W, Wallach MT, Kolberg H, Lebowitz RL, Snyder HM. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1994 December; 13(12): 921-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7877202&dopt=Abstract

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Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study. Author(s): Tomaszewski JE, Landis JR, Russack V, Williams TM, Wang LP, Hardy C, Brensinger C, Matthews YL, Abele ST, Kusek JW, Nyberg LM; Interstitial Cystitis Database Study Group. Source: Urology. 2001 June; 57(6 Suppl 1): 67-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378053&dopt=Abstract

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Biosynthetic reactions and ultrastructure of urothelial cells in chronic cystitis and cystopathies. Author(s): Nepomnyashchikh LM, Aidagulova SV, Ivaninskii OI, Kunin IS. Source: Bulletin of Experimental Biology and Medicine. 2002 September; 134(3): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512008&dopt=Abstract

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BK virus (BKV) quantification in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagic cystitis, although wide individual variations exist. Author(s): Priftakis P, Bogdanovic G, Kokhaei P, Mellstedt H, Dalianis T. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 January; 26(1): 71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589836&dopt=Abstract

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BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation. Author(s): Iwamoto S, Azuma E, Hori H, Hirayama M, Kobayashi M, Komada Y, Nishimori H, Miyahara M. Source: Pediatric Hematology and Oncology. 2002 June; 19(4): 255-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051592&dopt=Abstract

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BK virus-associated hemorrhagic cystitis in a Human Immunodeficiency Virusinfected patient. Author(s): Barouch DH, Faquin WC, Chen Y, Koralnik IJ, Robbins GK, Davis BT. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 August 1; 35(3): 326-9. Epub 2002 July 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115100&dopt=Abstract

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Bladder epithelial cells from patients with interstitial cystitis produce an inhibitor of heparin-binding epidermal growth factor-like growth factor production. Author(s): Keay S, Kleinberg M, Zhang CO, Hise MK, Warren JW. Source: The Journal of Urology. 2000 December; 164(6): 2112-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061938&dopt=Abstract

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Bladder hypersensitivity of interstitial cystitis complicated by allergic diseases. Author(s): Yamada T, Murayama T, Mita H, Akiyama K. Source: Urology. 2001 June; 57(6 Suppl 1): 125. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378117&dopt=Abstract

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Bladder mast cell expression of high affinity oestrogen receptors in patients with interstitial cystitis. Author(s): Pang X, Cotreau-Bibbo MM, Sant GR, Theoharides TC. Source: British Journal of Urology. 1995 February; 75(2): 154-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7850318&dopt=Abstract

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Bladder microvasculature and the effects of hydrodistention in interstitial cystitis. Author(s): Rosamilia A, Cann L, Scurry J, Rogers P, Dwyer P. Source: Urology. 2001 June; 57(6 Suppl 1): 132. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378134&dopt=Abstract

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Bladder microvasculature in women with interstitial cystitis. Author(s): Rosamilia A, Cann L, Dwyer P, Scurry J, Rogers P. Source: The Journal of Urology. 1999 June; 161(6): 1865-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332455&dopt=Abstract

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Bladder replacement by ileocystoplasty: the final treatment for interstitial cystitis. Author(s): Christmas TJ, Holmes SA, Hendry WF. Source: British Journal of Urology. 1996 July; 78(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8795403&dopt=Abstract

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Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis. Author(s): Chai TC, Zhang CO, Shoenfelt JL, Johnson HW Jr, Warren JW, Keay S. Source: The Journal of Urology. 2000 May; 163(5): 1440-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751853&dopt=Abstract

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Boon's disease: hemorrhagic cystitis in conjunction with massive exfoliation of degenerated urothelial cells (apoptosis?) during intercontinental flights in an otherwise healthy person. Author(s): Kok LP. Source: Diagnostic Cytopathology. 2001 December; 25(6): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747232&dopt=Abstract

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Botanical perspectives on health: of cystitis and cranberries. Author(s): Patel N, Daniels IR. Source: J R Soc Health. 2000 March; 120(1): 52-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918785&dopt=Abstract

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Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women. Author(s): Kavatha D, Giamarellou H, Alexiou Z, Vlachogiannis N, Pentea S, Gozadinos T, Poulakou G, Hatzipapas A, Koratzanis G. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 897-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604518&dopt=Abstract

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Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment. Author(s): Keay S, Seillier-Moiseiwitsch F, Zhang CO, Chai TC, Zhang J. Source: Physiological Genomics. 2003 July 7; 14(2): 107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847144&dopt=Abstract

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Chemotherapy for leukaemia following previous pelvic radiotherapy is associated with severe enteritis and haemorrhagic cystitis. Author(s): Macheta M, Chopra R, Morgenstern G, Chang J. Source: Annals of Hematology. 2001 August; 80(8): 485-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563597&dopt=Abstract

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Chronic cystitis caused by Corynebacterium urealyticum detected by polymerase chain reaction. Author(s): Simoons-Smit AM, Savelkoul PH, Newling DW, Vandenbroucke-Grauls CM. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2000 December; 19(12): 949-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205634&dopt=Abstract

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Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis. Author(s): Gonzalez-Fraile MI, Canizo C, Caballero D, Hernandez R, Vazquez L, Lopez C, Izarra A, Arroyo JL, de la Loma A, Otero MJ, San Miguel JF. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2001 March; 3(1): 44-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11429040&dopt=Abstract

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Clinical conversations: nurses who work with patients with interstitial cystitis. Author(s): Bates P, Getz B, Gibbs E, Neu L, Pobursky J. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2000 April; 20(2): 109-10, 115-6; Quiz 117-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998121&dopt=Abstract

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Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation. Author(s): Leung AY, Mak R, Lie AK, Yuen KY, Cheng VC, Liang R, Kwong YL. Source: Bone Marrow Transplantation. 2002 March; 29(6): 509-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960271&dopt=Abstract

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Clonal and pathotypic analysis of archetypal Escherichia coli cystitis isolate NU14. Author(s): Johnson JR, Weissman SJ, Stell AL, Trintchina E, Dykhuizen DE, Sokurenko EV. Source: The Journal of Infectious Diseases. 2001 December 15; 184(12): 1556-65. Epub 2001 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740731&dopt=Abstract

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CMV reactivation induced BK virus-associated late onset hemorrhagic cystitis after peripheral blood stem cell transplantation. Author(s): Bielorai B, Shulman LM, Rechavi G, Toren A. Source: Bone Marrow Transplantation. 2001 September; 28(6): 613-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11607776&dopt=Abstract

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Coexistence of vulvar vestibulitis and interstitial cystitis. Author(s): Tarr G, Selo-Ojeme DO, Onwude JL. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2003 October; 82(10): 969. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956850&dopt=Abstract

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Comparative assessment of maximal bladder capacity, 0.9% NaCl versus 0.2 M Kcl, for the diagnosis of interstitial cystitis: a prospective controlled study. Author(s): Daha LK, Riedl CR, Hohlbrugger G, Knoll M, Engelhardt PF, Pfluger H. Source: The Journal of Urology. 2003 September; 170(3): 807-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913704&dopt=Abstract

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Comparison of APF activity and epithelial growth factor levels in urine from Chinese, African-American, and white American patients with interstitial cystitis. Author(s): u Zhang CO, Li ZL, Shoenfelt JL, Kong CZ, Chai TC, Erickson DR, Peters KM, Rovner ES, Keay S. Source: Urology. 2003 May; 61(5): 897-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735999&dopt=Abstract

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Comparison of PCR, enzyme immunoassay and conventional culture for adenovirus detection in bone marrow transplant patients with hemorrhagic cystitis. Author(s): Raboni SM, Siqueira MM, Portes SR, Pasquini R. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 August; 27(3): 270-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878091&dopt=Abstract

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Contracted bladder secondary to eosinophilic cystitis. Author(s): Kayigil O, Ozbagi T, Cakar S, Metin A. Source: International Urology and Nephrology. 2001; 33(2): 341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092651&dopt=Abstract

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Coping strategies in patients with interstitial cystitis: relationships with quality of life and depression. Author(s): Rothrock NE, Lutgendorf SK, Kreder KJ. Source: The Journal of Urology. 2003 January; 169(1): 233-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478143&dopt=Abstract

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Current investigations and treatment of interstitial cystitis. Author(s): Gousse AE, Tiguert R, Madjar S. Source: Curr Urol Rep. 2000 October; 1(3): 190-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084313&dopt=Abstract

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Current management of interstitial cystitis. Author(s): Lukban JC, Whitmore KE, Sant GR. Source: The Urologic Clinics of North America. 2002 August; 29(3): 649-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476528&dopt=Abstract

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Cystitis cystica glandularis masquerading as a bladder tumor. Author(s): Singh I, Ansari MS. Source: International Urology and Nephrology. 2001; 33(4): 635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452616&dopt=Abstract

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Cytologic manifestations of cystitis follicularis in urine specimens. Author(s): Zaharopoulos P. Source: Diagnostic Cytopathology. 2002 October; 27(4): 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357496&dopt=Abstract

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Cytomegalovirus-induced hemorrhagic cystitis in AIDS patient treated successfully with valganciclovir. Author(s): Studemeister A. Source: Aids (London, England). 2002 July 5; 16(10): 1437-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131229&dopt=Abstract

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Daily stress and symptom exacerbation in interstitial cystitis patients. Author(s): Rothrock NE, Lutgendorf SK, Kreder KJ, Ratliff TL, Zimmerman B. Source: Urology. 2001 June; 57(6 Suppl 1): 122. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378108&dopt=Abstract

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Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis. Author(s): Keay S, Zhang CO, Shoenfelt JL, Chai TC. Source: Urology. 2003 June; 61(6): 1278-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809929&dopt=Abstract

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Decreased levels of S-100 protein in non-ulcer interstitial cystitis. Author(s): Peeker R, Aldenborg F, Haglid K, Johansson SL, Rosengren L, Fall M. Source: Scandinavian Journal of Urology and Nephrology. 1998 December; 32(6): 395-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9925003&dopt=Abstract

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Demographic, clinical, and treatment parameters influencing the outcome of acute cystitis. Author(s): Echols RM, Tosiello RL, Haverstock DC, Tice AD. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 July; 29(1): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10433573&dopt=Abstract

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Depressive symptoms and quality of life in patients with interstitial cystitis. Author(s): Rothrock NE, Lutgendorf SK, Hoffman A, Kreder KJ. Source: The Journal of Urology. 2002 April; 167(4): 1763-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912405&dopt=Abstract

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Detection of eubacteria in interstitial cystitis by 16S rDNA amplification. Author(s): Heritz DM, Lacroix JM, Batra SD, Jarvi KA, Beheshti B, Mittelman MW. Source: The Journal of Urology. 1997 December; 158(6): 2291-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366378&dopt=Abstract

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Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis. Author(s): Christmas TJ, Smith GL, Rode J. Source: British Journal of Urology. 1996 December; 78(6): 862-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014709&dopt=Abstract

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Diagnosing interstitial cystitis in women with chronic pelvic pain. Author(s): Clemons JL, Arya LA, Myers DL. Source: Obstetrics and Gynecology. 2002 August; 100(2): 337-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151160&dopt=Abstract

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Diagnosis and management of eosinophilic cystitis: a pooled analysis of 135 cases. Author(s): van den Ouden D. Source: European Urology. 2000 April; 37(4): 386-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10765067&dopt=Abstract

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Diagnosis, treatment, and lifestyle changes of interstitial cystitis. Author(s): Henderson LJ. Source: Aorn Journal. 2000 March; 71(3): 525-30, 533-6, 538. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10736638&dopt=Abstract

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Diagnostic dilemma. Emphysematous cystitis. Author(s): Tsao JW, Jun SL. Source: The American Journal of Medicine. 2001 February 15; 110(3): 220, 239. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221634&dopt=Abstract

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Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men. Author(s): Ruiz J, Simon K, Horcajada JP, Velasco M, Barranco M, Roig G, MorenoMartinez A, Martinez JA, Jimenez de Anta T, Mensa J, Vila J. Source: Journal of Clinical Microbiology. 2002 December; 40(12): 4445-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454134&dopt=Abstract

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Discrimination between the ulcerous and the nonulcerous forms of interstitial cystitis by noninvasive findings. Author(s): Koziol JA, Adams HP, Frutos A. Source: The Journal of Urology. 1996 January; 155(1): 87-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7490906&dopt=Abstract

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Diurnal cortisol variations and symptoms in patients with interstitial cystitis. Author(s): Lutgendorf SK, Kreder KJ, Rothrock NE, Hoffman A, Kirschbaum C, Sternberg EM, Zimmerman MB, Ratliff TL. Source: The Journal of Urology. 2002 March; 167(3): 1338-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832727&dopt=Abstract

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Do infectious agents cause interstitial cystitis? Author(s): Duncan JL, Schaeffer AJ. Source: Urology. 1997 May; 49(5A Suppl): 48-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146001&dopt=Abstract

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Does parenteral oestrogen therapy flare up disease activity in patients with systemic lupus erythematosus complicated by haemorrhagic cystitis? Author(s): Yang LY, Huang WJ, Chen WP, Fu LW, Lin CY. Source: Rheumatology (Oxford, England). 1999 April; 38(4): 372-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10378718&dopt=Abstract

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Does the potassium stimulation test predict cystometric, cystoscopic outcome in interstitial cystitis? Author(s): Gregoire M, Liandier F, Naud A, Lacombe L, Fradet Y. Source: The Journal of Urology. 2002 August; 168(2): 556-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131308&dopt=Abstract

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Drug induced cystitis: the need for vigilance. Author(s): Jeremy JY, Mikhailidis DP. Source: British Journal of Urology. 1997 September; 80(3): 511-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9313688&dopt=Abstract

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Drug resistant Mycobacterium bovis cystitis following intravesical bacillus CalmetteGuerin treatment. Author(s): Eichel L, Erturk E, Disant'Agnese A. Source: The Journal of Urology. 1999 December; 162(6): 2096. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569583&dopt=Abstract

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Drug-induced cystitis: the need for vigilance. Author(s): Bramble FJ, Morley R. Source: British Journal of Urology. 1997 January; 79(1): 3-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9043486&dopt=Abstract

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Effect of diagnostic hydrodistension and four intravesical hyaluronic acid instillations on bladder ICAM-1 intensity and association of ICAM-1 intensity with clinical response in patients with interstitial cystitis. Author(s): Leppilahti M, Hellstrom P, Tammela TL. Source: Urology. 2002 July; 60(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100920&dopt=Abstract

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Effect of physiologic levels of urinary potassium on interstitial cystitis symptoms. Author(s): Payne CK, Sirinian E, Azevedo K. Source: Urology. 2001 June; 57(6 Suppl 1): 124. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378114&dopt=Abstract

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Effects of dimethyl sulphoxide and heparin on stretch-activated ATP release by bladder urothelial cells from patients with interstitial cystitis. Author(s): Sun Y, Chai TC. Source: Bju International. 2002 September; 90(4): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175393&dopt=Abstract

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Effects of L-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis. Author(s): Ehren I, Lundberg JO, Adolfsson J, Wiklund NP. Source: Urology. 1998 December; 52(6): 1026-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9836549&dopt=Abstract

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Efficacy of oral doxepin and piroxicam treatment for interstitial cystitis. Author(s): Wammack R, Remzi M, Seitz C, Djavan B, Marberger M. Source: European Urology. 2002 June; 41(6): 596-600; Discussion 601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074775&dopt=Abstract

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Emphysematous cystitis in a patient presenting with paradoxical arterial embolism and intestinal mycobacteriosis without evidence of diabetes. Author(s): Dinkel HP, Lourens S, Brehmer U, Pfammatter R, Triller J, Vock P. Source: European Radiology. 2001; 11(2): 246-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218022&dopt=Abstract

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Emphysematous cystitis, a rare complication of urinary tract infection in a male diabetic patient: a case report. Author(s): Hsin SC, Hsieh MC, Lin HY, Hsia PJ, Shin SJ. Source: Kaohsiung J Med Sci. 2003 March; 19(3): 132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751874&dopt=Abstract

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Emphysematous cystitis. Author(s): Ma JF, McClenathan JH. Source: Journal of the American College of Surgeons. 2001 November; 193(5): 574. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708516&dopt=Abstract

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Emphysematous cystitis: a radiographic diagnosis. Author(s): O'Connor LA, De Guzman J. Source: The American Journal of Emergency Medicine. 2001 May; 19(3): 211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11326348&dopt=Abstract

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Emphysematous cystitis: possible side-effect of cyclophosphamide therapy. Author(s): Abuzarad H, Gadallah MF, Rabb H, Vermess M, Ramirez G. Source: Clinical Nephrology. 1998 December; 50(6): 394-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9877119&dopt=Abstract

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Empirical treatment of acute cystitis in women. Author(s): Nicolle LE. Source: International Journal of Antimicrobial Agents. 2003 July; 22(1): 1-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842322&dopt=Abstract

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Empirical treatment of uncomplicated cystitis. Author(s): Baerheim A. Source: Bmj (Clinical Research Ed.). 2001 November 24; 323(7323): 1197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719397&dopt=Abstract

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Encrusted cystitis with ammonium acid urate calculi: a case report. Author(s): Ito M, Kanno T, Kawase N, Taki Y. Source: Hinyokika Kiyo. 2002 April; 48(4): 221-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048934&dopt=Abstract

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Eosinophilic cystitis in a 4-year-old boy: successful long-term treatment with cyclosporin A. Author(s): Pomeranz A, Eliakim A, Uziel Y, Gottesman G, Rathaus V, Zehavi T, Wolach B. Source: Pediatrics. 2001 December; 108(6): E113. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731640&dopt=Abstract

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Eosinophilic cystitis in adults. Author(s): Itano NM, Malek RS. Source: The Journal of Urology. 2001 March; 165(3): 805-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176473&dopt=Abstract

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Eosinophilic cystitis masquerading as invasive bladder cancer. Author(s): Sekine H, Kojima S, Ohya K. Source: Urologia Internationalis. 1998; 61(2): 128-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9873257&dopt=Abstract

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Eosinophilic cystitis presenting as a recurrent symptomatic bladder mass following intravesical mitomycin C therapy. Author(s): Clark T, Chang SS, Cookson MS. Source: The Journal of Urology. 2002 April; 167(4): 1795. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912421&dopt=Abstract

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Eosinophilic cystitis. Author(s): Verhagen PC, Nikkels PG, de Jong TP. Source: Archives of Disease in Childhood. 2001 April; 84(4): 344-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259238&dopt=Abstract

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Eosinophilic cystitis: eight cases report and literature review. Author(s): Lin HY, Chou YH, Wu WJ, Huang CH, Chai CY. Source: Kaohsiung J Med Sci. 2002 January; 18(1): 30-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017980&dopt=Abstract

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Evaluation of transvaginal theile massage as a therapeutic intervention for women with interstitial cystitis. Author(s): Holzberg A, Kellog-Spadt S, Lukban J, Whitmore K. Source: Urology. 2001 June; 57(6 Suppl 1): 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378103&dopt=Abstract

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Facilitating a conceptual shift: psychological consequences of interstitial cystitis. Author(s): Falvey HM. Source: Bju International. 2001 December; 88(9): 863-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851604&dopt=Abstract

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Factor XIII replacement in stem-cell transplant recipients with severe hemorrhagic cystitis: a report of four cases. Author(s): Demesmay K, Tissot E, Bulabois CE, Bertrand MA, Racadot E, WoronoffLemsi MC, Cahn JY, Deconinck E. Source: Transplantation. 2002 October 27; 74(8): 1190-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438970&dopt=Abstract

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Filarial cystitis with ureteral obstruction. Author(s): Devasia A, Ponnaiya J, Gopalakrishnan G. Source: The Journal of Urology. 1998 May; 159(5): 1637-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554371&dopt=Abstract

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Fishbein/interstitial cystitis association (ICA) survey of interstitial cystitis among family members of ICA members: preliminary analysis. Author(s): Warren J, Jackson T, Meyers D, Xu J. Source: Urology. 2001 June; 57(6 Suppl 1): 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378121&dopt=Abstract

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Florid cystitis glandularis of intestinal type with mucin extravasation: a mimic of adenocarcinoma. Author(s): Young RH, Bostwick DG. Source: The American Journal of Surgical Pathology. 1996 December; 20(12): 1462-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8944039&dopt=Abstract

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Fluorescein angiography of the bladder: technique and relevance to bladder cancer and interstitial cystitis patients. Author(s): Zimmern PE, Laub D, Leach GE. Source: The Journal of Urology. 1995 July; 154(1): 62-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7539868&dopt=Abstract

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Fluoroquinolone use for acute cystitis in an IPA-model managed care organization. Author(s): Aforismo JF, Kaul AF, Tomondy PA, Parry GE, Staubach LB, Regalli G, Dine AP. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1995 December 1; 52(23): 2702-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8601266&dopt=Abstract

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Focal emphysematous cystitis arising in a diverticulum: a case report. Author(s): Wu TT, Huang JS, Huang JK, Lee YH. Source: The Journal of Urology. 1996 February; 155(2): 643. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8558684&dopt=Abstract

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Follicular cystitis--a case report. Author(s): Mandal AK. Source: Indian J Pathol Microbiol. 1999 October; 42(4): 503-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127389&dopt=Abstract

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Formalin treatment of refractory hemorrhagic cystitis in systemic lupus erythematosus. Author(s): Fu LW, Chen WP, Wang HH, Lin AT, Lin CY. Source: Pediatric Nephrology (Berlin, Germany). 1998 November; 12(9): 788-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9874330&dopt=Abstract

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Fosfomycin trometamol and the single-dose treatment of cystitis. Author(s): Greenwood D. Source: Journal of Medical Microbiology. 1994 November; 41(5): 293-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7966199&dopt=Abstract

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Fosfomycin tromethamine: single-dose treatment of acute cystitis. Author(s): Stein GE. Source: Int J Fertil Womens Med. 1999 March-April; 44(2): 104-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10338268&dopt=Abstract

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Gangrenous cystitis in the elderly: pathogenesis and management options. Author(s): White MD, Das AK, Kaufman RP Jr. Source: British Journal of Urology. 1998 August; 82(2): 297-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9722774&dopt=Abstract

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Gangrenous cystitis, not such a rare pathology. Author(s): Gutierrez Minguez E, Arroyo Munoz JL, Espiga Santamaria FJ, Claver Criado M. Source: Presse Med. 1996 October 12; 25(30): 1390. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8958864&dopt=Abstract

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Gangrenous cystitis: a rare cause of colovesical fistula. Author(s): Raza A, Balsitis M, Hosie KB. Source: Postgraduate Medical Journal. 1999 January; 75(879): 34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10396585&dopt=Abstract

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Gastric neobladder for treatment of tuberculosis cystitis. Author(s): Shamsa A. Source: The Journal of Urology. 1998 January; 159(1): 202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9400475&dopt=Abstract

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Genetic evidence supporting the fecal-perineal-urethral hypothesis in cystitis caused by Escherichia coli. Author(s): Yamamoto S, Tsukamoto T, Terai A, Kurazono H, Takeda Y, Yoshida O. Source: The Journal of Urology. 1997 March; 157(3): 1127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9072556&dopt=Abstract

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Genomic analysis of a pathogenicity island in uropathogenic Escherichia coli CFT073: distribution of homologous sequences among isolates from patients with pyelonephritis, cystitis, and Catheter-associated bacteriuria and from fecal samples. Author(s): Guyer DM, Kao JS, Mobley HL. Source: Infection and Immunity. 1998 September; 66(9): 4411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9712795&dopt=Abstract

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Giant botryoid fibroepithelial polyp of bladder with myofibroblastic stroma and cystitis cystica et glandularis. Author(s): Al-Ahmadie H, Gomez AM, Trane N, Bove KE. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2003 March-April; 6(2): 179-81. Epub 2003 February 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574920&dopt=Abstract

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Glutaraldehyde cross-linked collagen occlusion of the ureteral orifices with percutaneous nephrostomy: a minimally invasive option for treatment refractory hemorrhagic cystitis. Author(s): Gonzalez CM, Case JR, Nadler RB. Source: The Journal of Urology. 2001 September; 166(3): 977-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490259&dopt=Abstract

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Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome. Author(s): Russell AL. Source: Medical Hypotheses. 1999 April; 52(4): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465666&dopt=Abstract

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Glycosaminoglycans excretion in interstitial cystitis. Author(s): Akcay T, Konukoglu D. Source: International Urology and Nephrology. 1999; 31(4): 431-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10668936&dopt=Abstract

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Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Author(s): Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 October; 29(4): 745-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589881&dopt=Abstract

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Gynecologic manifestations of interstitial cystitis. Author(s): Myers DL, Aguilar VC. Source: Clinical Obstetrics and Gynecology. 2002 March; 45(1): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862075&dopt=Abstract

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Gynecologic presentation of interstitial cystitis as detected by intravesical potassium sensitivity. Author(s): Parsons CL, Bullen M, Kahn BS, Stanford EJ, Willems JJ. Source: Obstetrics and Gynecology. 2001 July; 98(1): 127-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430970&dopt=Abstract

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Haemorrhagic cystitis and renal dysfunction associated with high dose benzylpenicillin. Author(s): Adlam D, Firoozan S, Gribbin B, Banning AP. Source: The Journal of Infection. 2000 January; 40(1): 102-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10762126&dopt=Abstract

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Haemorrhagic cystitis associated with adenovirus in a patient with AIDS treated for a non-Hodgkin's lymphoma. Author(s): Ghez D, Oksenhendler E, Scieux C, Lassoued K. Source: American Journal of Hematology. 2000 January; 63(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10602165&dopt=Abstract

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Haemorrhagic cystitis: incidence and risk factors in a transplant population using hyperhydration. Author(s): Trotman J, Nivison-Smith I, Dodds A. Source: Bone Marrow Transplantation. 1999 April; 23(8): 797-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10231142&dopt=Abstract

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Hemorrhagic cystitis as a complication of bone marrow transplantation. Author(s): Ilhan O, Koc H, Akan H, Gurman G, Arslan O, Ozcan M, Arikan N, Sencer H, Konuk N, Uysal A, Beksac M. Source: Journal of Chemotherapy (Florence, Italy). 1997 February; 9(1): 56-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9106019&dopt=Abstract

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Hemorrhagic cystitis as an unexpected adverse reaction to temozolomide: case report. Author(s): Islam R, Isaacson BJ, Zickerman PM, Ratanawong C, Tipping SJ. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 October; 25(5): 513-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393995&dopt=Abstract

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Hemorrhagic cystitis due to intravesical instillation of gentian violet completely recovered with conservative therapy. Author(s): Kim SJ, Koh DH, Park JS, Ahn HS, Choi JB, Kim YS. Source: Yonsei Medical Journal. 2003 February; 44(1): 163-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619193&dopt=Abstract

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Hemorrhagic cystitis, chemotherapy, and bladder toxicity. Author(s): Ratliff TR, Williams RD. Source: The Journal of Urology. 1998 March; 159(3): 1044. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9474228&dopt=Abstract

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Hemorrhagic pyelitis, ureteritis, and cystitis secondary to cyclophosphamide: case report and review of the literature. Author(s): Wong TM, Yeo W, Chan LW, Mok TS. Source: Gynecologic Oncology. 2000 February; 76(2): 223-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10637075&dopt=Abstract

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High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine. Author(s): Childs R, Sanchez C, Engler H, Preuss J, Rosenfeld S, Dunbar C, van Rhee F, Plante M, Phang S, Barrett AJ. Source: Bone Marrow Transplantation. 1998 November; 22(9): 889-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9827817&dopt=Abstract

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How do patients with interstitial cystitis present? Author(s): Driscoll A, Teichman JM. Source: The Journal of Urology. 2001 December; 166(6): 2118-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696718&dopt=Abstract

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How does cystitis affect a comparative risk profile of tiaprofenic acid with other nonsteroidal antiinflammatory drugs? An international study based on spontaneous reports and drug usage data. ADR Signals Analysis Project (ASAP) Team. Author(s): Lindquist M, Pettersson M, Edwards IR, Sanderson JH, Taylor NF, Fletcher AP, Schou JS, Savage R. Source: Pharmacology & Toxicology. 1997 May; 80(5): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9181599&dopt=Abstract

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Human herpesvirus-6 as a possible cause of encephalitis and hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Author(s): Kim YJ, Kim DW, Lee DG, Park ST, Park YH, Min CK, Lee S, Choi JH, Lee JW, Min WS, Shin WS, Kim CC. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 May; 16(5): 958-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986964&dopt=Abstract

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Human polyomavirus BK (BKV) load and haemorrhagic cystitis in bone marrow transplantation patients. Author(s): Azzi A, Cesaro S, Laszlo D, Zakrzewska K, Ciappi S, De Santis R, Fanci R, Pesavento G, Calore E, Bosi A. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 1999 October; 14(2): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10588450&dopt=Abstract

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Hydroxyzine therapy for interstitial cystitis. Author(s): Theoharides TC, Sant GR. Source: Urology. 1997 May; 49(5A Suppl): 108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146011&dopt=Abstract

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Hyperbaric oxygen for cyclophosphamide-induced cystitis. Author(s): Hughes MJ, Davis FM, Mark SD, Spearing RL. Source: British Journal of Haematology. 2002 November; 119(2): 575. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406105&dopt=Abstract

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Hyperbaric oxygen for the treatment of radiation cystitis and proctitis. Author(s): Ennis RD. Source: Curr Urol Rep. 2002 June; 3(3): 229-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084193&dopt=Abstract

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Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis. Author(s): Hughes AJ, Schwarer AP, Millar IL. Source: Bone Marrow Transplantation. 1998 September; 22(6): 585-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9758348&dopt=Abstract

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Hyperbaric oxygen therapy for pediatric hemorrhagic cystitis. Author(s): Furness PD 3rd, Palmer LS, Palmer JS, Capelli-Schellpfeffer M, Cheng EY. Source: The Journal of Urology. 1999 May; 161(5): 1596-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210424&dopt=Abstract

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Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis. Author(s): Mathews R, Rajan N, Josefson L, Camporesi E, Makhuli Z. Source: The Journal of Urology. 1999 February; 161(2): 435-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9915420&dopt=Abstract

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Hyperbaric oxygen therapy for Wegener's granulomatosis with cyclophosphamideinduced hemorrhagic cystitis. Author(s): Kuroda I, Kuwata Y, Kakehi Y. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2002 August; 9(8): 470-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225346&dopt=Abstract

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Idiopathic retroperitoneal fibrosis mimicking a pelvic tumor: a case of pericystitis plastica. Author(s): Verit A, Yeni E, Unal D, Kafali H, Ozturk A, Ozardali I. Source: Yonsei Medical Journal. 2003 June 30; 44(3): 548-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833598&dopt=Abstract

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Images in clinical medicine. Emphysematous cystitis. Author(s): Asada S, Kawasaki T. Source: The New England Journal of Medicine. 2003 July 17; 349(3): 258. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867609&dopt=Abstract

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Incidence of physician-diagnosed interstitial cystitis in Olmsted County: a community-based study. Author(s): Roberts RO, Bergstralh EJ, Bass SE, Lightner DJ, Lieber MM, Jacobsen SJ. Source: Bju International. 2003 February; 91(3): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581000&dopt=Abstract

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Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Author(s): Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Waxell T, Koziol JA. Source: Urology. 2002 October; 60(4): 573-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385909&dopt=Abstract

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Intercurrent autoimmune conditions in classic and non-ulcer interstitial cystitis. Author(s): Peeker R, Atanasiu L, Logadottir Y. Source: Scandinavian Journal of Urology and Nephrology. 2003; 37(1): 60-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745747&dopt=Abstract

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Interstitial cystitis coexisting with vulvar vestibulitis in a 4-year-old girl. Author(s): Selo-Ojeme DO, Paranjothy S, Onwude JL. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 2002; 13(4): 261-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189432&dopt=Abstract

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Interstitial cystitis is a legitimate and serious condition. Author(s): Ratner V. Source: American Family Physician. 2002 May 1; 65(9): 1741; Author Reply 1741-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018798&dopt=Abstract

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Interstitial cystitis, pelvic pain, and the relationship to myofascial pain and dysfunction: a report on four patients. Author(s): Doggweiler-Wiygul R, Wiygul JP. Source: World Journal of Urology. 2002 November; 20(5): 310-4. Epub 2002 October 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522588&dopt=Abstract

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Interstitial cystitis. Author(s): Newsome G. Source: Journal of the American Academy of Nurse Practitioners. 2003 February; 15(2): 64-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640941&dopt=Abstract

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Interstitial cystitis: a review of current concepts of aetiology, diagnosis and therapy. Author(s): Ajibona OO, Kehinde EO. Source: Scandinavian Journal of Urology and Nephrology. 2003; 37(3): 253-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775286&dopt=Abstract

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Interstitial cystitis: an update. Author(s): Oberpenning F, van Ophoven A, Hertle L. Source: Current Opinion in Urology. 2002 July; 12(4): 321-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072654&dopt=Abstract

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Interstitial cystitis: diagnosis and treatment options. Author(s): MaLossi J, Chai TC. Source: Curr Womens Health Rep. 2002 August; 2(4): 298-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150758&dopt=Abstract

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Interstitial cystitis--a time for revision of name and diagnostic criteria in the new millennium? Author(s): Quinn MJ. Source: Bju International. 2002 May; 89(7): 795. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966658&dopt=Abstract

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Interstitial cystitis--a time for revision of name and diagnostic criteria in the new millennium? Author(s): Irwin PP. Source: Bju International. 2002 May; 89(7): 794-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966656&dopt=Abstract

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Interstitial cystitis--an elusive clinical target? Author(s): Nickel JC. Source: The Journal of Urology. 2003 September; 170(3): 816-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913706&dopt=Abstract

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Interstitial cystitis-like urinary symptoms among patients with Sjogren's syndrome: a population-based study in Finland. Author(s): Leppilahti M, Tammela TL, Huhtala H, Kiilholma P, Leppilahti K, Auvinen A. Source: The American Journal of Medicine. 2003 July; 115(1): 62-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867237&dopt=Abstract

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Intravesical treatment of severe bacillus Calmette-Guerin cystitis. Author(s): Palou J, Rodriguez-Villamil L, Andreu-Crespo A, Salvador-Bayarri J, VicenteRodriguez J. Source: International Urology and Nephrology. 2001; 33(3): 485-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230277&dopt=Abstract

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Intravesicle formalin instillation with a modified technique for controlling haemorrhage secondary to radiation cystitis. Author(s): Lojanapiwat B, Sripralakrit S, Soonthornphan S, Wudhikarn S. Source: Asian J Surg. 2002 July; 25(3): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376221&dopt=Abstract

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Is interstitial cystitis an infectious disease? Author(s): Keay SK, Warren JW. Source: International Journal of Antimicrobial Agents. 2002 June; 19(6): 480-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135837&dopt=Abstract

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Is TMP-SMX the best first choice for uncomplicated cystitis in women? Author(s): Hegmann T. Source: Jaapa. 2002 September; 15(9): 60-2, 64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395671&dopt=Abstract

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Joseph Parrish, tic doloureux of the bladder and interstitial cystitis. Author(s): Teichman JM, Thompson IM, Taichman NS. Source: The Journal of Urology. 2000 November; 164(5): 1473-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11025685&dopt=Abstract

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Late effects of postradiation cystitis noted on renal dynamic study. Author(s): Erbay N, Spencer RP. Source: Clinical Nuclear Medicine. 1998 January; 23(1): 34-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9442964&dopt=Abstract

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Late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation in children. Author(s): Kondo M, Kojima S, Kato K, Matsuyama T. Source: Bone Marrow Transplantation. 1998 November; 22(10): 995-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849697&dopt=Abstract

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Late-onset hemorrhagic cystitis following bone marrow transplantation: a case report. Author(s): Goddard AG, Saha V. Source: Pediatric Hematology and Oncology. 1997 May-June; 14(3): 273-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185212&dopt=Abstract

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Leukocyte populations in interstitial cystitis and idiopathic reduced bladder storage. Author(s): Al-Hadithi H, Tincello DG, Vince GS, Richmond DH. Source: Urology. 2002 June; 59(6): 851-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031367&dopt=Abstract

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Lipofuscinosis of the urinary bladder: a complication of chronic interstitial cystitis. Author(s): Tzankov A, Peschel R, Stenzl A, Mikuz G. Source: Virchows Archiv : an International Journal of Pathology. 2002 August; 441(2): 200-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418480&dopt=Abstract

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Logical and systematic approach to the evaluation and management of patients suspected of having interstitial cystitis. Author(s): Pontari MA, Hanno PM, Wein AJ. Source: Urology. 1997 May; 49(5A Suppl): 114-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146013&dopt=Abstract

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Long-term experience with pentosanpolysulfate in interstitial cystitis. Author(s): Jepsen JV, Sall M, Rhodes PR, Schmidt D, Messing E, Bruskewitz RC. Source: Urology. 1998 March; 51(3): 381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9510339&dopt=Abstract

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Long-term results of trigone-preserving orthotopic substitution enterocystoplasty for interstitial cystitis. Author(s): van Ophoven A, Oberpenning F, Hertle L. Source: The Journal of Urology. 2002 February; 167(2 Pt 1): 603-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792927&dopt=Abstract

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Long-term use of pentosan polysulfate for interstitial cystitis. Author(s): Evans RJ. Source: Urology. 1999 April; 53(4): 863. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10197877&dopt=Abstract

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Lumbar sympathetic block for pain relief in two patients with interstitial cystitis. Author(s): Doi K, Saito Y, Nikai T, Morimoto N, Nakatani T, Sakura S. Source: Regional Anesthesia and Pain Medicine. 2001 May-June; 26(3): 271-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359229&dopt=Abstract

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Lupus cystitis improved with oral prednisolone therapy. Author(s): Goupille P, Jeannou J, Valat JP. Source: The Journal of Rheumatology. 1996 September; 23(9): 1667. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8877946&dopt=Abstract

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Lupus cystitis in the Japanese. Author(s): Koike T, Takabayashi K. Source: Intern Med. 1996 February; 35(2): 87-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8680110&dopt=Abstract

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Lupus cystitis on Ga-67 scans. Author(s): Lin WY, Lan JL, Wang SJ. Source: Clinical Nuclear Medicine. 2000 September; 25(9): 737. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983772&dopt=Abstract

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Lupus cystitis: a possible additive risk factor for emphysematous cystitis in diabetes mellitus: discussion about one case. Author(s): Granel B, Serratrice J, Juhan V, Rey J, Lechevalier E, Disdier P, Weiller PJ. Source: Lupus. 2000; 9(1): 72-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10713651&dopt=Abstract

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Management of ischemic hemorrhagic cystitis with hyperbaric oxygen therapy. Author(s): Lopez AE, Rodriguez S, Flores I. Source: Undersea & Hyperbaric Medicine : Journal of the Undersea and Hyperbaric Medical Society, Inc. 2001 Spring; 28(1): 35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732883&dopt=Abstract

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Management of lower urinary tract infections and cystitis. Author(s): Anderson RU. Source: The Urologic Clinics of North America. 1999 November; 26(4): 729-35, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584614&dopt=Abstract

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Managing postmenopausal cystitis. Author(s): Hextall A, Cardozo L. Source: Hosp Pract (Off Ed). 1997 June 15; 32(6): 191-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9194809&dopt=Abstract

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Massive extracellular tryptase from activated bladder mast cells in interstitial cystitis. Author(s): Theoharides TC, Kempuraj D, Sant GR. Source: Urology. 2001 October; 58(4): 605-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597550&dopt=Abstract

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Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis. Author(s): Pang X, Boucher W, Triadafilopoulos G, Sant GR, Theoharides TC. Source: Urology. 1996 March; 47(3): 436-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8633418&dopt=Abstract

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Mast cell counts are not useful in the diagnosis of nonulcerative interstitial cystitis. Author(s): Dundore PA, Schwartz AM, Semerjian H. Source: The Journal of Urology. 1996 March; 155(3): 885-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8583599&dopt=Abstract

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Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Author(s): Theoharides TC, Kempuraj D, Sant GR. Source: Urology. 2001 June; 57(6 Suppl 1): 47-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378050&dopt=Abstract

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Mast cells and nerve fibers in interstitial cystitis (IC): an algorithm for histologic diagnosis via quantitative image analysis and morphometry (QIAM). Author(s): Hofmeister MA, He F, Ratliff TL, Mahoney T, Becich MJ. Source: Urology. 1997 May; 49(5A Suppl): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146000&dopt=Abstract

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Mechanism of action and impact of a cystitis clinical practice guideline on outcomes and costs of care in an HMO. Author(s): O'Connor PJ, Solberg LI, Christianson J, Amundson G, Mosser G. Source: Jt Comm J Qual Improv. 1996 October; 22(10): 673-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8923167&dopt=Abstract

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Medical therapy in interstitial cystitis: the essex experience. Author(s): Lewi H. Source: Urology. 2001 June; 57(6 Suppl 1): 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378104&dopt=Abstract

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Microsatellite alterations in urinary sediments from patients with cystitis and bladder cancer. Author(s): Christensen M, Wolf H, Orntoft TF. Source: International Journal of Cancer. Journal International Du Cancer. 2000 March 1; 85(5): 614-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699938&dopt=Abstract

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Mixed connective tissue disease following interstitial cystitis. Author(s): Seishima M, Shimizu H, Oyama Z, Isogai K. Source: Eur J Dermatol. 2001 January-February; 11(1): 45-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174138&dopt=Abstract

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Modified urodynamics for interstitial cystitis. Author(s): Teichman JM, Nielsen-Omeis BJ, McIver BD. Source: Tech Urol. 1997 Summer; 3(2): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9297763&dopt=Abstract

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Molecular analysis of adrenergic receptor genes and interleukin-4/interleukin-4 receptor genes in patients with interstitial cystitis. Author(s): Sugaya K, Nishijima S, Yamada T, Miyazato M, Hatano T, Ogawa Y. Source: The Journal of Urology. 2002 December; 168(6): 2668-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442007&dopt=Abstract

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Mortality from grossly encrusted bilateral pyelitis, ureteritis, and cystitis by Corynebacterium group D2. Author(s): Chung SY, Davies BJ, O'Donnell WF. Source: Urology. 2003 February; 61(2): 463. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597981&dopt=Abstract

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Multiple urinary cytokine levels of bacterial cystitis. Author(s): Davidoff R, Yamaguchi R, Leach GE, Park E, Lad PM. Source: The Journal of Urology. 1997 May; 157(5): 1980-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9112576&dopt=Abstract

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Natural history of interstitial cystitis in 274 patients receiving sulfated polysaccharide therapy. Author(s): Ho NJ, Koziol JA, Parsons CL, Barlow W, Weiss NS. Source: Urology. 1999 June; 53(6): 1133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367841&dopt=Abstract

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New agents for the medical treatment of interstitial cystitis. Author(s): Theoharides TC, Sant GR. Source: Expert Opinion on Investigational Drugs. 2001 March; 10(3): 521-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11227050&dopt=Abstract

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New concepts in interstitial cystitis. Author(s): Parsons CL. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 1997; 8(1): 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9260088&dopt=Abstract

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Nitric oxide and interstitial cystitis. Author(s): Wein AJ. Source: The Journal of Urology. 1997 September; 158(3 Pt 1): 993. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9258128&dopt=Abstract

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Non-bacterial cystitis. Author(s): Hohlbrugger G, Riedl C. Source: Current Opinion in Urology. 2000 September; 10(5): 371-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005439&dopt=Abstract

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Nonbladder related symptoms in patients with interstitial cystitis. Author(s): Erickson DR, Morgan KC, Ordille S, Keay SK, Xie SX. Source: The Journal of Urology. 2001 August; 166(2): 557-61; Discussion 561-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11458068&dopt=Abstract

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Non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis. Author(s): Denton AS, Clarke NW, Maher EJ. Source: Cochrane Database Syst Rev. 2002; (3): Cd001773. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137633&dopt=Abstract

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Not so simple cystitis: how should prescribers be supported to make informed decisions about the increasing prevalence of infections caused by drug-resistant bacteria? Author(s): Davey P, Steinke D, MacDonald T, Phillips G, Sullivan F. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2000 February; 50(451): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10750215&dopt=Abstract

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Observations on the management of interstitial cystitis in men. Author(s): Forrest J, Vo Q. Source: Urology. 2001 June; 57(6 Suppl 1): 107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378071&dopt=Abstract

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Observations on the presentation, diagnosis, and treatment of interstitial cystitis in men. Author(s): Forrest JB, Vo Q. Source: Urology. 2001 June; 57(6 Suppl 1): 26-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378046&dopt=Abstract

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Obstructive uropathy due to interstitial cystitis in a patient with systemic lupus erythematosus. Author(s): Kim HJ, Park MH. Source: Clinical Nephrology. 1996 March; 45(3): 205-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8706364&dopt=Abstract

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Oestrogen receptor status of mast cells in interstitial cystitis. Author(s): Harnden P, Southgate J. Source: British Journal of Urology. 1996 March; 77(3): 474-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8814870&dopt=Abstract

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Oral methotrexate in the management of refractory interstitial cystitis. Author(s): Moran PA, Dwyer PL, Carey MP, Maher CF, Radford NJ. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1999 November; 39(4): 468-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10687766&dopt=Abstract

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Outcome after hyperbaric oxygen treatment for cyclophosphamide-induced refractory hemorrhagic cystitis. Author(s): Kalayoglu-Besisik S, Abdul-Rahman IS, Erer B, Yenerel MN, Oguz FS, Tunc M, Sargin D. Source: The Journal of Urology. 2003 September; 170(3): 922. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913734&dopt=Abstract

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Over expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in patients with interstitial cystitis and bladder carcinoma. Author(s): Ueda T, Tamaki M, Ogawa O, Yoshimura N. Source: The Journal of Urology. 2002 January; 167(1): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743354&dopt=Abstract

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Overexpression of platelet-derived endothelial cell growth factor (PD-ECGF) factor/thymidine phosphorylase (TP) in interstitial cystitis. Author(s): Ueda T, Tamaki M, Ogawa O, Yoshimura N. Source: Urology. 2001 June; 57(6 Suppl 1): 130-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378130&dopt=Abstract

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Overrepresentation of point mutations in the Sp1 site of the non-coding control region of BK virus in bone marrow transplanted patients with haemorrhagic cystitis. Author(s): Priftakis P, Bogdanovic G, Kalantari M, Dalianis T. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2001 April; 21(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255092&dopt=Abstract

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Overview of infection, immunology, and interstitial cystitis in the bladder. Author(s): Ratliff TL. Source: Advances in Experimental Medicine and Biology. 1999; 462: 323-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599435&dopt=Abstract

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Pain and depression experienced by women with interstitial cystitis. Author(s): Rabin C, O'Leary A, Neighbors C, Whitmore K. Source: Women & Health. 2000; 31(4): 67-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310812&dopt=Abstract

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Pathophysiology of bacterial cystitis. Author(s): Roberts JA. Source: Advances in Experimental Medicine and Biology. 1999; 462: 325-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599436&dopt=Abstract

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Pathophysiology of interstitial cystitis. Author(s): Rosamilia A, Dwyer PL, Dwyera PL. Source: Current Opinion in Obstetrics & Gynecology. 2000 October; 12(5): 405-10. Review. Erratum In: Curr Opin Obstet Gynecol 2001 April; 13(2): 253. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11111883&dopt=Abstract

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Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome. Author(s): Weiss JM. Source: The Journal of Urology. 2001 December; 166(6): 2226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696740&dopt=Abstract

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Pelvic lipomatosis associated with proliferative cystitis occurring in two brothers. Author(s): Tong RS, Larner T, Finlay M, Agarwal D, Costello AJ. Source: Urology. 2002 April; 59(4): 602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927334&dopt=Abstract

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Pelvic lipomatosis associated with proliferative cystitis: case report and review of the Japanese literature. Author(s): Masumori N, Tsukamoto T. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 1999 January; 6(1): 44-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221865&dopt=Abstract

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Percutaneous sacral nerve root neuromodulation for intractable interstitial cystitis. Author(s): Maher CF, Carey MP, Dwyer PL, Schluter PL. Source: The Journal of Urology. 2001 March; 165(3): 884-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176493&dopt=Abstract

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Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Author(s): Zermann DH, Ishigooka M, Schubert J. Source: Urology. 2001 January; 57(1): 207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245151&dopt=Abstract

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Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Author(s): Chai TC, Zhang C, Warren JW, Keay S. Source: Urology. 2000 May; 55(5): 643-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10792070&dopt=Abstract

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Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis. Author(s): Warren JW, Horne LM, Hebel JR, Marvel RP, Keay SK, Chai TC. Source: The Journal of Urology. 2000 June; 163(6): 1685-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799160&dopt=Abstract

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Pitfalls in the design of clinical trials for interstitial cystitis. Author(s): Propert KJ, Payne C, Kusek JW, Nyberg LM. Source: Urology. 2002 November; 60(5): 742-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429288&dopt=Abstract

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Potassium leak test predicts outcome in interstitial cystitis. Author(s): Teichman JM, Nielsen-Omeis BJ. Source: The Journal of Urology. 1999 June; 161(6): 1791-4; Discussion 1794-6. Erratum In: J Urol 1999 August; 162(2): 503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332436&dopt=Abstract

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Potential role of rel/nuclear factor-kappaB in the pathogenesis of interstitial cystitis. Author(s): Abdel-Mageed AB, Ghoniem GM. Source: The Journal of Urology. 1998 December; 160(6 Pt 1): 2000-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9817309&dopt=Abstract

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Practice guidelines for the treatment of uncomplicated cystitis. Author(s): Warren JW. Source: Curr Urol Rep. 2001 August; 2(4): 326-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084260&dopt=Abstract

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Practice trends for the management of interstitial cystitis. Author(s): Gershbaum D, Moldwin R. Source: Urology. 2001 June; 57(6 Suppl 1): 119. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378100&dopt=Abstract

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Preliminary study on urinary cytokine levels in interstitial cystitis: does intravesical bacille Calmette-Guerin treat interstitial cystitis by altering the immune profile in the bladder? Author(s): Peters KM, Diokno AC, Steinert BW. Source: Urology. 1999 September; 54(3): 450-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10475352&dopt=Abstract

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Prevalence of symptoms related to interstitial cystitis in women: a population based study in Finland. Author(s): Leppilahti M, Tammela TL, Huhtala H, Auvinen A. Source: The Journal of Urology. 2002 July; 168(1): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050508&dopt=Abstract

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Prognosis of conservative therapy of advanced interstitial cystitis: experience of five cases. Author(s): Yamada T, Murayama T. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2001 December; 8(12): 669-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851766&dopt=Abstract

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Prolonged hydrodistention of the bladder for symptomatic treatment of interstitial cystitis: efficacy at 6 months and 1 year. Author(s): Glemain P, Riviere C, Lenormand L, Karam G, Bouchot O, Buzelin JM. Source: European Urology. 2002 January; 41(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999471&dopt=Abstract

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Psychometric validation of the O'leary-Sant interstitial cystitis symptom index in a clinical trial of pentosan polysulfate sodium. Author(s): Lubeck DP, Whitmore K, Sant GR, Alvarez-Horine S, Lai C. Source: Urology. 2001 June; 57(6 Suppl 1): 62-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378052&dopt=Abstract

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Quality of life among women with interstitial cystitis. Author(s): Michael YL, Kawachi I, Stampfer MJ, Colditz GA, Curhan GC. Source: The Journal of Urology. 2000 August; 164(2): 423-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10893601&dopt=Abstract

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Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. Author(s): Leung AY, Suen CK, Lie AK, Liang RH, Yuen KY, Kwong YL. Source: Blood. 2001 September 15; 98(6): 1971-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535537&dopt=Abstract

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Radiation-induced haemorrhagic cystitis. Author(s): Crew JP, Jephcott CR, Reynard JM. Source: European Urology. 2001 August; 40(2): 111-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528186&dopt=Abstract

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Re: A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. Author(s): Riedl CR, Hohlbrugger G. Source: The Journal of Urology. 2000 December; 164(6): 2029-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061916&dopt=Abstract

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Re: A randomized double-blind trial of oral l-arginine for treatment of interstitial cystitis. Author(s): Brown TM. Source: The Journal of Urology. 2000 November; 164(5): 1666. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11025740&dopt=Abstract

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Re: Crew JP, Jephcott CR, Reynard JM. Radiation-induced haemorrhagic cystitis. Eur Urol 2001;40(2):111-23. Author(s): Duggan B, Nambirajan T, Johnston SR. Source: European Urology. 2003 March; 43(3): 323. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600438&dopt=Abstract

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Re: Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation. Author(s): Zermann DH, Schubert J, Ishigooka M, Schmidt RA. Source: The Journal of Urology. 1999 September; 162(3 Pt 1): 807-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458382&dopt=Abstract

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Re: Diurnal cortisol variations and symptoms in patients with interstitial cystitis. Author(s): Buffington T. Source: The Journal of Urology. 2002 November; 168(5): 2132. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394737&dopt=Abstract

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Re: Editorial: Interstitial cystitis--a light at the end of the tunnel? Author(s): Rosamilia A, Dwyer P. Source: The Journal of Urology. 2000 April; 163(4): 1257. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737517&dopt=Abstract

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Re: Epidemiology of interstitial cystitis: a population based study. Author(s): Ratner V, Taylor N, Wein AJ, Hanno PJ. Source: The Journal of Urology. 1999 August; 162(2): 500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10411074&dopt=Abstract

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Re: Percutaneous sacral nerve root neuromodulation for intractable interstitial cystitis. Author(s): Chai TC. Source: The Journal of Urology. 2001 September; 166(3): 1009. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490282&dopt=Abstract

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Re: The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database Study. Author(s): Zermann DH, Wunderlich H, Schubert J, Ishigooka M. Source: The Journal of Urology. 1999 September; 162(3 Pt 1): 807. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458381&dopt=Abstract

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Re: The efficacy of intravesical bacillus Calmette-Guerin in the treatment of interstitial cystitis: long-term followup. Author(s): Irwin PP. Source: The Journal of Urology. 1998 December; 160(6 Pt 1): 2163. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9817356&dopt=Abstract

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Re: The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. Author(s): Chambers GK, Fenster H. Source: The Journal of Urology. 1999 May; 161(5): 1581-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210413&dopt=Abstract

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Recent developments in the management of interstitial cystitis. Author(s): Bouchelouche K, Nordling J. Source: Current Opinion in Urology. 2003 July; 13(4): 309-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811295&dopt=Abstract

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Recombinant human nerve growth factor in the treatment of interstitial cystitis: preliminary results. Author(s): Dimitrakov J, Tchitalov J, Zlatanov T, Dikov D, Rawadi G. Source: Urology. 2001 June; 57(6 Suppl 1): 118-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378099&dopt=Abstract

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Recruitment, distribution and phenotypes of mast cells in interstitial cystitis. Author(s): Peeker R, Enerback L, Fall M, Aldenborg F. Source: The Journal of Urology. 2000 March; 163(3): 1009-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10688040&dopt=Abstract

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Recurrent cystitis in nonpregnant women. Author(s): Chew LD, Fihn SD. Source: The Western Journal of Medicine. 1999 May; 170(5): 274-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10379218&dopt=Abstract

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Recurrent cystitis in non-pregnant women. Author(s): Cooper B, Jepson R. Source: Clin Evid. 2002 June; (7): 1764-71. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230787&dopt=Abstract

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Recurrent eosinophilic cystitis with peripheral eosinophilia and hyperimmunoglobulinemia E. Author(s): Matsuura H, Sakurai M, Arima K. Source: Urologia Internationalis. 2003; 70(4): 327-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740501&dopt=Abstract

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Reducing consultations for symptoms of cystitis using a health education leaflet. Author(s): Banks JC, Howie JG. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1998 September; 48(434): 1595-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9830186&dopt=Abstract

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Risk factors for severe hemorrhagic cystitis following BMT. Author(s): Seber A, Shu XO, Defor T, Sencer S, Ramsay N. Source: Bone Marrow Transplantation. 1999 January; 23(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10037048&dopt=Abstract

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Sacral nerve stimulation for pain relief in interstitial cystitis. Author(s): Zermann DH, Weirich T, Wunderlich H, Reichelt O, Schubert J. Source: Urologia Internationalis. 2000; 65(2): 120-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11025436&dopt=Abstract

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Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study. Author(s): Comiter CV. Source: The Journal of Urology. 2003 April; 169(4): 1369-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629364&dopt=Abstract

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Safety and efficacy of up to 900 mg/day polysulfate sodium (elmiron) in patients with interstitial cystitis. Author(s): Nickel JC, Forrest J, Barkin J, Payne C, Mosbaugh P. Source: Urology. 2001 June; 57(6 Suppl 1): 122-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378111&dopt=Abstract

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Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor as urine markers for interstitial cystitis. Author(s): Keay SK, Zhang CO, Shoenfelt J, Erickson DR, Whitmore K, Warren JW, Marvel R, Chai T. Source: Urology. 2001 June; 57(6 Suppl 1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378043&dopt=Abstract

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Serum amyloid A: a novel serum marker for the detection of systemic inflammatory response in cystitis. Author(s): Lannergard A, Friman G, Larsson A. Source: The Journal of Urology. 2003 September; 170(3): 804-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913703&dopt=Abstract

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Short-term therapy of acute uncomplicated cystitis. Author(s): Naber KG. Source: Current Opinion in Urology. 1999 January; 9(1): 57-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10726073&dopt=Abstract

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Significance of hematuria in patients with interstitial cystitis: review of radiographic and endoscopic findings. Author(s): Gomes CM, Sanchez-Ortiz RF, Harris C, Wein AJ, Rovner ES. Source: Urology. 2001 February; 57(2): 262-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182333&dopt=Abstract

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Similarities between interstitial cystitis and male chronic pelvic pain syndrome. Author(s): Moldwin RM. Source: Curr Urol Rep. 2002 August; 3(4): 313-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149163&dopt=Abstract

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Soft-tissue case 31. Emphysematous cystitis. Author(s): Cheng CW, Lee DW, Chan PS. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2000 February; 43(1): 14, 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714250&dopt=Abstract

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Sonographic detection of emphysematous cystitis. Author(s): Choong KK. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2003 August; 22(8): 847-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901415&dopt=Abstract

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Spontaneous bladder rupture due to chronic cystitis 20 years after cystolithotomy. Author(s): Gogus C, Turkolmez K, Savas B, Sertcelik A, Baltaci S. Source: Urologia Internationalis. 2002; 69(4): 327-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444296&dopt=Abstract

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Stress and symptomatology in patients with interstitial cystitis: a laboratory stress model. Author(s): Lutgendorf SK, Kreder KJ, Rothrock NE, Ratliff TL, Zimmerman B. Source: The Journal of Urology. 2000 October; 164(4): 1265-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992377&dopt=Abstract

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Stress and symptoms in patients with interstitial cystitis: a life stress model. Author(s): Rothrock NE, Lutgendorf SK, Kreder KJ, Ratliff T, Zimmerman B. Source: Urology. 2001 March; 57(3): 422-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248609&dopt=Abstract

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Stretch-activated release of adenosine triphosphate by bladder uroepithelia is augmented in interstitial cystitis. Author(s): Sun Y, Keay S, DeDeyne P, Chai T. Source: Urology. 2001 June; 57(6 Suppl 1): 131. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378132&dopt=Abstract

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Subtotal cystectomy with ileocystoplasty for severe hemorrhagic cystitis after bone marrow transplantation. Author(s): Sebe P, Garderet L, Traxer O, Nouri M, Gluckman E, Gattegno B. Source: Urology. 2001 January; 57(1): 168. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164170&dopt=Abstract

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Subtypes of bladder mast cells in interstitial cystitis. Author(s): Yamada T, Murayama T, Mita H, Akiyama K. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2000 August; 7(8): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976817&dopt=Abstract

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Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation. Author(s): Hattori K, Yabe M, Matsumoto M, Kudo Y, Yasuda Y, Inoue H, Minami S, Miyakita H, Kawamura N, Komori K, Yamamoto I, Yabe H. Source: Bone Marrow Transplantation. 2001 June; 27(12): 1315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548852&dopt=Abstract

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Successful treatment of severe hemorrhagic cystitis with cystectomy following matched donor allogeneic hematopoietic cell transplantation. Author(s): Koc S, Hagglund H, Ireton RC, Perez-Simon JA, Collins SJ, Appelbaum FR. Source: Bone Marrow Transplantation. 2000 October; 26(8): 899-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081392&dopt=Abstract

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Surgical treatment of interstitial cystitis in women. Author(s): Hohenfellner M, Black P, Linn JF, Dahms SE, Thuroff JW. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 2000; 11(2): 113-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10805269&dopt=Abstract

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Symptom reports among interstitial cystitis patients. Author(s): Stoney C, Bonfiglio D, Buffington T, Woodworth B. Source: Urology. 2001 June; 57(6 Suppl 1): 127. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378122&dopt=Abstract

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The diagnosis and treatment of interstitial cystitis. Author(s): Peters KM. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2000 April; 20(2): 101-7, 131. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998120&dopt=Abstract

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The efficacy of chondroitin sulfate 0.2% in treating interstitial cystitis. Author(s): Steinhoff G, Ittah B, Rowan S. Source: Can J Urol. 2002 February; 9(1): 1454-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886599&dopt=Abstract

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The evil twins of chronic pelvic pain syndrome: endometriosis and interstitial cystitis. Author(s): Chung MK, Chung RR, Gordon D, Jennings C. Source: Jsls. 2002 October-December; 6(4): 311-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500828&dopt=Abstract

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The impact of empirical management of acute cystitis on unnecessary antibiotic use. Author(s): McIsaac WJ, Low DE, Biringer A, Pimlott N, Evans M, Glazier R. Source: Archives of Internal Medicine. 2002 March 11; 162(5): 600-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871930&dopt=Abstract

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The optimal use of diagnostic testing in women with acute uncomplicated cystitis. Author(s): Bent S, Saint S. Source: Disease-A-Month : Dm. 2003 February; 49(2): 83-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601339&dopt=Abstract

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The optimal use of diagnostic testing in women with acute uncomplicated cystitis. Author(s): Bent S, Saint S. Source: The American Journal of Medicine. 2002 July 8; 113 Suppl 1A: 20S-28S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113868&dopt=Abstract

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The prevalence of interstitial cystitis in gynecologic patients with pelvic pain, as detected by intravesical potassium sensitivity. Author(s): Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Willems JJ. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 1395400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439537&dopt=Abstract

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The role of self-help groups in educating and supporting patients with prostate cancer and interstitial cystitis. Author(s): Breau RH, Norman RW. Source: Bju International. 2003 October; 92(6): 602-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511043&dopt=Abstract

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Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. Author(s): Peeker R, Fall M. Source: The Journal of Urology. 2002 June; 167(6): 2470-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992059&dopt=Abstract

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Treatment for interstitial cystitis. Author(s): Buffington CA. Source: Urology. 2002 November; 60(5): 939; Author Reply 939-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429342&dopt=Abstract

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Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen. Author(s): Corman JM, McClure D, Pritchett R, Kozlowski P, Hampson NB. Source: The Journal of Urology. 2003 June; 169(6): 2200-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771749&dopt=Abstract

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Upper renal tract deterioration after cyclophosphamide-induced cystitis: the case for monitoring after cyclophosphamide therapy. Author(s): Sweeney JP, Fan CW, Keogh JA, Thornhill JA. Source: British Journal of Urology. 1998 April; 81(4): 639-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9598647&dopt=Abstract

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Urinary bacterial flora of women with urethral syndrome and interstitial cystitis. Author(s): Haarala M, Kiilholma P, Lehtonen OP. Source: Gynecologic and Obstetric Investigation. 1999; 47(1): 42-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9852391&dopt=Abstract

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Urinary levels of substance P and its metabolites are not increased in interstitial cystitis. Author(s): Campbell DJ, Tenis N, Rosamilia A, Clements JA, Dwyer PL. Source: Bju International. 2001 January; 87(1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121990&dopt=Abstract

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Urinary substance P concentration correlates with urinary frequency and urgency in interstitial cystitis patients treated with intravesical dimethyl sulfoxide and not intravesical anesthetic cocktail. Author(s): Kushner L, Chiu PY, Brettschneider N, Lipstein A, Eisenberg E, Rofeim O, Moldwin R. Source: Urology. 2001 June; 57(6 Suppl 1): 129. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378126&dopt=Abstract

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Urine autoantibodies in interstitial cystitis. Author(s): Keay S, Zhang CO, Trifillis AL, Hebel JR, Jacobs SC, Warren JW. Source: The Journal of Urology. 1997 March; 157(3): 1083-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9072548&dopt=Abstract

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Urine markers of interstitial cystitis. Author(s): Erickson DR. Source: Urology. 2001 June; 57(6 Suppl 1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378044&dopt=Abstract

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Urodynamic results of intravesical heparin therapy for women with frequency urgency syndrome and interstitial cystitis. Author(s): Kuo HC. Source: J Formos Med Assoc. 2001 May; 100(5): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11432309&dopt=Abstract

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Urological treatment and clinical course of BK polyomavirus-associated hemorrhagic cystitis in children after bone marrow transplantation. Author(s): Vogeli TA, Peinemann F, Burdach S, Ackermann R. Source: European Urology. 1999 September; 36(3): 252-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10450012&dopt=Abstract

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Urothelial cytoprotective activity of Tamm-Horsfall protein isolated from the urine of healthy subjects and patients with interstitial cystitis. Author(s): Akiyama A, Stein PC, Houshiar A, Parsons CL. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2000 May; 7(5): 176-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830825&dopt=Abstract

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Use of the neodymium: YAG laser for interstitial cystitis: a prospective study. Author(s): Rofeim O, Hom D, Freid RM, Moldwin RM. Source: The Journal of Urology. 2001 July; 166(1): 134-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435840&dopt=Abstract

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Vesical necrosis after hydrodistension of the urinary bladder in a patient with interstitial cystitis. Author(s): Grossklaus DJ, Franke JJ. Source: Bju International. 2000 July; 86(1): 140-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10886099&dopt=Abstract

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Vidarabine therapy for virus-associated cystitis after allogeneic bone marrow transplantation. Author(s): Kawakami M, Ueda S, Maeda T, Karasuno T, Teshima H, Hiraoka A, Nakamura H, Tanaka K, Masaoka T. Source: Bone Marrow Transplantation. 1997 September; 20(6): 485-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9313882&dopt=Abstract

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Virulence factors and O groups of Escherichia coli isolates from patients with acute pyelonephritis, cystitis and asymptomatic bacteriuria. Author(s): Blanco M, Blanco JE, Alonso MP, Blanco J. Source: European Journal of Epidemiology. 1996 April; 12(2): 191-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8817199&dopt=Abstract

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Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies. Author(s): Hukkanen V, Haarala M, Nurmi M, Klemi P, Kiilholma P. Source: Urological Research. 1996; 24(4): 235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8873382&dopt=Abstract

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Xanthogranulomatous cystitis as a cause of elevated carcinoembryonic antigen mimicking recurrent colorectal cancer. Report of a case. Author(s): Garcia AA, Florentine BD, Simons AJ, Skinner EC, Leichman LW. Source: Diseases of the Colon and Rectum. 1996 September; 39(9): 1051-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8797658&dopt=Abstract

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Xanthogranulomatous cystitis associated with anaerobic bacterial infection. Author(s): Tai HL, Chen CC, Yeh KT. Source: The Journal of Urology. 1999 September; 162(3 Pt 1): 795-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458373&dopt=Abstract

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Xanthogranulomatous cystitis associated with malignant neoplasms of the bladder. Author(s): Bates AW, Fegan AW, Baithun SI. Source: Histopathology. 1998 September; 33(3): 212-5. Erratum In: Histopathology 1998 December; 33(6): 590. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9777386&dopt=Abstract

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CHAPTER 2. NUTRITION AND CYSTITIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and cystitis.

Finding Nutrition Studies on Cystitis 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 “cystitis” (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 “cystitis” (or a synonym): •

A deficit of chondroitin sulfate proteoglycans on the bladder uroepithelium in interstitial cystitis. Author(s): Department of Urology, College of Medicine, Oklahoma University Health Sciences Center, Oklahoma City, USA. Source: Hurst, R E Roy, J B Min, K W Veltri, R W Marley, G Patton, K Shackelford, D L Stein, P Parsons, C L Urology. 1996 November; 48(5): 817-21 0090-4295

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A randomized double-blind placebo-controlled crossover trial of the efficacy of Larginine in the treatment of interstitial cystitis. Author(s): Pyrah Department of Urology, St James's University Hospital, Leeds, UK. [email protected] Source: Cartledge, J J Davies, A M Eardley, I BJU-Int. 2000 March; 85(4): 421-6 1464-4096

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Aluminum toxicity following intravesical alum irrigation for hemorrhagic cystitis. Author(s): Department of Hematology Oncology, St. Jude Children's Research Hospital, Mcmphis, TN 38101-0318, USA. Source: Kanwar, V S Jenkins, J J Mandrell, B N Furman, W L Med-Pediatr-Oncol. 1996 July; 27(1): 64-7 0098-1532

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An investigation of the nature of bladder mucosal glycoconjugates and their role in interstitial cystitis. Author(s): Department of Biochemistry, M S Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA. Source: Bhavanandan, V P Erickson, D R Indian-J-Biochem-Biophys. 1997 Feb-April; 34(1-2): 205-11 0301-1208

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Antibiotic treatment for five days is effective in children with acute cystitis. Author(s): Department of Paediatric Surgery, The Queen Silvia Children 's Hospital, Goteborg, Sweden. [email protected] Source: Abrahamsson, K Hansson, S Larsson, P Jodal, U Acta-Paediatr. 2002; 91(1): 55-8 0803-5253

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Calcium signaling in cultured human detrusor smooth muscle cells from patients with interstitial cystitis. Author(s): Department of Urology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. Source: Bouchelouche, K Horn, T Nordling, J Larsen, S Hald, T Bouchelouche, P Urology. 2001 June; 57(6 Suppl 1): 109-10 1527-9995

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Control of persistent vesical bleeding due to radiation cystitis by intravesical application of 15 (S) 15-methyl prostaglandin F2-alpha. Source: Hemal, A K Praveen, B V Sankaranarayanan, A Vaidyanathan, S Indian-JCancer. 1989 June; 26(2): 99-101 0019-509X

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Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents. Author(s): Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy. Source: Maggi, C A Lecci, A Santicioli, P Del Bianco, E Giuliani, S J-Auton-Nerv-Syst. 1992 May 15; 38(3): 201-8 0165-1838

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Cyclophosphamide-induced cystitis in rats: involvement of capsaicin-sensitive primary afferents. Author(s): Pharmacol. Department, A Menarini Pharmaceuticals, Florence, Italy.

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Source: Maggi, C A Lecci, A Santicioli, P Del Bianco, E Giuliani, S Agents-Actions. 1993; 38 Spec NoC28-30 0065-4299 •

Cystitis and nonsteroidal antiinflammatory drugs: an incidental association or an adverse effect? Author(s): National Toxicology Group, University of Otago Medical School, Dunedin. Source: Ghose, K N-Z-Med-J. 1993 November 24; 106(968): 501-3 0028-8446

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Effects of AH-9700, (+)-pentazocine, DTG and oxybutynin on micturition in anesthetized rats with acetone-induced cystitis. Author(s): Department of Pharmacology 1, Dainippon Pharmaceutical Co., Ltd., Suita/Osaka, Japan. [email protected] Source: Shimizu, I Kawashima, K Ishii, D Oka, M Life-Sci. 2001 August 24; 69(14): 1691-7 0024-3205

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Effects of L-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis. Author(s): Department of Urology, Karolinska Hospital, Stockholm, Sweden. Source: Ehren, I Lundberg, J O Adolfsson, J Wiklund, N P Urology. 1998 December; 52(6): 1026-9 0090-4295

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Effects of resiniferatoxin on the neurogenic component of feline interstitial cystitis. Author(s): Department of Veterinary Clinical Sciences, Ohio State University, Columbus, Ohio, USA. Source: March, P Teng, B Westropp, J Buffington, T Urology. 2001 June; 57(6 Suppl 1): 114 1527-9995

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Encouraging results in the treatment of haemorrhagic cystitis with estrogen - report of 10 cases and review of the literature. Author(s): Department of Medicine I, Technical University of Dresden, University Hospital 'Carl Gustav Carus', Dresden, Germany. Source: Ordemann, R Naumann, R Geissler, G Bornhauser, M Schuler, U Ehninger, G Bone-Marrow-Transplant. 2000 May; 25(9): 981-5 0268-3369

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Eosinophilic cystitis presenting as urinary retention. Author(s): Department of Urology, St. Clara Hospital Rotterdam, Rotterdam, The Netherlands. Source: van den Ouden, D van Kaam, N Eland, D Urol-Int. 2001; 66(1): 22-6 0042-1138

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Epithelial coating techniques in the treatment of interstitial cystitis. Author(s): Division of Urology, University of California at San Diego Medical Center, USA. Source: Parsons, C L Urology. 1997 May; 49(5A Suppl): 100-4 0090-4295

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Evaluation of effects of chitosan in preventing hemorrhagic cystitis in rats induced by cyclophosphamide. Author(s): Department of Urology, Nagoya City University Medical School. Source: Okamura, T Masui, T St John, M K Cohen, S M Taylor, R J Hinyokika-Kiyo. 1995 April; 41(4): 289-96 0018-1994

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Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome. Source: Russell, A L Med-Hypotheses. 1999 April; 52(4): 297-301 0306-9877

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Interstitial cystitis provoked by tiaprofenic acid. Author(s): Department of Urology, Gentofte University Hospital, Copenhagen, Denmark.

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Source: Schou, J Jensen, H L Frimodt Moller, C Scand-J-Urol-Nephrol. 1999 December; 33(6): 411-2 0036-5599 •

Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. Author(s): Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston. Source: Ippoliti, C Przepiorka, D Mehra, R Neumann, J Wood, J Claxton, D Gajewski, J Khouri, I van Besien, K Andersson, B et al. Urology. 1995 December; 46(6): 811-5 00904295

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Intravesicular instillation of E-aminocaproic acid for patients with adenovirusinduced hemorrhagic cystitis. Author(s): Rush Cancer Institute, Rush University, Chicago, IL, USA. Source: Lakhani, A Raptis, A Frame, D Simpson, D Berkahn, L Mellon Reppen, S Klingemann, H Bone-Marrow-Transplant. 1999 December; 24(11): 1259-60 0268-3369

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Long-term results of trigone-preserving orthotopic substitution enterocystoplasty for interstitial cystitis. Author(s): Department of Urology, Universitatsklinikum Munster, Munster, Germany. Source: van Ophoven, Arndt Oberpenning, Frank Hertle, Lothar J-Urol. 2002 February; 167(2 Pt 1): 603-7 0022-5347

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Nalmefene in the treatment of interstitial cystitis. Author(s): Department of Urology, Mt. Sinai School of Medicine, New York, New York. Source: Stone, N N Urol-Clin-North-Am. 1994 February; 21(1): 101-6 0094-0143

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Non-urotoxic induction of hemorrhagic cystitis by braxin C, a bracken toxin, in guinea pigs. Author(s): Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, Japan. Source: Yoshida, M Saito, T J-Toxicol-Sci. 1994 May; 19(2): 55-9 0388-1350

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Pelvic lipomatosis associated with proliferative cystitis: case report and review of the Japanese literature. Author(s): Department of Urology, Hikkaido Health Insurance Central Hospital and Sapporo Medical University School of Medicine, Japan. [email protected] Source: Masumori, N Tsukamoto, T Int-J-Urol. 1999 January; 6(1): 44-9 0919-8172

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Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats. Author(s): Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida 33328, USA. Source: Xu, X Malave, A Pharmacol-Toxicol. 2001 May; 88(5): 232-7 0901-9928

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Self-care strategies used for acute attack of interstitial cystitis. Source: Webster, D C Brennan, T Urol-Nurs. 1995 September; 15(3): 86-93 1053-816X

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Sonography of cyclophosphamide hemorrhagic cystitis: a report of two cases. Author(s): Department of Radiology, School of Medicine, Tokyo Medical and Dental University, Japan. Source: Suzuki, T Yasumoto, M Shibuya, H Suzuki, S J-Clin-Ultrasound. 1988 Mar-April; 16(3): 183-6 0091-2751

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Successful treatment of hemorrhagic cystitis secondary to cyclophosphamide chemotherapy with intravesical instillation of prostaglandin F2 alpha. Author(s): Department of Urology, Nagoya University School of Medicine.

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Source: Yamamoto, M Hibi, H Ohmura, M Miyake, K Hinyokika-Kiyo. 1994 September; 40(9): 833-5 0018-1994 •

The contribution of sensory nerves to xylene-induced cystitis in rats. Author(s): Pharmacology Department, A. Menarini, Pharmaceuticals, Florence, Italy. Source: Maggi, C A Abelli, L Giuliani, S Santicioli, P Geppetti, P Somma, V Frilli, S Meli, A Neuroscience. 1988 August; 26(2): 709-23 0306-4522

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The efficacy of chondroitin sulfate 0.2% in treating interstitial cystitis. Author(s): Department of Urology, Capital Health Region, Victoria, BC, Canada. Source: Steinhoff, G Ittah, B Rowan, S Can-J-Urol. 2002 February; 9(1): 1454-8 1195-9479

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The prevalence of interstitial cystitis in gynecologic patients with pelvic pain, as detected by intravesical potassium sensitivity. Author(s): Division of Urology, University of California San Diego Medical Center, 92103-8897, USA. [email protected] Source: Parsons, C L Dell, J Stanford, E J Bullen, M Kahn, B S Willems, J J Am-J-ObstetGynecol. 2002 November; 187(5): 1395-400 0002-9378

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Tiaprofenic acid-induced cystitis--three cases and a literature review. Author(s): Department of Urology, Frederiksberg Hospital, University of Copenhagen, Frederiksberg, Denmark. Source: Andreassen, K H Eldrup, J Hansen, R I Oster, S Scand-J-Urol-Nephrol. 1999 December; 33(6): 408-10 0036-5599

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Traditional Chinese medicine syndromes in women with frequently recurring cystitis: frequencies of syndromes and symptoms. Author(s): Bryggen Medical Centre, Bergen, Norway. [email protected] Source: Alraek, T Aune, A Baerheim, A Complement-Ther-Med. 2000 December; 8(4): 260-5 0965-2299

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Treatment of cyclophosphamide-induced hemorrhagic cystitis with prostaglandins. Author(s): Division of Pharmacy, University of Texas M.D. Anderson Cancer Center, Houston 77030. Source: Miller, L J Chandler, S W Ippoliti, C M Ann-Pharmacother. 1994 May; 28(5): 5904 1060-0280

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Treatment of interstitial cystitis with a quercetin supplement. Author(s): Division of Urology, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, California, USA. Source: Katske, F Shoskes, D A Sender, M Poliakin, R Gagliano, K Rajfer, J Tech-Urol. 2001 March; 7(1): 44-6 1079-3259

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Treatments used in women with interstitial cystitis: the interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group. Author(s): University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. Source: Rovner, E Propert, K J Brensinger, C Wein, A J Foy, M Kirkemo, A Landis, J R Kusek, J W Nyberg, L M Urology. 2000 December 20; 56(6): 940-5 1527-9995

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Urinary tract infection: traditional pharmacologic therapies. Author(s): Department of Internal Medicine, University of Manitoba, Winnipeg, Canada. Source: Nicolle, Lindsay E Am-J-Med. 2002 July 8; 113 Suppl 1A: 35S-44S 0002-9343

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Urine markers of interstitial cystitis. Author(s): Department of Surgery, Division of Urology, Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, USA. [email protected] Source: Erickson, D R Urology. 2001 June; 57(6 Suppl 1): 15-21 1527-9995

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Urodynamics in acetone-induced cystitis of anesthetized rats. Author(s): Department of Pharmacology 1, Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Suita/Osaka, Japan. [email protected] Source: Shimizu, I Kawashima, K Hosoki, K Neurourol-Urodyn. 1999; 18(2): 115-27 0733-2467

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Vitamins Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html

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Minerals Sodium Bicarbonate Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com

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Food and Diet Berries Source: Healthnotes, Inc.; www.healthnotes.com Cinnamon Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,271,00.html Cranberries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,144,00.html

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Juices Source: Healthnotes, Inc.; www.healthnotes.com Natural Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Pumpkin Seeds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,176,00.html Refined Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Sugar Alcohols Source: Healthnotes, Inc.; www.healthnotes.com

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

'An empty and happy feeling in the bladder.': health changes experienced by women after acupuncture for recurrent cystitis. Author(s): Alraek T, Baerheim A. Source: Complementary Therapies in Medicine. 2001 December; 9(4): 219-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184349&dopt=Abstract

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Attempted reversal of oxytetracycline resistance of Proteus mirabilis by EDTAtromethamine lavage in experimentally induced canine and feline cystitis. Author(s): Wooley RE, Blue JL, Campbell LM. Source: Am J Vet Res. 1975 October; 36(10): 1533-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=811139&dopt=Abstract

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Botanical perspectives on health: of cystitis and cranberries. Author(s): Patel N, Daniels IR.

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Source: J R Soc Health. 2000 March; 120(1): 52-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918785&dopt=Abstract •

Caring for the patient with interstitial cystitis. Author(s): Kaufman MW, All AC, Hall N, Clark JY. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 1997 August; 6(4): 203-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9313547&dopt=Abstract

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Comparison of the uroprotective efficacy of mesna and HBO treatments in cyclophosphamide-induced hemorrhagic cystitis. Author(s): Etlik O, Tomur A, Deveci S, Piskin I, Pekcan M. Source: The Journal of Urology. 1997 December; 158(6): 2296-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366379&dopt=Abstract

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Conservative management of chronic interstitial cystitis: transcutaneous electrical nerve stimulation and transurethral resection. Author(s): Fall M. Source: The Journal of Urology. 1985 May; 133(5): 774-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3872946&dopt=Abstract

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Current controversies that adversely affect interstitial cystitis patients. Author(s): Ratner V. Source: Urology. 2001 June; 57(6 Suppl 1): 89-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378055&dopt=Abstract

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Efficacy of EDTA-tris-lysozyme lavage in the treatment of experimentally in induced Pseudomonas aeruginosa cystitis in the dog. Author(s): Wooley RE, Schall WD, Eagon RG, Scott TA. Source: Am J Vet Res. 1974 January; 35(1): 27-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4203507&dopt=Abstract

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Evaluation of transvaginal theile massage as a therapeutic intervention for women with interstitial cystitis. Author(s): Holzberg A, Kellog-Spadt S, Lukban J, Whitmore K. Source: Urology. 2001 June; 57(6 Suppl 1): 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378103&dopt=Abstract

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Fishbein/interstitial cystitis association (ICA) survey of interstitial cystitis among family members of ICA members: preliminary analysis. Author(s): Warren J, Jackson T, Meyers D, Xu J.

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Source: Urology. 2001 June; 57(6 Suppl 1): 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378121&dopt=Abstract •

Haemorrhagic cystitis complicating cyclophosphamide treatment in children. Author(s): Helin I, Okmian L. Source: Acta Paediatr Scand. 1973 September; 62(5): 497-500. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4585165&dopt=Abstract

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Hemorrhagic cystitis after i.v. bleomycin, vinblastine, cisplatin, and etoposide for testicular cancer. Author(s): Cantwell BM, Harris AL, Patrick D, Hall RR. Source: Cancer Treat Rep. 1986 April; 70(4): 548-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2421895&dopt=Abstract

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Hemorrhagic cystitis associated with BKV in patients with refractory acute lymphoblastic leukemia. Author(s): Azzi A, Ciappi S, De Santis R, Fanci R, Leoni F, Colli S, Rossi-Ferrini PL. Source: American Journal of Hematology. 1996 June; 52(2): 121-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8638636&dopt=Abstract

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Hemorrhagic cystitis associated with turpentine ingestion. Author(s): Klein FA, Hackler RH. Source: Urology. 1980 August; 16(2): 187. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7404916&dopt=Abstract

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Hemorrhagic cystitis with MOPP therapy. Author(s): Royal JE, Seeler RA. Source: Cancer. 1978 April; 41(4): 1261-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=638990&dopt=Abstract

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Hemorrhagic cystitis, chemotherapy, and bladder toxicity. Author(s): Ratliff TR, Williams RD. Source: The Journal of Urology. 1998 March; 159(3): 1044. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9474228&dopt=Abstract

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Hyperbaric oxygen for cyclophosphamide-induced cystitis. Author(s): Hughes MJ, Davis FM, Mark SD, Spearing RL. Source: British Journal of Haematology. 2002 November; 119(2): 575. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406105&dopt=Abstract

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Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis. Author(s): Hughes AJ, Schwarer AP, Millar IL.

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Source: Bone Marrow Transplantation. 1998 September; 22(6): 585-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9758348&dopt=Abstract •

Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis. Author(s): Shameem IA, Shimabukuro T, Shirataki S, Yamamoto N, Maekawa T, Naito K. Source: European Urology. 1992; 22(3): 263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1468485&dopt=Abstract

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Hyperbaric oxygen therapy for pediatric hemorrhagic cystitis. Author(s): Furness PD 3rd, Palmer LS, Palmer JS, Capelli-Schellpfeffer M, Cheng EY. Source: The Journal of Urology. 1999 May; 161(5): 1596-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210424&dopt=Abstract

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Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis. Author(s): Mathews R, Rajan N, Josefson L, Camporesi E, Makhuli Z. Source: The Journal of Urology. 1999 February; 161(2): 435-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9915420&dopt=Abstract

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Hyperbaric oxygen therapy for Wegener's granulomatosis with cyclophosphamideinduced hemorrhagic cystitis. Author(s): Kuroda I, Kuwata Y, Kakehi Y. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2002 August; 9(8): 470-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225346&dopt=Abstract

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Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Author(s): Bevers RF, Bakker DJ, Kurth KH. Source: Lancet. 1995 September 23; 346(8978): 803-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7674746&dopt=Abstract

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Hyperbaric oxygenation therapy for cyclophosphamide-induced haemorrhagic cystitis. Author(s): Yazawa H, Nakada T, Sasagawa I, Miura M, Kubota Y. Source: International Urology and Nephrology. 1995; 27(4): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8586509&dopt=Abstract

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Interstitial cystitis or reflex sympathetic dystrophy of the bladder? Author(s): Galloway NT, Gabale DR, Irwin PP.

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Source: Semin Urol. 1991 May; 9(2): 148-53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1853012&dopt=Abstract •

Interstitial cystitis. Author(s): Allan E. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1998 June 10-16; 12(38): 43-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9775911&dopt=Abstract

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Interstitial cystitis. Author(s): Melson G. Source: Ostomy Wound Manage. 1993 January-February; 39(1): 52-4, 56, 58. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8452623&dopt=Abstract

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Interstitial cystitis. A patient's perspective. Author(s): Ratner V, Slade D, Greene G. Source: The Urologic Clinics of North America. 1994 February; 21(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284831&dopt=Abstract

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Is the diet of patients with interstitial cystitis related to their disease? Author(s): Bade JJ, Peeters JM, Mensink HJ. Source: European Urology. 1997; 32(2): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9286650&dopt=Abstract

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Management of ischemic hemorrhagic cystitis with hyperbaric oxygen therapy. Author(s): Lopez AE, Rodriguez S, Flores I. Source: Undersea & Hyperbaric Medicine : Journal of the Undersea and Hyperbaric Medical Society, Inc. 2001 Spring; 28(1): 35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732883&dopt=Abstract

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Outcome after hyperbaric oxygen treatment for cyclophosphamide-induced refractory hemorrhagic cystitis. Author(s): Kalayoglu-Besisik S, Abdul-Rahman IS, Erer B, Yenerel MN, Oguz FS, Tunc M, Sargin D. Source: The Journal of Urology. 2003 September; 170(3): 922. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913734&dopt=Abstract

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Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome. Author(s): Weiss JM.

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Source: The Journal of Urology. 2001 December; 166(6): 2226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696740&dopt=Abstract •

Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Author(s): Zermann DH, Ishigooka M, Schubert J. Source: Urology. 2001 January; 57(1): 207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245151&dopt=Abstract

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Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Author(s): Chai TC, Zhang C, Warren JW, Keay S. Source: Urology. 2000 May; 55(5): 643-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10792070&dopt=Abstract

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Potentiating effect of EDTA-Tris on the activity of antibiotics against resistant bacteria associated with otitis, dermatitis and cystitis. Author(s): Farca AM, Piromalli G, Maffei F, Re G. Source: The Journal of Small Animal Practice. 1997 June; 38(6): 243-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9200113&dopt=Abstract

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Prevention of further cyclophosphamide induced hemorrhagic cystitis by hyperbaric oxygen and mesna in guinea pigs. Author(s): Korkmaz A, Oter S, Deveci S, Goksoy C, Bilgic H. Source: The Journal of Urology. 2001 September; 166(3): 1119-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490309&dopt=Abstract

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Psychosomatic “cystitis”. Author(s): SMITH DR. Source: The Journal of Urology. 1962 March; 87: 359-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13914194&dopt=Abstract

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Psychosomatic “cystitis”. Author(s): SMITH DR. Source: Trans Am Assoc Genitourin Surg. 1961; 53: 113-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14039368&dopt=Abstract

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Recontextualizing sexuality in chronic illness: women and interstitial cystitis. Author(s): Webster DC.

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Source: Health Care for Women International. 1997 November-December; 18(6): 575-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9416041&dopt=Abstract •

Sacral nerve stimulation for pain relief in interstitial cystitis. Author(s): Zermann DH, Weirich T, Wunderlich H, Reichelt O, Schubert J. Source: Urologia Internationalis. 2000; 65(2): 120-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11025436&dopt=Abstract

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Self-care strategies used for acute attack of interstitial cystitis. Author(s): Webster DC, Brennan T. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 1995 September; 15(3): 86-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7481892&dopt=Abstract

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Sonographic findings in a case of postradiation hemorrhagic cystitis resolved by hyperbaric oxygen therapy. Author(s): Huang WC, Yang JM. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2003 September; 22(9): 967-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510269&dopt=Abstract

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Sonography of cyclophosphamide hemorrhagic cystitis: a report of two cases. Author(s): Suzuki T, Yasumoto M, Shibuya H, Suzuki S. Source: Journal of Clinical Ultrasound : Jcu. 1988 March-April; 16(3): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3150400&dopt=Abstract

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Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation. Author(s): Hattori K, Yabe M, Matsumoto M, Kudo Y, Yasuda Y, Inoue H, Minami S, Miyakita H, Kawamura N, Komori K, Yamamoto I, Yabe H. Source: Bone Marrow Transplantation. 2001 June; 27(12): 1315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548852&dopt=Abstract

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Successful treatment of radiation cystitis with hyperbaric oxygen. Author(s): Rijkmans BG, Bakker DJ, Dabhoiwala NF, Kurth KH. Source: European Urology. 1989; 16(5): 354-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2776806&dopt=Abstract

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The cure of recurrent cystitis. Author(s): Gould RS.

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Source: Jama : the Journal of the American Medical Association. 1972 July 17; 221(3): 304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5067804&dopt=Abstract •

The effect of prophylactic acupuncture treatment in women with recurrent cystitis: kidney patients fare better. Author(s): Alraek T, Baerheim A. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2003 October; 9(5): 651-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629843&dopt=Abstract

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The role of self-help groups in educating and supporting patients with prostate cancer and interstitial cystitis. Author(s): Breau RH, Norman RW. Source: Bju International. 2003 October; 92(6): 602-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511043&dopt=Abstract

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The treatment of “interstitial cystitis” as a migraine equivalent: report of four cases. Author(s): COHEN RL. Source: Comprehensive Psychiatry. 1963 February; 4: 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14022089&dopt=Abstract

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The treatment of “interstitial cystitis” as a migraine equivalent: report of four cases. Author(s): COHEN RL. Source: Comprehensive Psychiatry. 1963 February; 4: 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14022088&dopt=Abstract

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Therapy in cytoxan hemorrhagic cystitis. Author(s): Pauwels RP, Moonen WA. Source: Urologia Internationalis. 1970; 25(2): 187-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5422716&dopt=Abstract

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Traditional acupuncture and electrical stimulation of the posterior tibial nerve. A trial in chronic interstitial cystitis. Author(s): Geirsson G, Wang YH, Lindstrom S, Fall M. Source: Scandinavian Journal of Urology and Nephrology. 1993; 27(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8493470&dopt=Abstract

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Traditional Chinese medicine syndromes in women with frequently recurring cystitis: frequencies of syndromes and symptoms. Author(s): Alraek T, Aune A, Baerheim A.

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Source: Complementary Therapies in Medicine. 2000 December; 8(4): 260-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098202&dopt=Abstract •

Transcutaneous electrical nerve stimulation in classic and nonulcer interstitial cystitis. Author(s): Fall M, Lindstrom S. Source: The Urologic Clinics of North America. 1994 February; 21(1): 131-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284836&dopt=Abstract

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Transcutaneous electrical nerve stimulation in interstitial cystitis. Update on clinical experience. Author(s): Fall M. Source: Urology. 1987 April; 29(4 Suppl): 40-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3494331&dopt=Abstract

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Treatment guidelines for classic and non-ulcer interstitial cystitis. Author(s): Peeker R, Fall M. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 2000; 11(1): 23-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10738931&dopt=Abstract

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Treatment of interstitial cystitis with a quercetin supplement. Author(s): Katske F, Shoskes DA, Sender M, Poliakin R, Gagliano K, Rajfer J. Source: Tech Urol. 2001 March; 7(1): 44-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272677&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

General Overview Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Benign Prostatic Hyperplasia Source: Healthnotes, Inc.; www.healthnotes.com Bladder Infection Alternative names: Urinary Tract Infection [UTI] Source: Prima Communications, Inc.www.personalhealthzone.com Bladder Infection and Inflammation Source: Integrative Medicine Communications; www.drkoop.com Diverticular Disease Source: Integrative Medicine Communications; www.drkoop.com Edema Source: Healthnotes, Inc.; www.healthnotes.com Gallstones Source: Prima Communications, Inc.www.personalhealthzone.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Infection Source: Healthnotes, Inc.; www.healthnotes.com Kidney Stones Source: Integrative Medicine Communications; www.drkoop.com

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Pelvic Inflammatory Disease Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer 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 Reiter's Syndrome Source: Integrative Medicine Communications; www.drkoop.com Urinary Incontinence Source: Integrative Medicine Communications; www.drkoop.com Urinary Tract Infection Source: Healthnotes, Inc.; www.healthnotes.com Urinary Tract Infection in Women Source: Integrative Medicine Communications; www.drkoop.com UTI Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Acupuncture Source: Healthnotes, Inc.; www.healthnotes.com Hydrotherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,705,00.html

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Chinese Medicine Ershiwuwei Songshi Wan Alternative names: Ershiwuwei Songshi Pills (Used by Tibetan Nationality); Ershiwuwei Songshi Wan (Er Shi Wu Wei Song Shi Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China

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Lidan Paishi Pian Alternative names: Lidan Paishi Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Shisanwei Bangga San Alternative names: Shisanwei Bangga Powder; Shisanwei Bangga San
(Shi San Wei Banq Qa San) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China •

Homeopathy Aconitum Napellus Source: Healthnotes, Inc.; www.healthnotes.com Apis Mellifica Source: Healthnotes, Inc.; www.healthnotes.com Belladonna Source: Healthnotes, Inc.; www.healthnotes.com Berberis Vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Borax Source: Healthnotes, Inc.; www.healthnotes.com Cantharis 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 Nux Vomica Source: Healthnotes, Inc.; www.healthnotes.com Sarsaparilla Source: Healthnotes, Inc.; www.healthnotes.com Sepia Source: Healthnotes, Inc.; www.healthnotes.com Staphysagria Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Achillea Alternative names: Yarrow; Achillea millefolium L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Acidophilus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,748,00.html Arctostaphylos Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Arginine Source: Healthnotes, Inc.; www.healthnotes.com Barberry Alternative names: Berberis vulgaris, Berberry Source: Integrative Medicine Communications; www.drkoop.com Bayberry Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Bearberry Source: Integrative Medicine Communications; www.drkoop.com Beargrape Source: Integrative Medicine Communications; www.drkoop.com Berberis Vulgaris Source: Integrative Medicine Communications; www.drkoop.com Berberry Source: Integrative Medicine Communications; www.drkoop.com Bilberry Alternative names: Vaccinium myrtillus Source: Healthnotes, Inc.; www.healthnotes.com Bilberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10007,00.html Blueberry Alternative names: Vaccinium spp. Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Source: Healthnotes, Inc.; www.healthnotes.com

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Buchu Alternative names: Barosma betulina, Agathosma betulina, Agathosma crenultata Source: Healthnotes, Inc.; www.healthnotes.com Butcher's Broom Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10010,00.html Calendula Alternative names: Calendula officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cleavers Alternative names: Galium aparine Source: Healthnotes, Inc.; www.healthnotes.com Cleavers Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Coleus Forskohlii Source: Prima Communications, Inc.www.personalhealthzone.com Corn Silk Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Cranberry Alternative names: Vaccinium macrocarpon Source: Healthnotes, Inc.; www.healthnotes.com Cranberry Alternative names: Vaccinium macrocarpon Source: Integrative Medicine Communications; www.drkoop.com Cranberry Source: Prima Communications, Inc.www.personalhealthzone.com Cranberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10019,00.html Damiana Source: Prima Communications, Inc.www.personalhealthzone.com DMSO Source: Healthnotes, Inc.; www.healthnotes.com

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Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,775,00.html Echinacea Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea Pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea Purpurea Source: Integrative Medicine Communications; www.drkoop.com Golden Rod Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Goldenrod Source: Prima Communications, Inc.www.personalhealthzone.com Goldenseal Alternative names: Hydrastis canadensis Source: Healthnotes, Inc.; www.healthnotes.com Goldenseal Source: Prima Communications, Inc.www.personalhealthzone.com Goldenseal Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,791,00.html Gravel Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Greater Celandine Alternative names: Chelidonium majus Source: Healthnotes, Inc.; www.healthnotes.com Horseradish Alternative names: Cochlearia armoracia Source: Healthnotes, Inc.; www.healthnotes.com

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Horsetail Alternative names: Equisetum arvense Source: Healthnotes, Inc.; www.healthnotes.com Horsetail Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10105,00.html Hydrangea Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hyoscyamine Source: Healthnotes, Inc.; www.healthnotes.com Juniper Alternative names: Juniperus communis Source: Healthnotes, Inc.; www.healthnotes.com Juniper Berries Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Juniper Berry Source: Prima Communications, Inc.www.personalhealthzone.com L. Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Lactobacillus Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Lapacho Source: Prima Communications, Inc.www.personalhealthzone.com Marshmallow Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Methionine Source: Prima Communications, Inc.www.personalhealthzone.com MSM Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,807,00.html

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Nettle Alternative names: Urtica dioica Source: Healthnotes, Inc.; www.healthnotes.com Nettle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10048,00.html Oregon Grape Alternative names: Berberis aquifolium Source: Healthnotes, Inc.; www.healthnotes.com Parsley Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,869,00.html Phenazopyridine Source: Healthnotes, Inc.; www.healthnotes.com Plantain Alternative names: Plantago lanceolata, Plantago major Source: Healthnotes, Inc.; www.healthnotes.com Plantain Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Sandalwood Alternative names: Santalum album Source: Healthnotes, Inc.; www.healthnotes.com Saw Palmetto Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,819,00.html Trimethoprim Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim/sulfamethoxazole Alternative names: Bactrim, Cotrim, Septra, Sulfatrim Source: Prima Communications, Inc.www.personalhealthzone.com Uva Ursi Alternative names: Arctostaphylos uva-ursi Source: Healthnotes, Inc.; www.healthnotes.com

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Uva Ursi Alternative names: Arctostaphylos uva ursi, Bearberry, Beargrape Source: Integrative Medicine Communications; www.drkoop.com Uva Ursi Source: Prima Communications, Inc.www.personalhealthzone.com Uva Ursi Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10063,00.html Vaccinium Macrocarpon Source: Integrative Medicine Communications; www.drkoop.com Yarrow Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca

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. CLINICAL TRIALS AND CYSTITIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning cystitis.

Recent Trials on Cystitis The following is a list of recent trials dedicated to cystitis.8 Further information on a trial is available at the Web site indicated. •

Interstitial Cystitis Condition(s): Interstitial Cystitis Study Status: This study is currently recruiting patients. Sponsor(s): ICOS Purpose - Excerpt: Patients with interstitial cystitis who meet eligibility requirements will be randomized to one of four treatment arms (3 RTX, Placebo). Study drug is administered as a single instillation within the urinary bladder. Study duration is 12 weeks. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056251

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ORWH:SCOR - Sex/Gender Factors Affecting Women's Health Condition(s): Urinary Tract Infection Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

8

These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: This project is the clinical project of a Specialized Center of Research (SCOR) proposal which is designed to further our understanding of urinary tract infection (UTI) in women. Acute uncomplicated urinary tract infections (UTIs) occur in an estimated 7-11 million women each year, and the annual costs of caring for these women are thought to approach $1.6 billion. Approximately 20-30% of women suffer from frequent recurrent infections. UTIs in young women result in substantial symptoms, time lost from work, and medical costs. An improved understanding of the mechanisms underlying UTIs could result in new approaches to their prevention and reduced numbers of women with infections and the amount of antibiotics use. In this project we seek a better understanding of the causes of UTI. Most experts believe that vaginal colonization with UTI-causing bacteria from the rectal flora precedes colonization of the urethra (the tube from the bladder for urination) and bladder and subsequent UTI, but the relationships between these events has not been established. Moreover, recent information from studies in mice strongly suggest that persistent bladder infection follows an initial bladder infection. In this project, we will prospectively follow a large group of women with recurrent UTI to determine: 1) the relationships in time between vaginal colonization with a UTI-causing bacteriuria, asymptomatic bacteriuria (bacteria in the bladder but without any UTI symptoms) and symptomatic UTI, and 2) the presence of persistent bacteria in the bladder following the symptomatic UTI at entry into the study and whether such bacteria are related to later UTIs that are caused by the same bacteria that caused the UTI at entry into the study. We will thus be able to determine the relative importance of vaginal colonization vs. persistent infection of the bladder as the origin of the bacteria causing recurrent UTI. UTI-causing bacteria cultured from women with symptomatic UTI and asymptomatic bacteriuria will undergo studies by Dr. Scott Hultgren's group at Washington University in Project 1 to identify unique genes that may help us understand why some bacteria cause symptoms and others do not. The effect of bacteria causing UTI in these women on host response will also be determined by studies by Dr. Jeff Gordon's laboratory at Washington University in Project 3. A better understanding of the molecular and epidemiologic basis of UTI is critical in developing the best possible prevention and management strategies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068120 •

UTI Prophylaxis Using Bacterial Interference Following SCI Condition(s): Urinary Tract Infections Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Rehabilitation Research and Development Service Purpose - Excerpt: Urinary tract infection (UTI) is the most common infection in patients with SCI and is a major cause of morbidity and mortality in this population. The bladder of patients with SCI, especially those who have indwelling catheters, is often colonized by bacteria that may or may not cause symptoms of UTI. Bacteria that do not cause symptoms are usually considered benign colonizers and are often left untreated because they may afford some protection against symptomatic infection with more harmful bacteria. We applied the concept of using benign bacteria to prevent symptomatic infection, so-called bacterial interference, by deliberately colonizing the bladder of patients with SCI with a non-pathogenic prototype of Escherichia coli (strain 83972). The

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preliminary results of our VA-funded study that compared the rates of symptomatic UTI in patients with SCI while colonized with E. coli 83972 vs. historical rates of symptomatic UTI prior to study enrollment indicated that deliberate colonization of the bladder of patients with SCI with E. coli 83972 is safe and very promising as to its ability to prevent symptomatic UTI. However, before this innovative approach of bacterial interference can be successfully applied in the population of patients with SCI, it is essential to: (A) confirm the ultimate efficacy of bacterial interference by conducting a prospective, randomized, placebo-controlled clinical trial (objective #1); and (B) enhance the practicality of applying this innovative approach in SCI patients by delineating the bacterial and host factors that can promote successful colonization with E. coli 83972 (objectives #2-3). Phase(s): Phase II Study Type: Interventional Contact(s): Rabih Darouiche, M.D. 713-794-7117 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00037921

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 5. PATENTS ON CYSTITIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “cystitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on cystitis, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Cystitis By performing a patent search focusing on cystitis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

9Adapted

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

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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 cystitis: •

Antiproliferative factor from patients with interstitial cystitis Inventor(s): Hise; Michael K. (Ellicott City, MD), Keay; Susan (Ellicott City, MD), Kleinberg; Michael (Baltimore, MD), Warren; John W. (Baltimore, MD) Assignee(s): University of Maryland (Baltimore, MD) Patent Number: 5,962,645 Date filed: October 3, 1997 Abstract: A novel antiproliferative factor (APF) present in urine of patients with interstitial cystitis (IC) is described. This urine antiproliferative factor can serve as a marker for disease activity and its antagonists as therapeutic medicaments for IC. In addition, APF and its agonists can be used for treating diseases associated with cell proliferation. Excerpt(s): Interstitial cystitis (IC) is a chronic bladder disorder which affects up to 450,000 women in the United States; approximately one-tenth as many men also suffer from this condition ›Ratner, et al. (1994) Urol. Clin. North Am. 21:1-5; Hanno et al. (1990) Interstitial Cystitis, London: Springer-Verlag!. Interstitial cystitis often has a rapid onset with pain, urgency and frequency of urination and cystoscopic abnormalities including petechial hemorrhages (glomerulations) or ulcers that extend into the lamina propria (Hunner's ulcers) ›Oravisto, K. J. (1975) Ann. Chir. Gynaecol. Fenn. 64: 75!. Certain features of the bladder epithelium suggest that the epithelial barrier is abnormal in IC. For example, the bladder mucin layer is sometimes damaged ›Johansson and Fall (1990) J. Urol. 143:1118; Smith and Dehner (1972) Arch. Pathol. 93:76!, the bladder epithelium can be denuded resulting in ulceration ›Oravisto, ibid; Smith, ibid! and intraurothelial Tamm-Horsfall protein is sometimes found ›Fowler et al. (1988) J. Urol. 140:1385!. The rapid onset of IC is followed by a chronic course with partial remissions and reexacerbations, which can continue for up to 30 years ›Hanno, ibid.! No etiology for IC has yet been identified, and no empiric treatment has been proven to be reliably efficacious. The diagnosis of IC currently requires cystoscopy and bladder biopsy, with either of two distinct mucosal abnormalities (Hunner's ulcers or glomerulations) being diagnostic of this disorder. Therefore, there is a need for a faster, less invasive method for diagnosing IC in patients. Web site: http://www.delphion.com/details?pn=US05962645__

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Apparatus and method for non-invasively detecting urinary tract infection using ultrasound Inventor(s): McMorrow; Gerald J. (Kirkland, WA) Assignee(s): Diagnostic Ultrasound Corporation (Redmond, WA) Patent Number: 5,592,941 Date filed: October 20, 1995 Abstract: An ultrasound signal is transmitted into the center of the bladder. The received backscatter information is gated so that the data which remains is from a sample volume within the bladder and does not include information from the front or back walls and surrounding tissues of the bladder. The backscatter information is then compared with a

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preestablished threshold value. If the received backscatter is above a threshold value, it is indicative of a possible urinary tract infection, and an alarm is transmitted to the user. Excerpt(s): This invention generally concerns body condition monitoring apparatus and more specifically concerns ultrasound monitoring of the condition of urine in the bladder as a way of detecting possible urinary tract infections. Bladder dysfunction is associated with frequent incidents of urinary tract infection. A person with bladder dysfunction, due to injury, disease, or other cause, is unable to readily detect a possible infection; accordingly, such persons are at high risk for urinary infections. Other persons also may have a high risk of urinary tract infection, due to other causes. There is now available non-invasive means for detecting the volume of urine in the bladder, which has been quite helpful for those persons with bladder dysfunction, due to which the fullness of the bladder cannot be physically detected by the person. Such non-invasive means are shown in U.S. Pat. No. 4,926,871 to Ganguly et al. and U.S. Pat. No. 5,235,985 to McMorrow et al. However, those devices are only capable of detecting urine volume in the bladder, and are not directed toward detection of possible infection. For those persons at high risk for urinary tract infection, especially those with significant bladder dysfunction, it would be desirable to have an early warning of impending urinary tract infection, i.e. an ability to detect infection at an early stage, at which point it can be more readily and inexpensively treated. Web site: http://www.delphion.com/details?pn=US05592941__ •

Compositions comprising nitrofurantoin and uva ursi Inventor(s): Charbonneau; Duane Larry (Lebanon, OH), Taylor; Kevin Douglas (Mason, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 6,521,270 Date filed: May 7, 2002 Abstract: Compositions and kits comprising nitrofurantoin and uva ursi are effective for treating infectious disorders, particularly urinary tract infections, cystitis, and pyclonephritis. Excerpt(s): The present invention relates to compositions and kits useful in treating infectious disorders. Urinary tract infections (UTI) are a serious health problem affecting millions of people each year. UTI infections account for about 10 million doctor visits in the United States alone, with only respiratory infections occurring more often. Many remedies are taught for the treatment of UTI. In particular, nitrofurantoin is a wellknown antibacterial compound and has been used extensively as an active ingredient in antibacterial pharmaceutical compositions. Nitrofurantoin has been used successfully for many years for the treatment of UTI. Its presumed mode of action is based upon its interference with several bacterial enzyme systems. However, the development of antibiotic resistant strains of microbes continues to be problematic, thereby diminishing the effectiveness of many antibiotics. Web site: http://www.delphion.com/details?pn=US06521270__

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Compositions for treating Escherichia coli urinary tract infections Inventor(s): Hakomori; Sen-Itiroh (Mercer Island, WA), Nudelman; Edward (Seattle, WA), Stamm; Walter E. (Seattle, WA), Stapleton; Ann (Seattle, WA) Assignee(s): The Biomembrane Institute (Seattle, WA), The Regents of the University of Washington (Seattle, WA) Patent Number: 6,432,681 Date filed: July 9, 1999 Abstract: Compositions and methods for diagnosing, treating and preventing recurrent E. coli urinary tract infections relate to the detection and use of globosides, such as disialosyl galactosyl-globoside (DSGG) and sialosyl galactosyl-globoside (SGG), and stabilized forms thereof, such as those wherein sialic acid is replaced by KDN Excerpt(s): The instant invention relates to a method for determining susceptibility to Escherichia coli urinary tract infections (UTI) and corresponding methods for diagnosing secretors and nonsecretors of histo-blood group antigens based on assaying urogenital cells and secretions. The instant invention also relates to methods and compositions for preventing and treating E. coli urinary tract infections. For example, disialosyl galactosyl-globoside is useful for diagnostic purposes and sialosyl galactosylgloboside is useful for treatment and prevention of UTI. Among the most common bacterial infections encountered in clinical practice are urogenital mucosal infections caused by E. coli, Chiamydlia trachomatis and N. gonorrheae which are diagnosed and treated at a cost to society in the billions of dollars. These infections are frequently recurrent and efforts at prevention have been largely fruitless, in part because of the apparent ineffectiveness of the mucosal immune system. Mucosal immunity is shortlived and in the long term, not protective. Despite much effort, attempts to develop vaccines against these mucosal urogenital pathogens have not succeeded and even natural immunity does not protect against recurrent episodes of infection with these agents. In addition, antigenic variability of the organisms has complicated vaccine development. In particular, acute uncomplicated urinary tract infections occur in millions of young women each year. While most of these women experience only single or sporadic infections, approximately 20% suffer very frequent (.gtoreq.3/year) recurrences (Mabeck, C. E., Postgrad. Med J., 48:69-75, 1972). The apparent increased susceptibility to urinary tract infection in these patients cannot be explained by underlying functional or anatomic abnormalities of the urinary tract, but instead appears to arise from the interaction of infecting E. coli strains with these patients' epithelial cells. Web site: http://www.delphion.com/details?pn=US06432681__

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Cromolyn sodium containing composition and method of treatment for vilvar vestibulitis interstitial cystitis vukvar vaginitis and vaginitis dynea Inventor(s): Jones, III; Tudor (8745 Hampshire Glen Dr., Jacksonville, FL 32256) Assignee(s): none reported Patent Number: 6,225,356 Date filed: January 20, 2000 Abstract: A composition and method for the treatment of the conditions vulvar vestibulitis, interstitial cystitis, vulvar vaginitis or vaginitis dynea wherein a

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composition containing cromolyn sodium in effective amount is applied to the vaginal vestibule area, with the application repeated as necessary to effectively address the symptoms and conditions. Preferably, the cromolyn sodium is present in an amount of about 2 to 10 percent in a carrier ointment or cream, with the carrier composition preferably comprising a mixture of pluronic gel and lecithin organogel. Excerpt(s): This invention relates most generally to the field of therapeutic topical ointments containing cromolyn sodium and to therapeutic treatments for the pain and discomfort of such conditions as vulvar vestibulitis, interstitial cystitis, vulvar vaginitis or vaginitis dynea. Vulvar vestibulitis, interstitial cystitis, vulvar vaginitis and vaginitis dynea are relatively common conditions of the female vaginal, vulvar, and urinary areas, causing discomfort or pain during sexual intercourse or urination, or an increase in the frequency of urination. The conditions are believed to result from inflammation of specific areas. Typical anti-inflammatory treatments have proven ineffective against these conditions. Ineffective treatments for vulvar vestibulitis, which is localized in the vestibule area comprising the meeting point of the vulva and the vagina and which contains the Bartholin's glands, the urethra and minor vestibular glands, include steroid, zinc oxide and ketoconazole creams, as well as oatmeal sitz baths, calendula and hypercal creams, bland aqueous creams and the application of tea bags. Interstitial cystitis is a chronic inflammatory condition of the bladder wall and is not related to common cystitis, which is a urinary tract infection caused by bacteria. Interstitial cystitis is not caused by bacteria and does not respond to antibiotic therapy. Ineffective treatments include oral medications such as pentosan polysulfate sodium, tricyclic antidepressants, antispasmodics, antihistamines and muscle relaxants, as well as bladder distention and injection of dimethyl sulfoxide, heparin, silver nitrate, oxychlorosene sodium, bacillus Calmette-Guerin or hyaluronic acid. Cromolyn sodium is a known therapeutic composition which inhibits the degranulation of sensitized mast cells which occurs after exposure to specific antigens. The cromolyn inhibits the release of histamine and SRS-A (slow-reacting substance of anaphylaxis) from the mast cell. Some studies have shown that cromolyn further inhibits the degranulation of nonsensitized mast cells by phospholipase A and the subsequent release of chemical mediators, although contrary studies exist. Cromolyn has no intrinsic vasoconstrictor, antihistaminic or anti-inflammatory activity. Cromolyn sodium is well known in the treatment of certain conditions of the eye, such as vernal keratoconjunctivitis, vernal conjunctivitis and vernal keratitis, as well as in the treatment of certain allergic reactions and contact blepharitis. Cromolyn sodium is also used in the treatment of certain heart conditions, asthma, gastrointestinal conditions and skin conditions such as eczema or psoriasis. Cromolyn sodium has not been used in the treatment of vulvar vestibulitis, interstitial cystitis, vulvar vaginitis or vaginitis dynea. Web site: http://www.delphion.com/details?pn=US06225356__ •

Diagnostic test for interstitial cystitis Inventor(s): Elgavish; Ada (Birmingham, AL) Assignee(s): University of Alabama Research Foundation (Birmingham, AL) Patent Number: 5,824,493 Date filed: February 23, 1996 Abstract: A method of diagnosing interstitial cystitits in an individual and a kit for the method, comprising the steps of: obtaining primary cultures of urothelial cells; selecting urothelial cells of basal type and producing secondary cultures; measuring in secondary

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cultures (1) percentage of single cells and percentage of large colonies; (2) determining proliferative ability; (3) determining differentiation ability; (4) determining the percentage of large colonies that express phosphotyrosine and/or nitrotyrosine; (5) measuring the percentage of apoptotic cells; (6) measuring the percentage of large colonies; and (7) comparing the percentage of the colonies to baseline values of the same parameters determined in samples of similarly cultured urothelial cells taken from individuals not suspected of having interstitial cystitis. Excerpt(s): The present invention relates generally to the fields of urology, infectious diseases and diagnostic methodology. More specifically, the present invention relates to a novel diagnostic test for interstitial cystitis. Interstitial cystitis (IC) is a chronic disease of the bladder wall.sup.2,12,26,37,46. Distention at cystoscopy reveals scars, mucosal splittings and petechial hemorrhages.sup.20,27,40. Foci of urothelial detachment in bladders from patients with interstitial cystitis suggest that the architecture of the interstitial cystitis bladder urothelium is altered.sup.20. This possibility is further supported by classical studies relating dysfunction of the interstitial cystitis bladder mucosa with altered expression of proteoglycans on the surface of epithelial cells.sup.33,34. The etiology of interstitial cystitis is unknown. Its rapid onset, appearance in midlife, and absence of strong family association suggest that interstitial cystitis is an acquired disease, possibly caused by an infectious agent. The fact that 90% of interstitial cystitis patients are women parallels the epidemiology of bacterial urinary tract infections further supporting this possibility.sup.46. Web site: http://www.delphion.com/details?pn=US05824493__ •

Diagnostic test procedure for urinary tract inflammatory condition Inventor(s): Elgebaly; Salwa A. (Bloomfield, CT) Assignee(s): The University of Connecticut (Farmington, CT) Patent Number: 5,318,891 Date filed: July 8, 1992 Abstract: The invention provides a diagnostic test procedure for detecting the active status of interstitial cystitis, a chronic inflammatory disease of the bladder. Determination of chemotactic activity present in fluid that has been exposed to urinary tract tissue is performed by measuring cell migration across a membrane in response to neutrophil chemotactic factors in the fluid. Excerpt(s): present invention relates to a diagnostic test procedure for detecting the active status of a noninfectious inflammatory condition such as interstitial cystitis. Interstitial cystitis (IC) is a chronic debilitating inflammatory disorder of the bladder. The disease is most common in women ranging in age from about thirty to sixty with onset of the condition typically occurring at about forty years of age. The most prevalent symptoms include severe abdominal pain and urinary urgency two or three times per hour, day and night. The initiating causes are unknown and there is no known cure although alleviation of the symptoms can be obtained from selected treatment such as the use of dimethyl sulfoxide (DMSO). The condition is categorized as "interstitial cystitis" because it is believed the disease does not affect the surface of the bladder but instead involves the spaces between the cells, namely the interstices, in the lining of the bladder. Studies have indicated interstitial cystitis is not an auto-immune disease and no evidence exists that it is caused by infectious agents such as aerobic or anaerobic bacteria, viruses and the like. Accordingly, diagnosis is very difficult and treatments

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have met with limited success. It has been found that even a cystoscopic examination, which is the insertion of a long thin viewing instrument into the bladder, will not lead with certainty to a diagnosis. Diagnosis using biochemical and laboratory test also have not proved to be extremely helpful. A urine culture can be taken to determine if a bacterial infection is present and thereby rule out other diseases. If no infection or disease is found, a hydrodistentive cystoscopic examination can be carried out under anesthesia. In this procedure the bladder is stretched by filling it with irrigating fluid and the bladder wall is carefully examined cystoscopically. This is the only known way of detecting the characteristic mucosal abnormalities associated with interstitial cystitis, namely the tiny hemorrhages and scar tissue on the bladder wall. Since diagnosis can be uncertain even when using this highly invasive hydrodistention technique, other factors such as case history, urine analysis and culture, bladder biopsy and response to therapy all must also be taken into consideration for a proper diagnosis. Web site: http://www.delphion.com/details?pn=US05318891__ •

Fem-Ease, a supplement for the symptoms of cystitis, urinary tract infections and premenstrual syndrome Inventor(s): Stevenot; Robin Ann (P.O. Box 578487, Modesto, CA 95357-8487) Assignee(s): Stevenot; Robin Ann (Northbend, OR) Patent Number: 6,143,300 Date filed: August 11, 1998 Abstract: Over 450,000 women in the united states suffer from the medical disorder cystitis and several hundred in addition to this number, from urinary tract infections and premenstrual syndrome. Hundreds of clinical studies have shown the benefits of Kava Kava, Dandelion and L Arginine, each individually, as the relief for the many unpleasant symptoms that accompany cystitis, urinary tract infection and premenstrual syndrome. These beneficial results have been published in several prominent medical journals. Fem-Ease is a unique combination of all three ingredients together in one caplet. A light brown, cylinder shaped caplet with rounded corners, provides ease for the symptoms of cystitis, urinary tract infection and premenstrual syndrome. Two caplets in the morning and two caplets in the evening, provides a daily dose of 3000 mg of L Arginine, 790 mg of Kava Kava and 475 mg of Dandelion recommended to take at the first onset of symptoms. Excerpt(s): This invention relates to an herbal and amino acid supplement designed to ease the discomfort of cystitis, urinary tract infection and premenstrual syndrome. Medical doctors currently advise two types of treatments for cystitis: synthetic medications and surgery. Cystitis is inflammation of the bladder, usually occurring secondary to infections that involve associated organs (kidney, prostate, urethra). Lesion or ulcerative areas form in the lining of the bladder causing painful-frequent urination, abdominal pain, stress and severe depression. Cystitis sufferers find themselves frequenting the bathroom up to 60 times a day. The state of California provides permanent disability to women with long term documented histories of cystitis. Sufferers find themselves relying upon pain medications and antidepressants to get through the day. Work, relationships and normal daily activities become things of the past. Etiology of cystitis is still unknown. The four medications being used at this time to treat the symptoms of cystitis are Elmiron, DMSO, Hydroxyzine and Cystistat. These medications offer temporary relief but are not without side effects. Both DMSO and Cystistat are medications that need to be instilled into the bladder through means of

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catheterization. The user inserts a small flexible tube into the urethra and instills the medication into the bladder then holds it in as long as possible. Both of these medications attack the bacteria and free radical cells in the lining of the bladder then remove them as urination occurs. The method has been proven safe but with side effects. Those are: exacerbation of urinary frequency and urgency, odor, bladder irritation, bleeding of the gums and potential for increased infection during insertion of the catheter. The length of time the user holds the medication in, improves the benefits but is not worth the pain and discomfort. Treatment is 1-3 times a week for 2-4 months before symptoms begin to subside. Both Cystistat and DMSO are still in experimental stages. Medication costs are up to $200.00 per 4 installations a month plus $20.00 for FDA clearance fees. Additional treatments will cost up to $150.00 each. Elmiron and Hydroxyzine are two medications to be taken by mouth 1-3 times a day. Its is necessary to increase doses until adequate levels are reached in the body. This is estimated at 6-8 weeks. Elmiron has been shown to decrease the inflammation in the bladder wall reducing the symptoms of urination frequency and painful urination. Side effects may include hair loss, rash, head ache, swelling of the extremities, stomach upset and diarrhea. Hydroxyzine has been shown to decrease the histamine release in the body. Its benefits are unknown, yet cystitis sufferers have noticed some relief while taking this medication. Side effects are dry mouth , sedation, increased depression in patients diagnosed with concurrent depression and fetal abnormalities have been seen in animal studies. Medication costs are up to $160.00 for a one month supply. Taking these two drugs for eight weeks to four months may be required before reaching the maximum effect. Urinary tract infections (UTI) have been treated for years with the antibiotics Bactrim, Macrodantin and a combination of Sulfa drugs that offer quick relief, but for those sufferers of chronic UTI's these same antibiotics after several prescriptions become useless as the body forms a resistance to them. Side effects of these antibiotics include, and are limited to, body rash, abdominal pain, nausea, headache, lupus, shock, kidney disease, liver disease, lung disease, insomnia, weakness and rare deaths. Urinary tract infections are caused by germs that invade the tract causing symptoms of frequenturgent need to urinate, severe burning sensation upon urination, bloating or water retention and stress. Dietary changes and hygiene changes along with encouragement to drink 2000-3000 cc of water per day, that is twelve 8 oz glasses, leaves the sufferer full and visiting the bathroom too often to enjoy normal daily routines. UTI sufferers become dependent on pain relievers to alleviate the pain. Premenstrual Syndrome (PMS) is a combination of symptoms that for years have gone untreated. Symptoms occur a few days prior to onset of the menstrual cycle. Emotional unpredictability, depression, weight gain from fluid retention, breast tenderness and bouts of crying, anger and migraines headaches can be seen during this period. Over this past two decades, more attention has been focused on this condition. Antidepressant and mood elevators such as Prozac, Valium, Xanax, Elival, Zoloft and Effexor have been prescribed, more than any other class of medications in the USA, for the relief of symptoms. Yet most doctors will tell you this is a band-aid treatment. The side effects of these medications then requires additional medication. Side effects include but are not limited to, general malaise, insomnia, nervousness, dry mouth, headache, nausea, hallucinations, blurred vision, fast heart rate, chest pain and sexual dysfunction. The sufferers finds themselves lifeless and absent of normal emotions. Web site: http://www.delphion.com/details?pn=US06143300__

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H.sub.3 -receptor agonists as therapeutic agents Inventor(s): Theoharides; Theoharis C. (14 Parkman St., #2, Brookline, MA 02146) Assignee(s): none reported Patent Number: 5,821,259 Date filed: September 6, 1995 Abstract: The invention provides a method for preventing and alleviating the harmful biological effects of secretion of chemicals from mast cells in the organism of mammals which leads to clinical conditions namely allergy, asthma, arthritis, dermatitis, interstitial cystitis, inflammatory and irritable bowel disease, migraines, multiple sclerosis, scleroderma or systemic sclerosis, ulcerative disease of the gastro-intestinal tract and urticaria, among others. The method consists in administering to said mammals and especially to human beings an amount, effective against said conditions, of an H.sub.3 receptor agonist which has inhibitory activity of neurohormonal activation of mast cell secretion. Excerpt(s): The present invention relates to the use of histamine-3 (H.sub.3)-agonists as therapeutic agents with inhibitory activity of neurohormonal activation of mast cell secretion. It also relates to the use of pharmaceutical compositions containing such agonists as active ingredients. More particularly, the present invention pertains to a method of preventing or alleviating in mammals a disease characterized by an abnormally high number of mast cells, increased activation of mast cells or large amounts of mediators secreted therefrom by administering an H.sub.3 -agonist with inhibitory activity of neurohormonal activation of mast cell secretion. Histamine is a molecule found in many tissues where it can bind to specific receptors and lead to particular biologic actions. The histamine-1 (H.sub.1) receptor is found on vessels, and its activation leads to dilation and oedema; histamine-2 (H.sub.2) receptors are found on exocrine glands, such as the parietal cells in the stomach, where their activation leads to gastric acid secretion and ulcers. Recently, an H.sub.3 receptor was identified (Schwartz, J-C. Arrang, J. M., Garbarg, M. and Korner, M. Properties and roles of the three subclasses of histamine receptors in brain. J. Exp. Biol. 124:203-224, 1986) and seems to be involved in regulation of perivascular nerve activity (Ishikawa, S. and Sperelakis, N. A novel class (H.sub.3) of histamine receptors on perivascular nerve terminals. Nature 327:158-160, 1987). Prior art findings relate to the possible action of H.sub.3 -agonists to inhibit histamine release (Theoharides, T. C. Histamine.sub.2 (H.sub.2)-receptor antagonists in the treatment of urticaria. Drugs 37:345-355, 1989), to decrease bronchoconstriction (Ichinose, M. and Barnes, P. J. Histamine H3-receptors modulate nonadrenergic noncholinergic neural bronchoconstriction in guinea pig in vitro. Euro. J. Pharmacol. 174:49-55, 1989), or to increase the resistance of bronchial blood vessels and lower their permeability so that hemorrhagic phenomena due to vascular fragility will not occur (Ichinose, M., Belvisi, M. G. and Barnes, P. J. Histamine H3-receptors inhibit neurogenic microvascular leakage in airways. J. Appl. Physiol. 68:21-25, 1990). However, none of these findings lead one to the claims of this invention and a recent review of H.sub.3 -agonists does not mention any such claims as potential therapeutic prospects (Timmerman, H. Histamine H.sub.3 ligands: just pharmacological tools or potential therapeutic agents? J. Med. Chem. 33:4-11, 1990). Web site: http://www.delphion.com/details?pn=US05821259__

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Irrigation of internal bladder surfaces in mammals with sodium pentosanpolysulfate Inventor(s): Parsons; C. Lowell (San Diego, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,180,715 Date filed: July 31, 1989 Abstract: The method of treating bladder infections, interstitial cystitis and tumors in mammals which comprises the irrigation of the internal bladder and associated surfaces with an irrigating solution containing an effective amount of sodium pentosanpolysulfate. Also, the treatment of interstitial cystitis by the oral administration of sodium pentosanpolysulfate at high dosages on the order of 200 mg. per day or more. Excerpt(s): It has long been known that the urinary bladder in the normal state is remarkably resistant to infection, although little has been described concerning any intrinsic antibacterial defense mechanism. A vesical mucosal bactericidal activity has been suggested, Cobbs, G. C. and D. Kaye (1967)., "Antibacterial mechanisms in the urinary bladder", Yale J. Biol. Med. 40:93-108; Cox, C. E., and F. Hinman, Jr. (1961), "Experiments with induced bacteriuria, vesical emptying and bacterial growth on the mechanism of bladder defense to infection", J. Urol. 86:739-748;and Norden, C. W., G. M. Green, and E. H. Kass, (1968), "Antibacterial mechanisms of the urinary bladder", J. Clin. Invest. 47:2689-2700, but its existence has not been corroborated by other investigators, Mulholland, S. G., E. A. Foster, A. J. Paquin, Jr., and J. Y. Gillenwater (1969), "The effect of rabbit vesical mucosa on bacterial growth", Invest. Urol. 6:593-604. It seemed unlikely that chance alone accounted for the bladder's ability to maintain a sterile lumen in the face of direct contact with environmental organisms; rather, antibacterial defense mechanisms might actively maintain this equilibrium. In this regard, I became interested in the concept of bacterial virulence depending on the ability of bacteria to adhere to a mucous surface. Adherence has been postulated to play a role in bacterial virulence at many mucous surfaces including the gastrointestinal tract, the genitourinary tract, and the oral cavity, Ellen, R. P. and R. J. Gibbons (1972),"M protein-associated adherence of Streptococcus pyogenes to epithelial surfaces: prerequisite for virulence", Infect. Immuno. 5:826-830; Gibbons, R. J., and J. van Houte (1971), "Selective bacterial adherence to oral epithelial surfaces and its role as an ecological determinant", Infect. Immun. 3:567-573; Punsalong, A. P., Jr., and W. D. Sawyer (1973), "Role of pili in the virulence of Neisseria gonorrhoeae," Infect. Immun. 8:255-263; Sobelavsky. O., B. Prescott, and R. M. Chanock (1968), "Adsorption of Mycoplasma pneumoniae to neuraminic acid receptors of various cells and possible role in virulence", J. Bacteriol. 96:695-705; Svanborg-Eden, C., B. Eriksson, and L. A. Hanson (1977), "Adhesion of Escherichia coli to human uroepithelial cells in vitro", Infect. Immun. 18:767-774; Swanson, Jr. (1973), "Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells", J. Exp. Med. 137:571-589; Swanson, Jr., G. King, and B. Zeligs (1975), "Studies on gonococcus infection. VIII.sup.125 Iodine labeling of gonococci and studies on their in vitro interactions with eukaryotic cells", Infect. Immun. 11:453459; Ward, M. E., and P. J. Watt (1972), "Adherence of Neisseria gonorrhoeae to urethral mucosal cells: an electron-microscopic study of human gonorrhea", J. Infect. Dis. 126:601-605; and Ward, M. E., P. J. Watt, and J. N. Robertson (1974), "The human fallopian tube: a laboratory model for gonococcal infection", J. Infect. Dis. 129:650-659. The main theme of data obtained in these systems is that microbial ability to infect a surface is directly proportional to its ability to adhere to the mucosal cells. If adherence is important to bacterial virulence, it is possible that the body produces antiadherence factors as a counter measure. In the urinary bladder, an antiadherence factor preventing

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bacteria from adhering to the bladder wall would explain both the need for and the efficiency of the urine washout factor, Cox, C. E. and F. Hinman, Jr. (1961), "Experiments with induced bacteriuria, vesical emptying and bacterial growth on the mechanism of bladder defense to infection", J. Urol. 86:739-748. Human immonoglobulin A and glycoproteins have been studied as possible antiadherence factors acting in an antibodylike fashion, inactivating bacterial adherence mechanisms such as pili or the glycocalyx, Williams, R. C. and R. J. Gibbons (1972), "Inhibition of bacterial adherence by secretory immunoglobulin A: a mechanism of antigen disposal, "Science 177:697-699; Williams, R. C. and Gibbons, R. J.(1975), "Inhibition of streptococcal attachment to receptors on human buccal epithelia cells by antigenically similar salivary glycoproteins," Infect. Immuno. 11: 711-718. Such a mechanism would be less effective in the urinary bladder than at other mucous surfaces because it would require specific antibody production, which in turn requires prior exposure to antigens. Such a model does not adequately serve to explain the bladder's resistance to infection in the presence of a variety of environmental microorganisms. Web site: http://www.delphion.com/details?pn=US05180715__ •

Medical application for heparin and related molecules Inventor(s): Saliba, Jr.; Michael J. (5582 Thunderbird La., La Jolla, CA 92037) Assignee(s): none reported Patent Number: 4,879,282 Date filed: March 17, 1987 Abstract: New uses for heparin, or heparin-like compounds are described that encompass preserving and healing of cells and cell functions arising from transplantations, circumcisions, dermatitides, fissures, fistulas, stimulation of epithelial growth, keloid prevention, cold injuries, pathology and forensic diagnosis, myocardium, trauma, decubitus ulcers, psoriasis, poisonings, insect and snake bites, corrosive ingestions, the "bends," space-travel sickness, brain and heart nerve conduction electrical dysrhythmias, pulmonary respiratory distress, blood and blood products, ulcerative colon lesions, interstitial cystitis, and related cosmetic uses. The uses are realized by applying the compounds either in solution, or in the form of a cream or aerosol, preferably at a pH of about 5.5, in an effective amount and for a time sufficient to effect treatment. Generally, the concentration of heparin or heparin-like compounds will be in the range of 1500 to 5000 international units per milliliter. Clinical assays are also described for determining the amount of heparin that should be used in those instances where the effective concentration is not known. Excerpt(s): One of the major properties of heparin which has been recognized for some time is its ability to prolong the clotting time of blood both in vivo and in vitro. Less well known properties of heparin are that it stimulates healing of burn wounds and its ability to reverse ischemic myocardial injuries. For instance, Saliba et al. in J. Amer. Med. Assoc., 225, 261 (1973) describe the application of heparin-administered parenterally and topically to humans suffering from second and third degree burns. Heparin both relieves the pain and prevents the initial burn size from expanding. Most important, there is enhanced revascularization, granulation and re-epithelialization. The effect of heparin on burn wound healing is critically dose-related, dose-dependent and pH regulated (Saliba, Thrombosis and Haemostasis, 40, No. 1 (1978)). Most applications of heparin as a therapeutic agent have used concentrations in the range of 20,000 to 40,000 units/per milliliter for intravenous or subcutaneous modes of presentation, while

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for topical applications concentrations in the range of 5,000 to 10,000 units/per milliliter have been employed. The beneficial effect of heparin on reversing myocardial ischemic injury generally has been shown to require the administration of 10,000 to 100,000 units total of 5,000 to 10,000 units/ml heparin, with favorable results being apparent acutely on electrocardiograms and on cardiac enzymes monitored at 24 and 48 hours. In addition to the above effects of heparin, the molecule is also thought to exhibit antithrombin, antiplatelet-lysis, thrombolytic, antihistaminic, antiserotonin and antiproteolytic enzymatic activity. The mechanism whereby heparin exerts all these effects is not known. Lastly, heparin has also been shown to be effective in treating weeping poison oak dermatitis (Saliba and Griner Aerospace Medicine, 41, 2, 179 (1970)) and weeping ear eczema and acute tracheal bronchitis (Dougherty and Dolowitz, Amer. J. Cardiol. 14, 18 (1964)). The following U.S. patents show various medical applications for heparin or related compounds. U.S. Pat. No. 3,062,716 shows a method of treating hemorrhoids. U.S. Pat. No. 3,137,624 describes compositions for treating defective veins wherein one component is heparin. U.S. Pat. No. 3,244,594 describes heparin compounds having antitumor activity. U.S. Pat. No. 3,151,025 describes a composition that rids the blood of lipoprotein molecules. U.S. Pat. No. 4,039,665 shows a method of composition containing heparin for eradication of venous blemishes. Lastly, U.S. Pat. No. 4,390,532 shows another composition with heparin that is useful for topical applications in treating wrinkles, acne and androgen baldness. Web site: http://www.delphion.com/details?pn=US04879282__ •

Method and a removable device which can be used for the self-administered treatment of urinary tract infections or other disorders Inventor(s): Simon; John G. (Boston, MA) Assignee(s): UroMed Corporation (Watertown, MA) Patent Number: 5,479,945 Date filed: December 20, 1991 Abstract: The present invention is a removable drug delivery system used by patients suffering from lower urinary tract infections or urine disorders and disorders of the urethra and bladder. The present invention delivers antibiotics to the infected areas utilizing modified urethral plugs. It is particularly advantageous in that it maintains a therapeutic effect without risking contamination. The device includes of a balloon at the proximal end and a fluid receiving port at the distal end. The balloon is inflated by injecting fluid into the fluid receiving port and deflated by pulling on a deflation string. Excerpt(s): The present invention is a novel urethral plug which can be used as a medicine delivery system by patients suffering from lower urinary tract infections or other urine disorders and disorders of the urethra and bladder. The lower urinary tract is subject to a variety of bacterial illnesses and other disorders, which can be further characterized as renal, urethral, bladder, urethral and urinary. For example, bacteria infections of the lower urinary tract are very common, and after infancy occur about ten times more often in women than in men. The main route of infections in women ascends from the vagina through the urethra to the bladder. The majority of urinary tract infections (UTIs) are caused by gram negative bacteria such as Escherichia coli (up to 85% of UTIs), Klebsiella sp., Proteus sp., Enterobacter (Aerobacter) aerogenes, and Pseudomonas aeruginosa. Occasionally gram positive pathogens may be involved, including Staphylococcus epidermis (albus), and Staphylococcus aureus. The most common UTI is bacteriuria, or the proliferation of bacteria within the urine; as many as

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10% of adolescent girls have this condition, often in asymptomatic form. The condition is considered deserving of treatment at bacterial counts above 100,000 per ml, and acute at counts above 500,000 per ml or more. Bacteriuria may lead to, or stem from, infections of the urethra and/or bladder. Most such conditions involve urea-splitting bacteria which render the urine alkaline and favor the formation of calcified deposits and urinary stones, which in turn harbor and protect the proliferating bacteria. Infections involving bacteria in the urine and/or in the superficial regions of the urethral and bladder tissues should be highly amenable to treatment by the release of antibiotics into the urine in the bladder, or onto the walls of the urethra. The present invention comprises the delivery of antibiotics to the infected areas utilizing modified urethral plugs. Web site: http://www.delphion.com/details?pn=US05479945__ •

Method and composition for treating urinary tract infections Inventor(s): Griffith; Donald P. (4425 Hazelton, Houston, TX 77035), Musher; Daniel M. (4903 Heatherglen, Houston, TX 77035) Assignee(s): none reported Patent Number: 4,024,256 Date filed: September 18, 1975 Abstract: A method for the treatment of urinary tract infections and a composition for use in such method, such method comprising administering to a patient suffering from a urinary tract infection an effective anti-bacterial dosage of a composition comprising in combination:A. a source of methenamine, e.g. methenamine; andB. a source of hydroxamate groups, e.g., acetohydroxamic acid.The source of hydroxamate groups is administered in the amount effective to potentiate the anti-bacterial effect of the source of methenamine. The method is specifically applied to the treatment of urinary infections caused by urease producing bacteria, especially bacteria of the species proteus.In addition, where colonization of the bacteria can be tolerated and where it is only necessary to eliminate the pathogenicity of the urease producing bacteria induced infection, effective treatment can be achieved by administration of only the source of hydroxamate groups, preferably acetohydroxamic acid. Also, by maintaining the urine at an acid pH in the presence of urease producing bacteria by administering a source of hydroxamate groups, struvite and apatite urinary stones normally associated with urease producing bacteria can be dissolved. Excerpt(s): This invention relates to a method for treating urinary tract infections and a composition for use in such method; and more specifically the present invention relates to such method and composition for the treatment of urinary tract infections, specifically urinary tract infections caused by bacteria that produce urease, especially those of the species Proteus, wherein the anti-bacterial effect of methenamine is potentiated or synergized by administering a source of methenamine in combination with a source of hydroxamate groups. In addition, this invention relates to a method of eliminating the pathogenicity of urease producing bacteria by administering to a patient suffering from an infection caused by urease producing bacteria a source of hydroxamate groups. Furthermore, the present invention provides a method of dissolving struvite and apatite urinary stones generally associated with urease producing bacteria by administering a source of hydroxamate groups which provides urine of physiological pH, which due to under-saturation with respect to struvite and apatite crystals can effectively dissolve the associated stones. The increasing awareness

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of the importance of urinary tract infections has brought about the realization that adequate drug therapy is required for the treatment of the infection. With this awareness for the need for adequate drug therapy, a corresponding awareness has developed that such adequate drug therapy is difficult to provide. For example, patients with urinary tract infections often have an associated condition of stasis, stone or obstruction in the urinary tract and the chronicity or recurrence of the urinary tract infections renders unlikely successful treatment. Where such conditions exist and where the infection reoccurs, antibiotics often lose their effect due to the rapid development or acquisition of resistant mutant organisms. Still further, when a patient has a urinary stone, while the infection might be satisfactorily treated initially with a conventional antiobiotic, the stone contains viable bacteria which serve as a source for reinfection. Accordingly, while conventional antibiotics may provide short time relief from urinary tract infections complete cure freuently cannot be achieved through the administration of the conventional antibiotic agent. However, with synthetic antibacterial agents, the development of resistance is much less common. Web site: http://www.delphion.com/details?pn=US04024256__ •

Method for treating the urinary bladder and associated structures using hyaluronic acid Inventor(s): Alkemade; Stanley J. (Seaforth, CA), Morales; Alvaro (Kingston, CA) Assignee(s): Bioniche Inc. (CA) Patent Number: 5,591,724 Date filed: February 14, 1995 Abstract: A method of treating interstitial cystitis comprising contacting the internal bladder and associated structures in a mammal having interstitial cystitis with a solution containing hyaluronic acid having a molecular weight of not less than approximately 2.times.10.sup.5 Daltons in a concentration effective to treat the interstitial cystitis. Excerpt(s): The present invention relates to a novel method for treating the internal bladder and associated structures in a mammal comprising the step of contacting the internal bladder and associated structures in the mammal with a solution containing hyaluronic acid having a molecular weight of not less than approximately 2.times.10.sup.5 Daltons. More particularly, the present invention relates to a novel method for treating the internal bladder and associated structures in a mammal having interstitial cystitis comprising the step of contacting the internal bladder and associated structures in the mammal having interstitial cystitis with a solution containing hyaluronic acid having a molecular weight of not less than approximately 2.times.10.sup.5 Daltons in a concentration effective to treat the interstitial cystitis. In mammals, the unique tight junctions of bladder surface epithelial cells are the fundamental mechanism by which the bladder maintains its impermeability. However, the glycosaminoglycan layer on the luminal surface of the bladder wall may be an important defense mechanism for protecting the transitional epithelium from urinary irritants (Chelsky, M. et al. 1994. Journal of Urology, 151:346.). This glycosaminoglycan layer consists of mucopolysaccharides attached to a core protein that, in turn, is bound to a central hyaluronic acid string. This highly viscous, highly hydrophilic glycosaminoglycan layer protects the transitional epithelium of the bladder from irritants in the urine including, but not limited to, pathogens, microcrystals, proteins, calcium and carcinogens (Nickel, J. C. et al. 1993. Journal of Urology, 149:716). This

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glycosaminoglycan layer also prevents small, uncharged molecules such as urea from diffusing to and across the transitional epithelium. Thus, the glycosaminoglycan layer lining the bladder acts as a barrier between the environment within the lumen of the bladder, and the transitional epithelium of the bladder and protects this transitional epithelium from inflammation, infection, trauma, stone formation and carcinogenesis. Interstitial cystitis is a poorly understood bladder condition for which there is no universal effective treatment program (Fleischmann, J. D. et al. 1991. Journal of Urology, 146:1235). Symptoms include urgency for urination, increased frequency of urination and suprapubic pain usually relieved by voiding. Other symptoms include arthritis, spastic colon and low grade fever. Individuals with interstitial cystitis can be significantly disabled, and individuals with advanced interstitial cystitis can require major surgery in order to function. Although the etiology of interstitial cystitis remains unexplained, it has been suggested that abnormalities of or deficiencies in the glycosaminoglycan layer lining the transitional epithelium of the bladder may be a primary defect. (Eldrup J. 1983. British Journal of Urology. 55:488). These abnormalities or deficiencies may enable increased permeability of the transitional epithelium (Parsons, E. L. et al. 1990. Journal of Urology, 143:690) and this increased permeability may enable urinary solutes to gain access to the subepithelial tissue and to induce an irritative, inflammatory response that contributes to the symptoms of interstitial cystitis. Therefore, as interstitial cystitis may be related to an abnormality or deficiency in the glycosaminoglycan layer lining the transitional epithelium of the bladder, temporary replacement of this defective glycosaminoglycan layer with a defined glycosaminoglycan that protects the transitional epithelium may be effective in the treatment of interstitial cystitis. Web site: http://www.delphion.com/details?pn=US05591724__ •

Method of reducing cyclophosphamide induced hemorrhagic cystitis Inventor(s): Gordon; Donovan E. (Highland Park, IL), Rice; Deborah (Broadview, IL), Safron; Joseph A. (Grayslake, IL), White; Randy D. (Crystal Lake, IL) Assignee(s): Free Radical Sciences (Cambridge, MA) Patent Number: 5,447,712 Date filed: December 9, 1993 Abstract: A method is provided for reducing side effects caused by chemotherapeutic agents by administering to a patient in need thereof a therapeutically effective amount of a composition including L-2-oxothiazolidine-4-carboxylate specifically for reducing hemorrhagic cystitis in a patient at risk of same. Excerpt(s): The present invention relates generally to the treatment of patients using chemotherapy agents. More specifically, the present invention relates to reducing or preventing side effects caused by chemotherapeutic agents. Cancer can develop in any tissue of any organ at any age. Many cancers detected at an early stage are potentially curable. The principal objectives of cancer screening and early diagnosis are: (1) to decrease cancer mortality; (2) to lead to less radical therapy; and (3) to reduce financial costs. Merck Manual, 16th Edition, 1263, 1269 (1992). Successful therapy must be focused on the primary tumor and its metastases, whether clinically apparent or microscopic. Thus, local and regional therapy, surgery, or radiation must be integrated with systemic therapy (e.g. drugs). Id. at 1275. Web site: http://www.delphion.com/details?pn=US05447712__

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Method of treating hyperactive voiding with calcium channel blockers Inventor(s): Steers; William D. (Charlottesville, VA), Tuttle; Jeremy B. (Earlysville, VA) Assignee(s): UVA Patent Foundation (Charlottesville, VA) Patent Number: 5,698,549 Date filed: June 7, 1995 Abstract: The instant invention discloses a method of treating hyperactive voiding associated with excessive nerve growth factor production and nerve growth in patients by administering a Ca.sup.++ channel blocker. The Ca.sup.++ channel blockers verapamil and diltiazem can be administered systemically to treat hyperactive voiding, such as is associated with benign prostatic hyperplasia and interstitial cystitis. Excerpt(s): The invention relates to the use of Ca.sup.++ -channel blockers is disclosed to inhibit the production of NGF and nerve growth. Additionally, the isolation of markers in urine to indicate the presence of irritative and/or obstructive conditions in the bladder. Historically, there has been a progression from anatomical to functional studies for the diagnosis of upper and lower urinary tract obstruction. However, these studies fail to predict ultimate changes in bladder or kidney function. For example, with obstruction of the lower urinary tract, urodynamic studies often do not correlate with the severity of symptoms and fail to demonstrate capacity for return to normal function following relief of obstruction. Two major classes of voiding disorder in males and females are benign prostatic hyperplasia (BPH) and interstitial cystitis (IC). These cause, respectively, irritative/obstructive symptomology and idiopathic bladder and pelvic pain with voiding. An accumulating body of information links these conditions to changes in bladder innervation and that these may be orchestrated by neurotrophic factors. Web site: http://www.delphion.com/details?pn=US05698549__

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Method of treatment for interestitial cystitis Inventor(s): Sherman; Fred P. (Hollywood, FL) Assignee(s): Baker Cummins Pharmaceuticals, Inc. (Miami, FL) Patent Number: 4,877,791 Date filed: November 1, 1988 Abstract: A method of treating patients suffering from interstitial cystitis comprises daily administration to such patients of from about 1 to about 50 mg of the narcotic antagonists nalmefene or naltrexone. The nalmefene or naltrexone may be administered in equally divided doses from one to four times daily, preferably by the oral route. Parenteral administration may be utilized where suitable. Excerpt(s): Histopathalogic examination of bladder biopsy specimens in patients with suspected interstitial cystitis is often used to rule out other diseases (e.g., carcinoma). Typical histopathalogic findings in interstitial cystitis include a non-specific inflammatory reaction, edema and vasodilatation in the submucosa, with or without detrusor fibrosis depending on the stage of the disease. A significant increase in the number of mast cells in the bladder lining, mainly in the detrusor muscle layer, is evident, and the histamine content of the bladder wall is significantly increased. See, e.g., E. M. Meares, Urology (Supplement), vol. 29, pp. 46-48 (1987 ); W. L. Lynes et al., J. Urology, vol. 138pp. 746-52 (1987); and J. Kastrup et al., Brit. J. Urology, vol. 55, pp. 495-

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500 (1983). Recent studies indicate that the type of mast cells present in inflammatory bladder conditions such as interstitial cystitis may be of a special type know as mucosal mast cells, which are differentiated morphologically and histochemically from mast cells found, for example, in connective tissue. See J. Cornish et al., Int. Archs. Allergy Appl. Immun., vol. 81 , pp. 337-42 (1986). The progressive effects of interstitial cystitis on patients are severe and debilitating. Urinary frequency, urgency and pain, among other classic symptoms, impact dramatically and adversely on the patients' quality of life and drive them to seek any possible treatment to alleviate this disorder. Web site: http://www.delphion.com/details?pn=US04877791__ •

Methods and compositions for diagnosis and treatment of interstitial cystitis Inventor(s): Domingue; Gerald J. (3540 Rue Michelle, New Orleans, LA 70131) Assignee(s): none reported Patent Number: 5,672,517 Date filed: May 12, 1995 Abstract: The present inventor discloses a description of the preparation of ICAPs for use in diagnosis, methods of prevention and prophylaxis of interstitial cystitis. The forms can be cultivated in high concentrations of serum, they can be visualized in a light microscope, they have a characteristic morphology in an electron microscope, and they are immunogenic and antigenic. Excerpt(s): Interstitial cystitis (IC) is a chronic debilitating inflammatory disorder of the bladder. The disease is most common in women ranging in age from about thirty to sixty with onset of the condition typically occurring at about forty years of age. The most prevalent symptoms include severe abdominal pain and urinary urgency two or three times per hour, day and night. Quality of life scores in the most severe patients are lower than in chronic renal disease patients. The initiating causes are unknown and there is no cure known. The condition is categorized as "interstitial cystitis" because it is believed the disease does not affect the surface of the bladder but instead involves the spaces between the cells, namely the interstices, in the lining of the bladder. It has been suggested that IC may be an autoimmune disease. See Fall et al., J. Urol., 137:35, (1987), for example. Autoimmune diseases have been the subject of widespread attention because of the considerable morbidity worldwide that they cause. Autoimmune diseases include rheumatoid arthritis, type-1 diabetes mellitus (insulin dependent), multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, experimental allergic encephalomyelitis (EAE), to name a few. In most cases, it is believed that autoimmune diseases result from abnormal cells of the immune system destroying target tissues, either by direct killing or by producing autoantibodies. Current treatment for these diseases remains on an empirical level and is based on causing generalized immunosuppression, either with steroids or other immunosuppressive drugs. This therapeutic approach is also fraught with other problems including associated severe side effects. Further, they serve only to retard the natural progression of these autoimmune diseases. Effective therapeutic treatment, to say nothing of a cure, is beyond present day medical technology. The aberrations in the immune system resulting in these various autoimmune diseases are not well understood, despite the extensive research that has taken place in this field. See Ratliff et al. (1995) Clin. Immunol. Immunopath. 74: 209-216., for example. Web site: http://www.delphion.com/details?pn=US05672517__

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Methods of treating interstitial cystitis and urethral syndrome Inventor(s): Fleischmann; Jonathan D. (Cleveland Heights, OH) Assignee(s): Case Western Reserve University (Cleveland, OH) Patent Number: 5,145,859 Date filed: March 20, 1991 Abstract: According to the invention there is provided various methods of treating mammalian interstitial cystitis and/or urethral syndrome through the use of Nifedipine, a calcium channel antagonist which has been primarily used for the treatment of coronary artery spasms and hypertension. Specifically, the invention is directed to the adminstration of an therapeutically effective amount of Nifedipine to mammals suffering from interstitial cystitis and/or urethral syndrome. The Nifedipine may be administered in admixture with a pharmaceutically acceptable carrier in a unit dosage form. The route of administration is that deemed preferred by the attending physician, with oral administration being preferred. Excerpt(s): The present invention is directed to methods of treating mammalian interstitial cystitis and/or urethral syndrome, two painful lower urinary tract disorders for which there is no adequate treatment currently available. The methods generally comprise the administration of a pharmaceutically effective amount of Nifedipine (C.sub.17 H.sub.18 N.sub.2 O.sub.3), a calcium channel antagonist which has been primarily used for the treatment of coronary artery disease and hypertension. Since Nifedipine provides effective relief with few side effects and is an oral medication that is well tolerated and relatively inexpensive, it is an attractive therapeutic agent for the treatment of these two painful voiding disorders. More particularly, interstitial cystitial cystitis is a painful disease of the urinary bladder which is of unknown etiology and is most commonly seen in adult women. It is characterized by a number of urinary difficulties such as suprapubic pressure and pain with bladder filling, urinary frequency, nocturia, dysuria, urgency and irritative voiding asociated with morphological and histological changes in the bladder. Urethral syndrome is a related painful voiding disorder of unknown etiology effecting women exhibiting many of the conditions set forth above. In this regard, while there are many similarities between the characteristics and conditions of these two voiding disorders, they exhibit a number of different characteristics. Specifically, interstitial cystitis is a condition consisting of a symptom complex with a specific voiding pattern (frequency, urgency, nocturia, lower abdomino-perineal pain and possibly dysuria), associated with glomerulations in response to bladder filling and, if present, a Hunner's ulcer. In contrast, patients with the urethral syndrome experience dysuria, urgency (usually with frequency) and sometimes abdominoperineal pain in the absence of nocturia and the cystoscopic findings consistent with interstitial cystitis. Web site: http://www.delphion.com/details?pn=US05145859__

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Methods of treating or preventing interstitial cystitis Inventor(s): Iyengar; Smriti (Carmel, IN), Muhlhauser; Mark A. (Indianapolis, IN), Thor; Karl B. (Morrisville, NC) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 6,025,379 Date filed: August 25, 1998

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Abstract: This invention provides methods for the treatment or prevention of interstitial cystitis or urethral syndrome in a mammal which comprise administering to a mammal in need thereof an effective amount of a substituted benzimidazole, or a pharmaceutically acceptable salt or solvate thereof. Excerpt(s): Tachykinins are a family of peptides which share a common amidated carboxy terminal sequence. Substance P was the first peptide of this family to be isolated, although its purification and the determination of its primary sequence did not occur until the early 1970's. Between 1983 and 1984 several groups reported the isolation of two novel mammalian tachykinins, now termed neurokinin A (also known as substance K, neuromedin L, and neurokinin.alpha.), and neurokinin B (also known as neuromedin K and neurokinin.beta.). See, J. E. Maggio, Peptides 6 (Supplement 3):237243 (1985) for a review of these discoveries. Tachykinins are widely distributed in both the central and peripheral nervous systems, are released from nerves, and exert a variety of biological actions, which, in most cases, depend upon activation of specific receptors expressed on the membrane of target cells. Tachykinins are also produced by a number of non-neural tissues. Web site: http://www.delphion.com/details?pn=US06025379__ •

Pharmaceutical composition comprising an aqueous extract of a mixture of anemarrhena rhizoma and phellodedron bark for analgesic and anti-inflammation Inventor(s): Chung; Young-Shin (Seoul, KR), Han; Young-Bok (Seoul, KR), Hong; EunKyung (Seoul, KR), Kim; Sung-Jin (Seoul, KR), Lee; Kyung-Yung (Seoul, KR), Shin; Young-Lok (Seoul, KR) Assignee(s): Medvill Co., Ltd. (Seoul, KR) Patent Number: 6,193,977 Date filed: March 14, 2000 Abstract: The present invention is directed to a pharmaceutical composition comprising an extract of a mixture of Anemarrhena Rhizoma, a member of the family Liliaceae and, Phellodendron bark, a member of the family Rutaceae that produces analgesic and antiinflammatory effects, and its preparing method. The present invention is applicable to act on inflammation and pain, for example, chronic gastritis, arthralgia, benign prostate hyperplasia, chronic and recurrent cystitis, cervical disc, degenerative joint arthritis, rheumatoid arthritis, tennis elbow, osteoportotic pain, migraine, diabetic neuropathy pain, right flank pain, etc. The present invention a crude extract suitable for long-period administration with less side effects. Also, the present invention does not lead to dependency or resistance. Excerpt(s): The present invention relates generally to a pharmaceutical composition comprising aqueous extracts of Anemarrhena Rhizoma, a member of the family Liliaceae, and Phellodendron Bark, a member of the family Lilium for analgesic and anti-inflammation, and its preparing method. More particularly, it relates to a pharmaceutical composition comprising mixed aqueous extracts of Anemarrhena Rhizoma and Phellodendron Bark for analgesic and anti-inflammation against chronic gastritis, arthralgia, benign prostate hyperplasia, chronic and recurrent cystitis, cervical disc, degenerative joint arthritis, rheumatoid arthritis, tennis elbow, osteoportotic pain, migraine, diabetic neuropathy pain, Rt. flank pain, etc. There are two types of pain, one of which is fast pain sensed immediately in response to stimulants and the other is slow pain sensed gradually. The slow pain results from injuries to both the skin and the

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internal tissue and lasts long, while the fast pain results from injuries to the skin rather than to the internal tissue. The pain is sensed through receptors distributed over the skin and tissue, especially, those for mechanical, thermal and chemical stimulants. Upon receipt of stimulation, the receptors transmit sensation to the central nerve system. Examples of the chemicals exciting the chemical type of pain receptors include bradykinin, potassium ions, acids, proteolytic enzymes, etc. Compared to the other types of sensation, the lasting pain becomes more sensitive to stimulants and develops intolerance even to a weak stimulant. In the body system, neurons of the brain and the vertebral column secrete those substances such as morphine that elicit an analgesic effect, and regulate the pain. Examples of the analgesic substances include endorphin, enkephalin and dynorphin secreted from the brain, and serotonin and enkephalin from the vertebral column. Web site: http://www.delphion.com/details?pn=US06193977__ •

Therapeutic drug for the treatment of micturition disorders Inventor(s): Ueda; Tomohiro (Kyoto, JP), Yamauchi; Tamio (Suita, JP) Assignee(s): Taiho Pharmaceutical Co., Ltd. (Tokyo, JP) Patent Number: 6,329,428 Date filed: July 5, 2000 Abstract: The present invention is drawn to a therapeutic drug for micturition disorders and diseases of the lower urinary tract system, containing an organic acid salt of [2-[4-(3ethoxy-2-hydroxypropoxy)phenylcarbamoyl]ethyl]-dimethylsulfonium. The invention enables treatment of diseases of the lower urinary tract system which cause urinary disorders, such as interstitial cystitis and prostatitis, which arise from unelucidated causes and thus are regarded intractable diseases. Excerpt(s): The present invention relates to a therapeutic drug for treating diseases of the lower urinary tract system, including those of the bladder and prostate, which can cause micturition disorders. The invention also relates to a therapeutic drug for micturition disorders accompanying these diseases. Micturition disorder is a term which collectively refers to micturition-related pathological conditions, encompassing dysuria, pollakiuria, miction pain, and urinary incontinence. Dysuria generally refers to a state where smooth urination is disturbed. Typical symptoms include: delay between the desire to void and the initiation of micturition; thin stream of urine, time for voiding prolonged; post-micturition dribble; conscious exertion of abdominal pressure needed to initiate voiding; and sense of residual urine remaining in the bladder immediately after urination. A special form of dysuria is urinary retention, which refers to a state in which voluntary micturition is disturbed and is characterized by retention of urine. Causes of urinary retention are broadly divided into (1) those attributed to neurological factors, including incoordination of the bladder smooth muscle and detrusor-sphincter dyssynergia, and (2) those attributed to organic factors, such as prostate-associated diseases, bladder neck sclerosis, and urethral stricture. Until today, however, the causes have not yet clearly elucidated and current theory holds that neurological changes and organic changes are closely related to each other. Thus, in order to formulate a remedy, studies should be directed not only at localized anatomy, but at the entire urinary system, including the bladder, the prostate, and the external sphincter (see Medicine Journal, vol. 33, S-1, 193-197 (1997). Web site: http://www.delphion.com/details?pn=US06329428__

Patents 189

•

Treatment of cystitis-like symptoms administration of a challenge solution

with

chondroitin

sulfate

following

Inventor(s): Hahn; Sungtack Samuel (Scarborough, CA) Assignee(s): Stellar International Inc. (London, CA) Patent Number: 6,083,933 Date filed: April 19, 1999 Abstract: Cystitis of the bladder and urinary tract, particularly interstitial cystitis, are treated using effective unit doses of chondroitin sulfate. Further, cystitis patients are screened for their response to a given cystitis treatment using a method in which patients are first challenged with an irritant and then treated with a selected cystitis therapeutic. Candidates for further treatment are identified as those patients who on receiving the selected therapeutic, report relief from at least one symptom elicited with the irritant. Also provided are kits comprising solutions for carrying out this screening method. Excerpt(s): The invention relates to therapeutic and diagnostic methods useful in the treatment and assessment of cystitis, including interstitial cystitis, and related bladder conditions. Interstitial cystitis is a bladder condition associated with discomfort and pain elicited by urinary irritants, causing urgency for, and increased frequency of, urination. Because its cause is poorly understood, the development of useful treatments has followed approaches that are largely empirical and even haphazard, and these approaches have failed to yield more than a few useful therapeutic agents and treatments. As described by Sant and La Rock in Interstitial Cystitis, Vol. 21 (1), February 1994 at p.73, current therapies include pharmacotherapy, with intravesical use of dimethyl sulfoxide being the only therapy approved by the FDA. Still, a variety of other agents are in use to treat symptoms of interstitial cystitis, either alone or in combination with DMSO. Such agents include sodium oxychlorosene (Clorpactin), heparin, hyaluronic acid, steroid, sodium bicarbonate, silver nitrate, sodium pentosanpolysulfate, cromolyn sodium, lidocaine and doxorubicin. Many of these agents can be delivered orally, but to be effective are most typically delivered by instillation either as monotherapy, combination therapy or sequential therapy. These agents and therapies target the bladder mucosal lining, and provide symptomatic relief of pain, frequency and urgency. Of these therapies, however, few offer relief over sustained periods. There is a need to provide, on a cost-effective basis, agents and therapies that are useful to treat cystitis, including interstitial cystitis and related conditions of the bladder and urinary tract that result from an eroded mucosal lining. There is also a need to provide methods by which patients can be screened to reveal therapeutic agents effective to treat that patient's particular condition. It is accordingly an object of the present invention to provide such a diagnostic screening method. Web site: http://www.delphion.com/details?pn=US06083933__ •

Urethral catheter capable of preventing urinary tract infection and process for producing the same Inventor(s): Sakamoto; Izumi (Kyoto, JP), Takagi; Kunihiko (Kyoto, JP) Assignee(s): Unitika Ltd. (Amagasaki, JP) Patent Number: 4,539,234 Date filed: May 27, 1982

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Abstract: A urethral catheter composed of olefin polymer, diene polymer or silicone polymer as a base material wherein an antimicrobial substance being chemically bonded with the inside wall and/or the outside wall thereof, and a process for producing the same. This urethral catheter effectively prevents urinary tract infection for a long period of time. Excerpt(s): The present invention relates to a urethral catheter capable of preventing urinary tract infection and a process for producing the same. In many cases of spinal injury, cerebral hemorrhage and softening of the brain, after an operation the patient develops symptoms such as dysuria or urinary incontinence. In such cases, urethral catheterization using a catheter is adopted in order to secure a smooth urinary passage. This is done in order to maintain kidney functions or prevent or promote the leakage of urine. The catheters used in such cases are called urethral catheters. Such catheters must have sufficient flexibility, elasticity and innoxious property because of their use. Almost all of them are composed of a material such as an olefin polymer, diene polymer or silicone polymer as the base material. Since catheterization is a remarkably useful curative means for carrying out rapid urination, it is frequently used in fields other than urology such as surgery, internal medicine and obstetrics and gynecology. However, the procedure is defective in that the occurrence of infection is nearly unavoidable if the urethral catheter is inserted into the urinary tract. Since the urethral catheter is left in the urinary tract for a long time, microbes intrude into the urinary tract through the catheter frequently causing symptoms such as urethritis, cystitis or pyelitis. It has been reported that performing an opening continuation catheterization which is frequently used hitherto (a method of collecting urine in a container such as a glass bottle which is not sterilized), infection occurs within 3 days in 42 to 80% of the clinical test and the infection is observed in all cases after the 7th day. Web site: http://www.delphion.com/details?pn=US04539234__ •

Vaccine composition for immunization against urinary tract infection caused by E. coli Inventor(s): Brinton, Jr.; Charles C. (Pittsburgh, PA), Fusco; Peter C. (Pittsburgh, PA) Assignee(s): Bactex, Inc. (Pittsburgh) Patent Number: 4,725,435 Date filed: June 18, 1986 Abstract: There is provided a vaccine material capable of providing substantial levels of protection against urinary tract infection caused by Escherichia coli. The protecting means comprises pili of organisms having pili of the same pilic family as those on the infecting organism. Protection is given by administering the pili to the subject to be protected. Excerpt(s): Escherichia coil is a ubiquitous pathogen of man and animals causing a wide variety of diseases of clinical and economic importance. E. coli is the most frequent cause of urinary tract infections (UTI) causing the symptoms of acute and chronic cystitis, pyelonephritis, and asymptomatic bacteriuria (ABU). A general approach to this problem is disclosed in U.S. Pat. Nos. 4,454,116 and 4,454,117 to Brinton. It has been found that UTI infections are caused by E. coli organisms carrying pili belonging to three pilic families, namely, Type 1, P and p (See Race & Sanger, Blood Groups in Man, 6th. Ed., 1975, Blackwell, Oxford; Naiki & Kato, Vox Sanguinis, 37, 30, 1979). In particular, it has been found that the majority of infections are caused by organisms

Patents 191

having one or more pili belonging to at least one of seven pilic groups within the Type 1 family, four pilic groups within the P family and two pilic groups within the p family. The important designating factor in the design of the vaccines of the present invention is not the identity of the organism giving rise to the particular protecting pili. Thus, the designation of the strains giving rise to these pili is merely a matter of identifying convenience and should in no way be considered as limiting the invention to pili specifically derived from the named strains. It is considered that the present invention extends to pili derived from any strains which generate pili which fall within the above named Type 1, P and p families and furthermore, will generate antibodies which would cross react with or agglutinate the pili derived from the above named strains. Web site: http://www.delphion.com/details?pn=US04725435__

Patent Applications on Cystitis As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to cystitis: •

Antiproliferative factor Inventor(s): Hise, Michael K.; (Columbia, MD), Keay, Susan K.; (Ellicott City, MD), Kleinberg, Michael; (Baltimore, MD), Warren, John W.; (Baltimore, MD) Correspondence: David L. Marks; University OF Maryland; Baltimore Office OF Research & DEV.; 515 West Lombard Street, Suite 500; Baltimore; MD; 21201-1602; US Patent Application Number: 20020016443 Date filed: April 21, 2001 Abstract: The invention relates to a novel antiproliferative factor (APF) present in urine of patients with interstitial cystitis (IC). APF is useful as a marker for disease activity and its antagonists are useful as therapeutic medicaments for IC and other conditions associated with elevated APF. APF and its agonists are useful in the treatment of diseases associated with cell proliferation, such as bladder cancer. Excerpt(s): This application is a CIP of U.S. patent application Ser. No. 09/307,686 filed on May 10, 1999, now abandoned. U.S. Pat. No. 09/307,686 is a Divisional of U.S. Pat. No. 5,962,645 issued on Oct. 5, 1999 and filed on Oct. 3, 1997 as U.S. patent application Ser. No. 08/944,202 which claims priority to U.S. patent application Ser. No. 60/027,646 filed on Oct. 4, 1996 (now abandoned). This application claims priority to U.S. patent application Ser. No. 09/307,686, U.S. Pat. No. 5,962,645, and U.S. patent application Ser. No. 60/027,646. This application also claims priority to and is related to U.S. patent application 60/218,272 filed on Jul. 13, 2000 and to U.S. patent application Ser. No. 60/232,911 filed on Sep. 15, 2000. The invention relates to a novel antiproliferation factor found in subjects with interstitial cystitis; to methods for isolating the antiproliferation factor; to methods for using the antiproliferation factor in the treatment of conditions characterized by cellular proliferation; and to methods for diagnosing and treating interstitial cystitis. Art relating to the background of the invention is reviewed in the ensuing sections.

10

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

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

Catecholamine pharmaceutical compositions and methods Inventor(s): Dillon, Patrick F.; (East Lansing, MI), Root-Bernstein, Robert S.; (East Lansing, MI) Correspondence: Harness, Dickey & Pierce, P.L.C.; P.O. Box 828; Bloomfield Hills; MI; 48303; US Patent Application Number: 20030216413 Date filed: March 28, 2003 Abstract: Pharmaceutical compositions and method using adrenergic compounds and complement compounds. Compositions are provided comprising:(c) a subefficacious amount of an adrenergic compound; and(d) a safe and effective amount of a complement to the adrenergic compound.Methods are also provided comprising the administration of:(c) a low dose of an adrenergic compound; and(d) a safe and effective amount of a complement to said adrenergic compound.Preferably, the adrenergic compound is a catecholamine. Complements include ascorbates, opioids, polycarboxylic acid chelaters, and mixtures thereof. Preferred complements include ascorbates, particularly ascorbic acid. Methods include the treatment of neurological disorders, hypotension, forward failure, backward failure, congestive heart failure, shock, hypertension, hemorrhage, disorders associated with anesthesia, chronic obstructive pulmonary disease, asthma, colic, Crohn's disease, anaphylaxis, interstitial cystitis, overactive bladder syndrome, premature labor, myethsenia gravis, and glaucoma. Excerpt(s): This application is a continuation-in-part of International Application PCT/US01/30272, with an international filing date of Sep. 27, 2001, published in English under PCT Article 21(2), which claims the benefit of U.S. Provisional Application No. 60/236,751, filed Sep. 29, 2000. This invention relates to novel methods of treating disorders mediated by adrenergic receptors, and novel pharmaceutical compositions containing catecholamines or other adrenergic compounds. For example, the compositions and methods of this invention comprise the use of catecholamines and ascorbates in the treatment of a variety of disorders, including asthma, hypertension, and congestive heart failure. Catecholamines and related adrenergic (sympathomimetic) drugs are involved in the regulation of a wide variety of body functions. Such compounds have their effect directly or indirectly on the alpha- and beta-adrenergic receptors found in tissues throughout the body. Because the functions that are mediated by these receptors are diverse, agents that agonize or antagonize their activity are useful in the treatment of a variety of clinical disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Combination therapy for premenstrual symptoms Inventor(s): Berruti, Alessandra; (London, CA), Kapoor, Rakesh; (Saskatoon, CA) Correspondence: Alice O. Carroll, ESQ.; Hamilton, Brook, Smith & REYNOLDS,P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20020068100 Date filed: October 11, 2001

Patents 193

Abstract: Disclosed is a composition comprising ingredients a-f: a) n-6 fatty acid; b) n-3 fatty acid; c) vitamin E; d) extract of Viburnum opulus bark; e) extract of Vitex agnus castus berry; and f) bioflavonoid(s). Also disclosed is a method of treating premenstrual symptoms in a subject in need of such treatment and a method of treating irritable bowel syndrome or interstitial cystitis in a subject in need of such treatment. The method comprises the step of administering to the subject a therapeutically effective amount of the ingredients a-f, described above. Preferably, the subject is administered a composition comprising ingredients a-f. Excerpt(s): This applications claims the benefit of U.S. Provisional Application 60/239,790, filed Oct. 12, 2000, the entire teachings of which are incorporated herein by reference. Premenstrual syndrome (PMS) is a recurrent cyclic disorder associated with the cyclic hormonal rhythms of the menstrual cycle (Clin. Obstet. Gynecol. 40:564 (1997)). A large number of symptoms have been associated with PMS that are divided into physical, behavioral, and emotional symptoms. PMS may be associated with dysmenorrhea and other menstrual irregularities. Physical symptoms include bloating, abdominal and back cramps and discomfort, change in appetite, weight gain, breast tenderness and pain, and headache. Behavioral changes include anxiety, depression, lethargy, hypersomnia or insomnia, moodiness, irritability, anger, and social withdrawal. These symptoms vary in intensity from mild to severe and affect up to 90% of the women. About 5% of North American women suffer from moderate to severe symptoms affecting their daily life activities. Pharmacologically active agents have been used to treat PMS and include antidepressants of the group belonging to selective serotonin reuptake inhibitors (SSRI's), anti-inflammatory agents including non-steroidal anti-inflammatory agents, anxiolytics, hormones (progesterone), dopamine agonists, and diuretics. However, drug treatments can have many disadvantages including sideeffects and cost, and are not always effective. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition and method for treating non-bacterial cystitis Inventor(s): Katske, Floyd A.; (Los Angeles, CA) Correspondence: Robert J. Schaap, ESQ.; Suite 188; 21241 Ventura Boulevard; Woodland Hills; CA; 91364; US Patent Application Number: 20010051191 Date filed: May 2, 2001 Abstract: A composition and a method for treatment of urinary tract dysfunction and, particularly, non-bacterial cystitis and, even more particularly, non-bacterial chronic interstitial cystitis. The composition primarily relies upon the use of a bioflavonoid and, particularly, that bioflavonoid known as quercetin. The quercetin is mixed with a proteolytic digestive enzyme protease, such as bromelin and papain, as the primary active ingredients. However, the composition may optionally and beneficially include other cystitis affecting agents, such as cranberry, as well as some other active and nonactive ingredients. Excerpt(s): This application is based on and obtains the benefit of my now abandoned U.S. provisional patent application Ser. No. 60/203,486, filed May 9, 2000, for "Composition for Treating Non-Bacterial Cystitis". The invention primarily relates to a composition and method for the treatment of non-bacterial cystitis and, more particularly, to a composition and method for treating non-bacterial chronic interstitial

194 Cystitis

cystitis syndromes using bioflavonoids in a treatment composition and in a treatment method. Interstitial cystitis represents a non-specific group of urinary tract and, particularly, bladder related problems and is often characterized by pain, which may actually adopt the form of phantom symptomatic pain. Interstitial cystitis is generally a pervasive inflammatory condition of the bladder and can be disabling to a sufferer. The symptoms usually suffered are bladder pain and frequent micturition (urination). Interstitial cystitis is one of the conditions in which very few of the available therapies are effective. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compounds and methods for the treatment of urogenital disorders Inventor(s): Grayson, Stephen; (San Rafael, CA), Mak, Vivien H.W.; (Palo Alto, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020198136 Date filed: March 6, 2002 Abstract: The present invention provides methods for treating a variety of urogenital disorders, such as, for example, vaginismus, dyspareunia, vulvodynia (including vulvar vestibulitis), interstitial cystitis, nonspecific urethriris (i.e., nonspecific pain and/or burning of the urinary tract) and sexual dysfunctions, such as, for example, female sexual arousal disorders and female sexual orgasmic disorders, using a variety of compounds, including, but not limited to, NO donors, calcium channel blockers, cholinergic modulators,.alpha.-adrenergic receptor antagonists,.beta.-adrenergic receptor agonists, phosphodiesterase inhibitors, cAMP-dependent protein kinase activators (e.g., cAMP mimetics), superoxide scavengers, potassium channel activators, estrogen-like compounds, testosterone-like compounds, benzodiazepines, adrenergic nerve inhibitors, antidiarrheal agents, HMG-CoA reductase inhibitors, smooth muscle relaxants, adenosine receptor modulators, adenylyl cyclase activators, endothelin receptor antagonists, bisphosphonates and cGMP-dependent protein kinase activators (e.g., cGMP mimetics). Excerpt(s): The present application claims priority to U.S. Provisional Pat. Application Nos. 60/273,901, filed Mar. 6, 2001, and 60/334,903, filed Oct. 24, 2001, the teachings of both of which are incorporated herein by reference for all purposes. Urogenital disorders affect a large number of women and can have profound effects on life quality. Although a number of treatments are available for some of the most serious gynecological and urinary tract diseases, many urogenital disorders are still poorly understood. As a consequence, treatments are often nonexistent, inefficient and/or invasive. One example of a relatively rare, yet highly debilitating, urogenital disorder is vaginismus. Vaginismus results from the involuntary spasm of the pelvic muscles surrounding the outer third of the vagina, and interferes with a woman's ability to have a sexual relationship. This disorder is a major cause of unconsummated marriage, and can result in marked distress, interpersonal difficulty, and infertility. In addition, women suffering from vaginismus are sometimes unable to undergo a routine gynecological exam. Typical treatments of vaginismus include, for example, psychological therapy, Kegel exercises, and the use of a plastic dilator to progressively stretch the contracted muscles of the vagina. Although often effective, these treatments are time-consuming and cause high levels of anxiety.

Patents 195

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

Detection and treatment of breast disease Inventor(s): Dyster, Lyn M.; (Lewiston, NY), Frustaci, Jana M.; (Williamsville, NY), Papsidero, Lawrence D.; (Orchard Park, NY) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20020076710 Date filed: April 13, 2001 Abstract: An isolated chemokine is disclosed. The isolated chemokine is expressed preferentially in breast tissue or can be detected in breast milk. It includes from about 100 to about 132 amino acids, has a deduced molecular weight of from about 10 to about 16 kDa, and has a deduced isoionic point of from about pH 10.1 to about pH 10.7. Antibodies and binding portions thereof recognizing the subject chemokine and peptides which include the antigenic portions of the subject chemokines are described. DNA molecules which encode the subject chemokines as well as nucleic acid molecules which, under stringent conditions, hybridize to nucleic acid molecules encoding the subject chemokines or to a complement thereof are also disclosed. The chemokines, peptides, antibodies and binding portions thereof, and nucleic acid molecules can be used to detect and treat breast disease, such as inflammations, infections, mastitis, benign cystitis, benign hyperplasias, cancer and other malignancies as well as other pathological states of the mammary gland. Excerpt(s): This application is a divisional application of U.S. patent application Ser. No. 09/146,580, filed Sep. 3, 1998, which claims the benefit of U.S. Provisional Patent Application Serial No. 60/071,899, filed Jan. 20, 1998, and U.S. Provisional Patent Application Serial no. 60/092,155, filed Jul. 9, 1998, which are hereby incorporated by reference. The present invention relates to the detection and treatment of breast disease. Breast cancer is one of the largest classes of malignant disease in women. However, breast cancer presents inherent difficulties in regard to the ease with which it is detected and diagnosed. This is in contrast to detection of some other common cancers, including skin and cervical cancers, the latter of which is based on cytomorphologic screening techniques. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Method for alleviating syndromes and conditions of discomfort of the mammalian intestinal and genito-urinary tracts Inventor(s): Finnegan, Sarah; (Mays Landing, NJ), Kligerman, Alan E.; (Egg Harbor Township, NJ) Correspondence: Akin, Gump, Strauss, Hauer & Feld, L.L.P.; One Commerce Square; 2005 Market Street, Suite 2200; Philadelphia; PA; 19103; US Patent Application Number: 20020099037 Date filed: January 17, 2002 Abstract: Glycerophosphates, particularly calcium glycerophosphate (CGP), have been found to mitigate certain abdominal-area physical problems including irritable bowel syndrome and urinary urgency. It is believed that calcium and glycerophosphate, taken

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orally, are introduced into the human and other animal system such that the glycerophosphate and/or calcium exert a damping, soothing, irritant-interdictive or antispasmodic action on the intestinal, urinary bladder and other smooth muscle organs. Using glycerophosphates, a method is provided for alleviating, palliating, and reducing the syndromes and conditions of discomfort resulting from a variety of diseases, including irritable bowel syndrome, interstitial cystitis, inflammatory bowel disease, fibromyalgia, urinary urgency, benign prostatic hypertrophy, vulvodynia and external genital pain. It is also suggested that muscular energy supplied via glycolysis, the source of anaerobic energy, may be facilitated by the administration of a glycerophosphate moiety to the body's glycerophosphate shuttle. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/262,759, filed Jan. 19, 2001. Inflammatory Bowel Syndrome (IBS) is an ailment of the intestines which is characterized by high motility of the small and large intestines to a degree that may be characterized as `spasms`. These muscular spasms do not always move smoothly, in concert, or even in the same direction; sometimes the peristaltic motions are adverse to one another, causing intestinal bulging in the area between them. There is almost always pain and cramping involved, which may be accompanied by diarrhea or constipation. These effects have been likened to those associated with severe lactose intolerance (Merck Manual of Diagnosis and Therapy On-Line, "Differential Diagnosis," p.5, Sep. 29, 2000). The spasms are not the same as the normal non-peristaltic movements of colonic smooth muscle, called halustrations, which appear to have the purpose of maximizing contact of the colonic contents with the lining of the colon walls, thus promoting absorption of nutrients. Rather, sufferers of IBS have the perception of pain and cramping as well as constipation and/or diarrhea. There have also been reports that acidic foods make the symptoms of IBS worse or may even "trigger" this ailment. IBS has no apparent etiology; that is, it does not readily disclose any particular physical clue as to what causes it. The Merck Manual (Sep. 30, 2000) explains that the cause of irritable bowel syndrome is unknown and that no anatomic cause has been found. The unknown cause has also been expressed in the online publication of the U.S. Government's NIDDK National Digestive Diseases Information Clearinghouse. Furthermore, the publication, Best and Taylor's Physiological Basis of Medical Practice, 12.sup.th Edition, explains that IBS is probably not a single nosological entity and thus is difficult to describe in physiological or anatomical terms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHODS AND MEANS OF DETECTING NITRIC OXIDE SYNTHASE Inventor(s): SESSA, WILLIAM C.; (MADISON, CT), SMITH, SHANNON D.; (GUILFORD, CT), WEISS, ROBERT M.; (NORTH HAVEN, CT), WHEELER, MARCIA A.; (BRANFORD, CT) Correspondence: Jane Massey Licata; Law Offices OF Jane Massey Licata; 66 E Main Street; Marlton; NJ; 08053 Patent Application Number: 20020164658 Date filed: September 14, 1998 Abstract: Methods for identifying and monitoring increased or decreased levels of inducible nitric oxide synthase in biological samples are provided. A collection device for detecting inducible nitric oxide synthase in biological samples is also provided. Detection of inducible nitric oxide synthase is useful in the diagnosis of inflammatory

Patents 197

responses such as infections mediated by bacteria, yeast or viruses, transplant rejection, rheumatoid arthritis, interstitial cystitis and cancer. Excerpt(s): The present invention provides methods and means for identifying and monitoring increased or decreased levels of inducible nitric oxide synthase in biological samples. Nitric oxide synthase activity is elevated in the inflammatory response resulting from several diseases or conditions, including, but not limited to, bacterial infections including urogenital tract infections and bacterially related sepsis, organ transplant rejection and cancer. Nitric oxide synthase activity is decreased in urine of patients with interstitial cystitis. One of the most common bacterial infections in humans is that of the urinary tract. Patients who need rapid diagnosis of urinary tract infections (UTIs) include premature newborn infants, prepubertal girls and young boys, sexually active women, elderly males and females, pre-operative patients, patients with chronic disease, patients with neurological disorders, patients with genitourinary congenital disorders including urethral valves and reflux, patients with sickle cell disease, patients with renal disease and polycystic kidney disease, patients having undergone renal transplantation and pregnant patients. The diagnosis of UTI in the elderly and in infants, in particular, is difficult because of different signs and symptoms and the inability to communicate, respectively. Failure to diagnose UTIs can lead to urosepsis, emphysematous cystitis and scarring. Accordingly, there is a need for a rapid, cost effective, sensitive test for UTI. While a definitive diagnosis of urinary tract infections can be obtained by microbial culturing, this test is costly and results from the culture can take up to 48 hours to obtain. Newer technologies involving bacterial antibodies offer no clear advantages over culturing techniques. Studies have confirmed a direct relationship between urine nitrite and urinary tract infections. Accordingly, the Griess reagent which detects nitrite is commonly employed in a dipstick to screen urine for microorganisms. Leukocyte esterase dipstick tests are also used routinely for the rapid diagnosis of urinary tract infections (UTIs). However, these tests have been found to have different sensitivities and specificities for patients with different clinical manifestations. For example, Lachs et al. reported that this dipstick test for urinary tract infection was highly sensitive in patients with a high prior probability of infection but insensitive in patients with a low prior probability of infection (Lachs et al., Ann. Intern. Med. 1992, 117:135-40). Accordingly, as taught by Dr. Martin F. Shapiro in the commentary to this study, the dipstick test for urinary tract infection lacks sensitivity precisely in those patients for whom an effective diagnostic test would be most useful; patients with vague symptoms for whom the diagnosis is not clear. It has been estimated that the current dipstick technologies detect only approximately 50% of UTIs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treating bladder disorders Inventor(s): Hedley, Mary Lynne; (Lexington, MA) Correspondence: Janis K. Fraser, PH.D.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020193332 Date filed: February 12, 2002 Abstract: Methods of treating bladder disorders, including bladder cancer and inflammatory bladder diseases such as interstitial cystitis are disclosed. The methods include identifying a mammal that has or is at risk for having a bladder disorder and administering isolated nucleic acid sequences to the mammal. Nucleic acids used in the

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methods of the invention contain unmethylated CpG sequences, which are thought to modulate the immune response. Also included are methods that use nucleic acids encoding alpha-MSH. The nucleic acid sequences may be administered individually or together or can be included in the same nucleic acid. Excerpt(s): This application claims priority from U.S. Provisional Application No. 60/268,175, filed Feb. 12, 2001, the entire content of which is incorporated herein by reference. The invention relates to methods of treating bladder disorders. Specifically, the methods can be used to treat disorders such as bladder cancer and inflammatory bladder diseases such as interstitial cystitis. Bladder disorders, including bladder cancer and bladder inflammatory disorders, are on the rise. Bladder cancer is the most common urologic malignancy and was predicted to affect approximately 54,000 people in 1998 (de Vere White & Stapp (1998) Oncology (Huntingt) 12:1717-26). Current treatments include local resection, use of intravesical agents and radical cystectomy (Whittlestone & Persad (2000) Hosp Med 5:336-40). Bladder cancer is the fourth most commonly diagnosed malignancy in men and the eighth most common in women and represents a wide spectrum of disease, ranging from superficial, well-differentiated disease to highly malignant tumors (Metts et al. (2000) J. Matl. Med. Assoc. 92: 285-94). Primary radical surgery remains the standard of care for invasive bladder cancer (Kim & Steinberg (2000) J. Urol. 164(3 Pt 1): 627-32). Transurethral resection (TUR) of the superficial transitional cell carcinoma (TCC) of the bladder is known to be insufficient in controlling the disease because of the unacceptable rates of recurrence, progression and ultimate cystectomy. Adjuvant intravesical chemo-and/or immunotherapy is administered in an effort to enhance the efficacy of surgery alone (Melekos & Moutzouris (2000) Curr Pharm Des 3:345-59). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pelvic disorder treatment device Inventor(s): Cohen, Ehud; (Ganei Tikva, IL), Gross, Yossi; (Moshav Mazor, IL), Nissenkorn, Israel; (Ramat Aviv, IL) Correspondence: Ladas & Parry; 26 West 61st Street; New York; NY; 10023; US Patent Application Number: 20030100930 Date filed: November 29, 2001 Abstract: A device for treating a medical condition is provided, and a surgical procedure for implanting the device is disclosed. The device includes a sensor, which is adapted to generate a signal responsive to a state of a patient, and at least one electrode, which is adapted to be coupled to a pelvic site of the patient. A control unit is adapted to receive the signal, to analyze the signal so as to distinguish between an imminent stress incontinence event and an imminent urge event, and, responsive to analyzing the signal, to apply an electrical waveform to the at least one electrode. In various configurations, the device may be used alternatively or additionally to treat fecal incontinence, interstitial cystitis, chronic pelvic pain, or urine retention. Excerpt(s): The present invention relates generally to electronic medical devices, and specifically to devices to relieve problems associated with urinary incontinence and other pelvic disorders. Urinary incontinence affects millions of people, causing discomfort and embarrassment, sometimes to the point of social isolation. In the United States, recent studies have shown that as many as 25 million persons, of whom approximately 85% are women, are affected by bladder control problems. Incontinence

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occurs in children and young adults, but the largest number affected are the elderly. Urethral hypermobility--Weakness of or injury to pelvic floor muscles causes the bladder to descend during abdominal straining or pressure, allowing urine to leak out of the bladder. This is the more common source of stress incontinence. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Screening process for atopic dermatitis Inventor(s): Chan, Edward K L; (Gainesville, FL), Muro, Yoshinao; (Showa-ku, JP), Ochs, Robert L; (Pittsburg, PA), Tan, Eng M; (La Jolla, CA) Correspondence: The Scripps Research Institute; Office OF Patent Counsel, Tpc-8; 10550 North Torrey Pines Road; LA Jolla; CA; 92037; US Patent Application Number: 20030215875 Date filed: April 24, 2003 Excerpt(s): The field of this invention is diagnosis of atopic dermatitis. Atopic dermatitis (AD) is a chronic, relapsing, pruritic skin disorder that generally first appears in childhood and frequently progresses to asthma and/or allergic rhinitis in the adult (Hanifin et al., Acta Dermatovener (Stockholm) Suppl 1980; 92:44-47; Leung et al., Dermatology in General Medicine, 4th edition, 1993, pp. 1543-1564; Cooper, J Invest Dermatol 1994; 102:128-137). There are no reliable laboratory markers for this condition but AD patients often have elevated serum IgE levels, allergic reactivity to foods and to other common allergens such as pollens, molds, and insects. There have also been reports of antinuclear antibodies (ANAs) in this condition (Taniguchi et al., Acta Derm Venereol (Stockh) Suppl 1992; 176:62-64; Tada et al., Dermatol 1994; 189:38-40). The prevalence of AD appears to be on the rise, with 10-15% of the population being affected at some time during childhood (Beltrani, J Allergy Clin Immunol 1999; 104:587-598; Leung, J Allergy Clin Immunol 1999; 104: S99-S108). We now report the finding of an autoantibody-autoantigen system in 30% of patients with AD which is also shared to a lesser extent by patients with asthma and interstitial cystitis (IC). IC is a urinary bladder condition in which the classical pathology is characterized by predominant mononuclear cell infiltration of the lamina propria with lymphocytes, plasma cells and mast cells (Gillenwater, et al., J Urol 1988; 140:203-206). The present invention provides a process of screening patients for atopic dermatitis. The process includes the step of determining, in sera of the patient, the presence of antibodies against nuclear antigens such as transcription co-activator p75, wherein the presence of such antibodies indicates atopic dermatitis. The screening process can be used to detect atopic dermatitis in patients suffering from other conditions such as asthma or interstitial cystitis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Synthetic peptide composition as immunogens for prevention of urinary tract infection Inventor(s): Wang, Chang Yi; (Cold Spring Harbor, NY) Correspondence: Morgan & Finnegan L.L.P; Maria C.H. Lin; 345 Park Avenue; New York; NY; 10154-0053; US Patent Application Number: 20030027979 Date filed: December 22, 2000

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Abstract: The invention provides a peptide immunogen comprising a FAFSD target peptide or an anlogue thereof, covalently linked to a helper T cell epitope and optionally to an invasin immunostimulatory domain. The present invention also provides for the use of such peptide immunogens to elicit the production in mammals of high titer polyclonal antibodies, which are specific to the FAFSD target peptide. The peptide immunogens are expected to be useful in evoking antibodies that prevent the adherence of E. coli and other enterobacteria to the bladder mucosa for protection against urinary tract infection. Excerpt(s): This invention relates to peptide compositions that are useful as immunogens for the prevention of urinary tract infection. The peptide immunogen of the present invention comprises a FimH Adhesin Functional Site-Derived (FAFSD) target peptide and a helper T cell epitope (Th) having multiple class II MHC binding motifs. Optionally, the immunogenic peptide further comprises an invasin domain, which acts as a general immune stimulator. The helper T cell epitope and the invasin domain enable the host to generate an immune response specific against the FAFSD target peptide to prevent the adherence of Escherichia coli and other enterobacteria to the bladder mucosa and confer protection against urinary tract infection. Urinary tract infection (UTI) is one of the most common disorders in women and children, resulting in 7-8 million physician and hospital visits per year at a cost of over $1 billion. It is estimated that by age 30, roughly 50 percent of women have had at least one incidence of UTI with 2-10 percent having recurrent UTI. Females are generally more prone to UTI because of their anatomy. Recent studies have shown that, on average, women who are 18-40 years old suffer 1-2 infections over a two year period. Older women are at risk with the incidence being as high as 30%. In most cases, UTI is not life threatening. Standard antibiotics usually offer quick relief, but when left untreated, the chronic recurrence of urinary tract infection can cause kidney damage and even death. A vaccine would reduce this toll but there has been little success in the development of a practicable vaccine for UTI (Service, Science 1997, 276:533). Earlier attempts to produce a UTI vaccine using whole fimbriae were not successful in protecting against a broad range of disease-causing bacteria. Intact whole fimbriae do not elicit a strong antibody response to FimH adhesin. (Hanson and Brinton, Nature 1988, 332:265; Johnson, 1991; U.S. Pat. No. 4,454,117, Langermann et al, 1997). Vaccines comprising peptides of the major fimbrial protein FimA have been reported (Schmidt et al, J Exp Med, 1985; 161:705; U.S. Pat. No. 4,740,585). However, antibodies raised against FimA are not antiadhesive and do not block attachment. Furthermore, vaccines based on the major components of the fimbriae contain variable sites and are expected to provide a narrow typespecific protection (Abraham et al, 1988). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of interstitial cystitis Inventor(s): Hise, Michael; (Columbia, MD), Keay, Susan; (Ellicott City, MD), Warren, John; (Baltimore, MD) Correspondence: Intellectual Property/technology Law; P.O. Box 14329; Research Triangle Park; NC; 27709; US Patent Application Number: 20010000783 Date filed: December 20, 2000 Abstract: Interstitial cystitis (IC) is a chronic bladder disease for which the exact etiology is unknown and for which there is no reliably effective treatment. However, it is known

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that the bladder epithelium is often abnormal in IC. We discovered that human bladder epithelial cells from both normal controls and IC patients are inhibited from proliferating by an anti-proliferative factor (APF) present in IC urine specimens. Inhibited proliferation may cause epithelial abnormalities characteristic of IC such as ulcerations and multiple tears in the bladder epithelium. We further discovered that 1) levels of heparin binding--epidermal growth factor-like growth factor (HB-EGF), a factor known be important for epithelial cell proliferation and wound healing in other tissues, are abnormally low in the urine of patients suffering from IC as compared to asymptomatic controls or patients with acute bacterial cystitis; 2) the APF found in IC urine specimens inhibits HB-EGF production by bladder epithelial cells; and 3) that the administration of rHB-EGF blocks the effects of APF on bladder epithelial cells from either IC patients or controls. The invention herein is directed to the administration of HB-EGF, or a functional derivative or agonist thereof, to bladder epithelial cells to inhibit the effects of APF on bladder cell proliferation, thereby reducing or eliminating the chronic damage to the bladder epithelium. HB-EGF or a functional derivative may be used as a therapy for patients suffering from IC or other diseases characterized by inhibited epithelial cell proliferation. Excerpt(s): 2. The development of the present invention was supported by the University of Maryland, Baltimore, Md., the Fishbein Foundation, and the Interstitial Cystitis Association. 3. The field of this invention generally relates to the treatment of diseases characterized by bladder epithelial abnormalities using heparin-binding epidermal growth factor-like growth factor (HB-EGF) or a functional derivative thereof to stimulate epithelial cell proliferation. The field of this invention specifically relates to the treatment of Interstitial Cystitis (IC) using recombinant HB-EGF to overcome the inhibition of bladder epithelial cell proliferation caused by a low molecular weight antiproliferative factor found in the urine of IC patients. 4. Interstitial cystitis (IC) is a chronic inflammatory disease of the bladder for which the etiology is unknown. IC often has a rapid onset with pain, urgency and frequency of urination, and cystoscopic abnormalities including petechial hemorrhages (glomerulations) or ulcers that extend into the lamina propria (Hunner's ulcers).sup.1,2. The rapid onset of IC is followed by a chronic course with partial remissions and re-exacerbations, which can continue for up to 30 years.sup.1,2. As a result of the absence of a specific cause for and lack of understanding of its pathogenesis, there is currently no generally accepted treatment proven to be reliably efficacious. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

TREATMENT OF INTERSTITIAL CYSTITIS USING TOPICAL APPLICATION OF MENTHOL AND L-ARGININE Inventor(s): Thompson, Ronald J.; (Ft. Thomas, KY) Correspondence: Donald N. Halgren; 35 Central Street; Manchester; MA; 01944; US Patent Application Number: 20030065032 Date filed: October 1, 2001 Abstract: A topical treatment for interstitial cystitis in the urinary tract of a mammal comprising an ointment including a component of L-Arginine in a carrier base compound. The ointment may also include a component of menthol. The concentration of menthol and of L-Arginine is each preferably limited to five percent.

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Excerpt(s): This invention relates to a method to utilize a topical preparation of menthol and L-arginine as a therapeutic modality for interstitial cystitis, which is otherwise known as "overactive bladder". The function of the urinary bladder is to accumulate a significant volume of urine before the sensation of bladder fullness, and the need to urinate, is perceived. This is a bodily function most of us take for granted. The normal volume of urine before bladder fullness is appreciated is 300 to 400 cc. Frequency is a patient-reported symptom of frequent urination. In the absence of either excessive fluid intake or the therapeutic use of diuretics, urination should be necessary only every 4 to 6 hours. Cystitis is an inflammation of the bladder commonly caused by a bacterial infection in the urine and the superficial bladder wall. Symptoms associated with cystitis are frequent urination (frequency), pelvic pressure, dysuria (painful urination) and nocturia (the need to urinate that interrupts normal sleep). The diagnosis of bacterial cystitis is established by the identification of the presence of white blood cells upon microscopic examination of the urine. Effective treatment of a bacterial cystitis is accomplished with oral antibiotics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

URINARY INCONTINENCE THERAPY Inventor(s): AGERSBORG, HELMER P. K.; (BLUE BELL, PA), CRUZ, FRANCISCO; (PORTO, PT) Correspondence: Greenlee Winner And Sullivan P C; 5370 Manhattan Circle; Suite 201; Boulder; CO; 80303; US Patent Application Number: 20010006982 Date filed: August 21, 1998 Abstract: The invention includes a method of treating neurogenic urinary dysfunction that comprises contacting urinary bladder mucosa of a patient afflicted with neurogenic urinary dysfunction with an effective dose of a homovanilloid compound, in particular a compound selected from the group RTX, TYX, 20-homovanillyl-mezerein or 20homovanillyl-12-deoxyphorbol-13-- phenylacetate. The invention includes treatment of urge incontinence due to detrusor hyperreflexia (DH). The invention also includes treatment of sensory hypersensitivity of the bladder resulting from prostate hypertrophy or interstial cystitis, as well as other neurogenic conditions resulting in increased micturition frequency or decreased bladder capacity, with or without frank incontinence. Excerpt(s): Priority is claimed from U.S. Provisional Application 60/057,385 filed Aug. 28, 1997. Certain homovanilloid compounds, notably the homovanillyl diterpene esters resiniferatoxin (RTX) and tinyatoxin (TYX) are known to have physiological effects similar to capsaicin (CAP). Depending on which physiological response is measured, the homovanilloids are more potent than CAP, on a molar basis, by a factor of 10-10,000. In particular, RTX, TYX and other homovanilloids have been shown to be effective for desensitizing sensory nerves in a manner similar to CAP but at lower dosage (U.S. Pat. Nos. 4,939,149 and 5,021,450, incorporated herein by reference). Urinary incontinence, the inability to maintain voluntary control of micturition, is a condition affecting millions of men and women. The control of micturition is a complex physiological process including neural reflex pathways, some with and some without central nervous system control, smooth and voluntary muscles and hormonal effects. (See review by DeGroat, [1997] Urology 50[Supplement 6A]:36-52.) A large subset of urinary incontinence is at least partly neurogenic. The clinical term "overactive bladder" is used

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generally to denote any form of incontinence characterized by increased frequency of micturition or desire to void, whether complete or episodic, and where loss of voluntary control ranges from partial to total. "Urge incontinence" is the involuntary loss of urine associated with an abrupt and powerful desire to void. Urge incontinence is usually, but not always, associated with the urodynamic finding of involuntary (uninhibited) contractions of the detrusor muscle. The detrusor muscle provides the primary force in expelling urine from the bladder. A large subset of patients with uninhibited detrusor have some sort of neurologic impairment, in which case the clinical term is "detrusor hyperreflexia" (DH). The term detrusor instability" or "unstable detrusor" is reserved for conditions where there is no neurologic abnormality. There is evidence suggesting that detrusor instability may result from subclinical neurologic disease or from primary muscle disease (Payne, C. K. [1998] Urology 51[Suppl.2A]:3-10). Common neurologic disorders associated with detrusor hyperreflexia (DH) are Parkinson's disease, stroke, diabetes, multiple sclerosis (MS), peripheral neuropathy and spinal cord injury. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of pentosan polysulfate to treat certain conditions of the prostate Inventor(s): Striker, Gary E.; (Miami, FL) Correspondence: Baker Norton Pharmaceuticals, INC.; 4400 Biscayne Boulevard; Miami; FL; 33137; US Patent Application Number: 20020010140 Date filed: January 19, 2001 Abstract: The invention relates to the field of pharmacology. More particularly, the invention relates to the treatment of prostate conditions, such as BPH. The invention provides new therapeutic compositions and methods for treating BPH, as well as chronic prostatitis, prostadynia, and irritative bladder conditions, other than interstitial cystitis. The compositions and methods according to the invention, which may be administered orally, efficaciously and safely treat the designated conditions by causing regression of established lesions and reduction of bladder irritation. In particular, the compositions and methods of the invention treat BPH by reducing the size of the prostate gland and decreasing the associated obstructive symptoms. Excerpt(s): The invention relates to the field of pharmacology. More particularly, the invention relates to the treatment of prostate conditions, such as benign prostatic hyperplasia. Benign prostatic hyperplasia (BPH) is a common disease. The advent of medical therapy for BPH has had a major impact on the practice of urologic care. Gee et al., JURL 160: 1804-1807 (1998), teaches that the overwhelming majority of American urologists use medical therapy first in patients with moderate symptoms. Currently available medical therapy includes alpha blocking agents, 5-alpha-reductase inhibitors and phytotherapeutic agents. Five-alpha-reductase inhibitors block the conversion of testosterone to dihydrotestosterone (DHT). Moore et al., Euro URL 28: 304-309 (1995) teaches that finasteride, a type II 5-alpha-reductase-inhibitor, produced a 72% decrease in DHT, prostate volume reductions of 30% and a reduction in prostate specific antigen. Boyle et al., Urology 48: 398-405 (1996) teaches that the symptomatic response to finasteride is greater in prostates weighing over 40 grams. Carraro et al., Prostate 29: 231-240 (1996) discloses that phytoestrogens provide improvements in uroflow, symptom scores and quality of life nearly equal to that provided by finasteride. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with cystitis, 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 “cystitis” (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 cystitis. You can also use this procedure to view pending patent applications concerning cystitis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON CYSTITIS Overview This chapter provides bibliographic book references relating to cystitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on cystitis 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 “cystitis” (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 cystitis: •

Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies Source: Oakland, CA: New Harbinger Publications, Inc. 2000. 236 p. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. Often misdiagnosed, people with IC are routinely put through a battery of tests, prescribed a variety of medications, or even encouraged to have surgical interventions. This book is a self care guide designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for

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delivering proper care to the IC patient. The book includes eleven chapters: an introduction that covers the basics of IC, diagnosing IC, the causes of IC, medical conditions associated with IC, oral medications, medications introduced into the bladder, the male with IC, surgery and the IC patient, sex and IC, conservative therapies for IC, and support for the IC patient. The book concludes with a glossary of terms, a list of resource organizations, a bibliography of additional readings by chapter, and a subject index. •

Overcoming Bladder Disorders: Compassionate, Authoritative Medical and Self-Help Solutions for Incontinence, Cystitis, Interstitial Cystitis, Prostate Problems, and Bladder Cancer Source: New York, NY: HarperPerennial. 1991. 338 p. Contact: Available from HarperCollins Publishers. Box 588, Dunmore, PA 18512. (800) 242-7737 or (800) 331-3861. Fax (800) 822-4090. PRICE: $12.50 plus $2.75 shipping and handling (as of 1996). ISBN: 0060920831. Summary: This guidebook provides current information on the diagnosis, treatment, and prevention of bladder disorders. Ten chapters cover taking control of bladder problems; the anatomy and physiology of the healthy bladder; incontinence; cystitis and urethritis; painful bladder syndrome, including interstitial cystitis and urethral syndrome; prostate problems; bladder cancer; strategies for enhancing sexuality; and coping strategies for everyday survival. The book also includes an index of diagnostic tests; a drug glossary; a glossary of urological terms; a reference list; and a subject index. Each chapter includes a brief list of resources for readers who wish to explore a particular topic in more depth. 18 figures. 115 references.

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Evaluating and Managing Interstitial Cystitis Source: Englewood Cliffs, NJ: University Research Associates Rx, Inc. 1997. 47 p. Contact: Available from University Research Associates Rx, Inc. 560 Sylvan Avenue, Englewood Cliffs, NJ 07632. (201) 816-0110. PRICE: Contact distributor directly for current prices for professionals. Summary: This monograph reviews current concepts of the pathogenesis of interstitial cystitis (IC) as well as new methods to successfully diagnose and manage this disease. IC is characterized by severe urinary frequency, urgency, and lower abdominal or perineal pain in the absence of any bacterial infection or other definable pathology. IC also has mild and moderate states. IC typically has a gradual onset with an insidious progression. The author notes that it may be that IC encompasses a number of different etiologies, all involving a bladder insult that ultimately results in urinary frequency and urgency. An important purpose for using this broader definition of IC is that many patients with milder forms could readily benefit from therapy if the diagnosis is considered. One of the main diagnostic problems with IC is a lack of pathologic findings that are readily identified and quantified. Diagnostic procedures discussed include the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC, the use of a voiding log, the physical examination, urodynamics, the potassium test, cystoscopic inspection and hydrodistension, and biopsy. Treatment options covered include antidepressant therapy, hydrodistension of the bladder under anesthesia, dimethyl sulfoxide (DMSO) instillation, antihistamines, steroids, intravesical silver nitrate, sodium oxychlorosene, heparinoid therapy, pentosan polysulfate (Elmiron), and surgery. The author stresses that, when discussing therapy with the patient, it is important to emphasize that if symptoms have been present for more than a year, no

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particular therapy is likely to be curative. While the patient may have a significant remission of symptoms, in all probability relapse will occur. The author concludes that perhaps 75 to 85 percent of patients with moderate to severe IC can experience significant, indefinite remissions with conservative therapy and avoid the need for extirpative surgery. The monograph concludes with the package insert information for Elmiron. 3 figures. 6 tables. 105 references. (AA-M).

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

A Taste of the Good Life: A Cookbook for an Interstitial Cystitis Diet by Beverley Laumann (1998); ISBN: 096657060X; http://www.amazon.com/exec/obidos/ASIN/096657060X/icongroupinterna

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Along the Healing Path : Recovering from Interstitial Cystitis by Catherine M. Simone; ISBN: 0966775015; http://www.amazon.com/exec/obidos/ASIN/0966775015/icongroupinterna

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Awakening Through the Tears: Interstitial Cystitis and the Mind/Body/Spirit Connection by Catherine M. Simone; ISBN: 0966775023; http://www.amazon.com/exec/obidos/ASIN/0966775023/icongroupinterna

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Conquering Cystitis by Kingsley; ISBN: 0852235763; http://www.amazon.com/exec/obidos/ASIN/0852235763/icongroupinterna

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Coping With Cystitis by Caroline Clayton (1995); ISBN: 0859697150; http://www.amazon.com/exec/obidos/ASIN/0859697150/icongroupinterna

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Cystitis by Angela Kilmartin; ISBN: 0446512036; http://www.amazon.com/exec/obidos/ASIN/0446512036/icongroupinterna

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Cystitis by Peter Evans; ISBN: 0846400537; http://www.amazon.com/exec/obidos/ASIN/0846400537/icongroupinterna

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Cystitis (Natural Way Series) by Jacqueline Young (1997); ISBN: 1852308893; http://www.amazon.com/exec/obidos/ASIN/1852308893/icongroupinterna

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Cystitis and What to Do About It; ISBN: 090365265X; http://www.amazon.com/exec/obidos/ASIN/090365265X/icongroupinterna

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Cystitis Comp Self Help Gd by Angela Kilmartin; ISBN: 0446325147; http://www.amazon.com/exec/obidos/ASIN/0446325147/icongroupinterna

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Cystitis: A Time to Heal with Yoga & Accupressure, An Eight Week Exercise Program with Special Information on Interstitial Cystitis & Urethral Syndrome by Emmey A. Ripoll, Dawn R. Mahowald (2003); ISBN: 1403388709; http://www.amazon.com/exec/obidos/ASIN/1403388709/icongroupinterna

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Cystitis: A Woman Doctor's Guide to Prevention and Treatment by Dr.Kathryn with Sue Berkman Schrotenboer; ISBN: 0356154483; http://www.amazon.com/exec/obidos/ASIN/0356154483/icongroupinterna

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Cystitis: And How to Cope with It by Peter Evans; ISBN: 0246110759; http://www.amazon.com/exec/obidos/ASIN/0246110759/icongroupinterna

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Cystitis: How to Prevent Infection and Inflammation (A Thorsons Book) by Angela Kilmartin; ISBN: 0722529961; http://www.amazon.com/exec/obidos/ASIN/0722529961/icongroupinterna

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Cystitis: The New Approach to Overcoming Your Discomfort by Caroline Shreeve; ISBN: 0722512260; http://www.amazon.com/exec/obidos/ASIN/0722512260/icongroupinterna

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Diets to Help Cystitis (Diets to Help Series) by Ralph McCutcheon; ISBN: 0722517033; http://www.amazon.com/exec/obidos/ASIN/0722517033/icongroupinterna

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Diets to Help Cystitis (Diets to Help) by Ralph McCutheon; ISBN: 0722528728; http://www.amazon.com/exec/obidos/ASIN/0722528728/icongroupinterna

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Interstitial Cystitis by Grannum R. Sant (Editor) (1997); ISBN: 0397516959; http://www.amazon.com/exec/obidos/ASIN/0397516959/icongroupinterna

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Interstitial Cystitis (1990); ISBN: 354019598X; http://www.amazon.com/exec/obidos/ASIN/354019598X/icongroupinterna

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Interstitial Cystitis by Philip M. Hanno, David R. Staskin; ISBN: 038719598X; http://www.amazon.com/exec/obidos/ASIN/038719598X/icongroupinterna

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Nature cure for cystitis by Clifford Quick; ISBN: 0722502958; http://www.amazon.com/exec/obidos/ASIN/0722502958/icongroupinterna

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Overcoming Bladder Disorders: Compassionate Authoritative Medical and Self-Help Solutions for Incontinence, Cystitis, Interstitial Cystitis, Prostate by Rebecca Chalker, Kristene E. Whitmore (Contributor); ISBN: 0060162775; http://www.amazon.com/exec/obidos/ASIN/0060162775/icongroupinterna

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Overcoming Cystitis by Wendy Smith; ISBN: 0553267132; http://www.amazon.com/exec/obidos/ASIN/0553267132/icongroupinterna

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Patient to Patient : Managing Interstitial Cystitis & Overlapping Conditions by Gaye Grissom Sandler, Andrew B. Sandler; ISBN: 0970559003; http://www.amazon.com/exec/obidos/ASIN/0970559003/icongroupinterna

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Pointers to the Common Remedies: Nephritis and Its Suppression, Renal Calculi and Renal Colic, Cystitis, Enuresis, Retention by M.L. Tyler (1981); ISBN: 0946717508; http://www.amazon.com/exec/obidos/ASIN/0946717508/icongroupinterna

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Sexual Cystitis by Kilmartin; ISBN: 0099556901; http://www.amazon.com/exec/obidos/ASIN/0099556901/icongroupinterna

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Solving the Interstitial Cystitis Puzzle: My Story of Discovery and Recovery by Amirit K. Willis (2003); ISBN: 0971086923; http://www.amazon.com/exec/obidos/ASIN/0971086923/icongroupinterna

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The Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies by Robert M. Moldwin (Illustrator); ISBN: 1572242108; http://www.amazon.com/exec/obidos/ASIN/1572242108/icongroupinterna

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The Official Patient's Sourcebook on Interstitial Cystitis by James N., Md. Parker (Editor), et al (2002); ISBN: 0597832218; http://www.amazon.com/exec/obidos/ASIN/0597832218/icongroupinterna

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Tinkle Power: A Woman's Guide to Healing Cystitis and Incontinence by Mary Brooks; ISBN: 0968325815; http://www.amazon.com/exec/obidos/ASIN/0968325815/icongroupinterna

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To Wake in Tears: Understanding Interstitial Cystitis by Catherine M. Simone (1998); ISBN: 0966775007; http://www.amazon.com/exec/obidos/ASIN/0966775007/icongroupinterna

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Understanding Cystitis by Kilmartin; ISBN: 0099367807; http://www.amazon.com/exec/obidos/ASIN/0099367807/icongroupinterna

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Understanding Thrush, Cystitis and Women's Genital Symptoms by Caroline Bradbeer; ISBN: 1903474000; http://www.amazon.com/exec/obidos/ASIN/1903474000/icongroupinterna

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Victims of Thrush and Cystitis by Angela Kilmartin; ISBN: 0099406608; http://www.amazon.com/exec/obidos/ASIN/0099406608/icongroupinterna

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Whole Woman Homeopathy: The Comprehensive Guide to Treating PMS, Menopause, Cystitis, and Other Problems - Naturally and Effectively by Judyth Reichenberg-Ullman; ISBN: 0761524118; http://www.amazon.com/exec/obidos/ASIN/0761524118/icongroupinterna

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Woman Doctor's Guide to Overcoming Cystitis by Kathryn Schrotenboer, M.D. Cox, et al; ISBN: 0451160061; http://www.amazon.com/exec/obidos/ASIN/0451160061/icongroupinterna

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You Don't Have to Live With Cystitis!/How to Avoid It--What to Do About It by Larrian Gillespie, Sandra Blakeslee; ISBN: 0892563028; http://www.amazon.com/exec/obidos/ASIN/0892563028/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “cystitis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

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An experimental study of the etiology of incrusted cystitis with alkaline urine together with a review of the relationship between proteus ammoniae and certain

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

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varieties of urinary calculi. Author: Hager, Benjamin Harry.; Year: 2001; [Minneapolis] 1927 •

Electro-therapeutist. The modern treatment of stricture, prostatitis, urethritis, cystitis, fistula and ulceration of the rectum by electrolysis and cataphoresis. Author: Smith, Elijah W.; Year: 1875; Terre Haute [1902, c1901]

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Experimental study of the etiology of incrusted cystitis with alkaline urine together with a review of the relationship between proteus ammoniae and certain varieties of urinary calculi. Author: Hager, Benjamin Harry; Year: 1927

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Pyuria; or, Pus in the urine, and its treatment. Comprising the diagnosis and treatment of acute and chronic urethritis, prostatis, cystitis, and pyelitis. Tr. by Walter B. Platt. Author: Ultzmann, Robert,; Year: 1997; New York, Appleton, 1884

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Studies in the etiology and pathology of pyelitis ureteritis and cystitis cystica. Author: Morse, Harry Dodge,; Year: 2002; [Minneapolis] 1925

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The challenge of chronicity in the treatment of urinary tract infections. Author: Nepera Chemical Co.; Year: 1901; [Yonkers, 1956?]-

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The health of women; anaemia, cystitis, backache, constipation, piles, indigestion, nerves, the change, sex in middle age. Author: Greengross, Wendy.; Year: 1928; [London] British Medical Assn. [1974?]; ISBN: 0900221968 http://www.amazon.com/exec/obidos/ASIN/0900221968/icongroupinterna

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The percentage of post-operative cystitis at the Church Home and Infirmary from August 1, 1924 to Dec. 6, 1925. Author: Wilson, H. V. P.; Year: 1904; [Baltimore, 1926]

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The treatment of cystitis Author: Kelly, Howard A. (Howard Atwood),; Year: 1975; [Toronto: s.n., 1905?]

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The woman doctor's guide to overcoming cystitis Author: Schrotenboer, Kathryn.; Year: 1987; New York: New American Library, c1987; ISBN: 0452259479 http://www.amazon.com/exec/obidos/ASIN/0452259479/icongroupinterna

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Understanding cystitis. Author: Kilmartin, Angela.; Year: 1983; London, Heinemann Health Books [1973]; ISBN: 0433184752 http://www.amazon.com/exec/obidos/ASIN/0433184752/icongroupinterna

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Urinary tract infections and the cost of antimicrobial resistance: focus on acute uncomplicated cystitis. Author: McGraw-Hill Healthcare Information Group. Healthcare Information Programs.; Year: 1905; Minneapolis, MN: Healthcare Information Programs, McGraw-Hill Healthcare Information Group, c2001

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XIV. Five cases of rupture of the urethra treated by external urethrotomy and suture. XV. A case of cyst of the kidney, apparently cured by a single aspiration. XVI. A case of cancer of the urethra. XVII. A case of scirrhous cancer of the bladder. and a case of cystitis with ulceration. XVIII. A case of sacculated bladder, with autopsy. Author: Cabot, Arthur Tracy.; Year: 1990; Boston: D. Clapp; Son, 1896

Chapters on Cystitis In order to find chapters that specifically relate to cystitis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and cystitis 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 “cystitis” (or synonyms)

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into the “For these words:” box. The following is a typical result when searching for book chapters on cystitis: •

Biology of Cystitis: Host and Bacterial Factors Source: in Coggins, C.H., ed. Annual Review of Medicine: Selected Topics in the Clinical Sciences, Volume 50. Palo Alto, CA: Annual Reviews. 1999. p. 149-158. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail: [email protected]. Website: www.AnnualReviews.org. PRICE: $60.00 plus shipping and handling. ISBN: 0824305507. Summary: Cystitis (bladder infection) is caused by a relatively small number of bacterial species. This review focuses on the biology of the urinary tract and the bacterial properties necessary to cause cystitis. The regulation of virulence factors at the different stages of the infection is considered, and a general model for the pathogenesis of urinary tract infection is proposed. The authors stress that, to colonize and grow in the urinary tract, these organisms have developed and acquired special properties (the virulence factors) that allow them to overcome the defenses of the urinary tract, particularly clearance by urine flow. These virulence factors are unlikely to be required during transmission from host to host, and sometimes their constitutive expression may actually be disadvantageous. Such factors are therefore regulated by the environment and in a coordinate manner to ensure their most appropriate expression for the conditions encountered. Although knowledge of the bacterial responses to the urinary tract environment is still in its infancy, it is clear that bacteria can monitor and regulate their gene expression to increase their chances of survival during infection and that genetic information that facilitates this survival can be transferred from strain to strain. 38 references. (AA-M).

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Diagnosis and Management of Interstitial Cystitis Source: in Carlin, B.I. and Leong, F.C., eds. Female Pelvic Health and Reconstructive Surgery. New York, NY: Marcel Dekker, Inc. 2003. p. 263-279. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $185.00 plus shipping and handling. ISBN: 0824708229. Summary: Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder that causes a constellation of irritative voiding symptoms and pelvic pain in the setting of negative urine cultures. This chapter on the diagnosis and management of interstitial cystitis (IC) is from a textbook that provides comprehensive, authoritative coverage of female pelvic health and reconstructive surgery. The author reviews historical concepts of the disease, current etiological theories and associated disorders, techniques for diagnosis, and options for management. 1 figure. 3 tables. 78 references.

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Interstitial Cystitis: Painful Bladder Syndromes Source: in Blaivas, J.G. Conquering Bladder and Prostate Problems: The Authoritative Guide for Men and Women. New York, NY: Plenum Publishing Corporation. 1998. p. 129-146. Contact: Available from Kluwer Academic-Plenum Publishing Corporation. 233 Spring Street, New York, NY 10013-1578. (800) 221-9369 or (212) 620-8035. Fax (212) 647-1898. Website: www.plenum.com. PRICE: $26.95. ISBN: 0306458640.

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Summary: Interstitial cystitis is a painful urinary disease that is characterized by marked frequency of urination and pain in the lower abdomen or vaginal area. This chapter on interstitial cystitis (IC) is from a book for people who have urinary bladder and prostate problems: people who urinate too often, who plan their daily activities around the availability of a bathroom, men with prostate problems, women with incontinence, and people with bladder pain. The book is written in a clear, nontechnical, humorous style that makes the material more accessible to the lay reader. IC is an uncommon condition that afflicts about 250,000 to 500,000 Americans, over 90 percent of whom are women. The cause is unknown. The most important aspect of the evaluation for IC is to have a proper checkup to be sure that the symptoms are not caused by a simple problem like a urinary tract infection, and to exclude more serious conditions such as bladder cancer. Treatment is empirical, and there are many different therapeutic regimens, but treatment can be successful in the majority of patients. The author discusses the role of behavior modification, oral medications, intravesical instillations of medications, and hydrodistension of the bladder as treatment options. A detailed case study is presented to show the use of behavior modification to treat IC. 1 figure. •

Interstitial Cystitis 101: The Basics Source: in Moldwin, R.M. Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies. Oakland, CA: New Harbinger Publications, Inc. 2000. p. 5-8. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. This chapter on the symptoms of IC is from a self care book designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for delivering proper care to the IC patient. IC is a disease recognized by its symptoms; there are no specific blood or urine tests that firmly tell a clinician whether IC is present or not. The physician reviews the patient's medical history, the physical exam, and other tests designed to make sure that no other disease is present that might cause identical symptoms. The average IC patient's symptoms begin between age 30 and 50 years, but IC has been reported both in early childhood and in later adult life. IC is divided into two categories: classical (ulcerative) and nonclassical (nonulcerative). The presence of typical symptoms and a bladder ulcer makes the diagnosis of IC quite simple, but patients with nonulcerative disease are seen far more often. In the nonulcerated form of the disease, no specific lesions are noted upon routine bladder inspection. There is also a wide range in the severity of disease. The author concludes with a listing of commonly reported symptoms.

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Lower Urinary Tract Infections in Women Source: in Hanno, P.M.; Malkowicz, S.B.; Wein, A.J. Clinical Manual of Urology. New York, NY: McGraw-Hill, Inc. 2001. p.173-183. 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.

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Summary: This chapter is from a handbook that serves as a basic, portable reference tool for the busy medical student and house officer rotating on the urology service and that 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. This chapter considers lower urinary tract infections (UTIs) in women. Topics include the incidence of UTIs; definition and classification; pathogenesis; patient care management, including for uncomplicated isolated (one time) cystitis (bladder infection), for unresolved bacteriuria (bacteria in the urine), and for recurrent bacterial cystitis; the choice of appropriate antibiotic for treatment; and managing asymptomatic bacteriuria in pregnant women and in elderly patients. A patient care algorithm is provided. The information in the chapter is presented in outline format, for ease of reference, and line drawings and radiographs illustrate the chapter. The chapter concludes with a list of five self-assessment questions and their answers. 1 figure. 1 table. 7 references. •

Cystitis and Urethritis Source: in Chalker, R.; Whitmore, K.E. Overcoming Bladder Disorders: Compassionate, Authoritative Medical and Self-Help Solutions for Incontinence, Cystitis, Interstitial Cystitis, Prostate Problems, and Bladder Cancer. New York, NY: HarperPerennial. 1991. p. 98-132. Contact: Available from HarperCollins Publishers. Box 588, Dunmore, PA 18512. (800) 242-7737 or (800) 331-3861. Fax (800) 822-4090. PRICE: $12.50 plus $2.75 shipping and handling (as of 1996). ISBN: 0060920831. Summary: This chapter on cystitis and urethritis is from a guidebook that provides current information on the diagnosis, treatment, and prevention of bladder disorders. The authors provide information to help readers understand how the bladder works, who may be susceptible to bladder infections and why, how bacteria get into the bladder, and how bacteria affect the bladder. They review new diagnostic guidelines that have been developed by urologists and methods of treatment that have been successful in breaking the cycle of recurrent cystitis. The authors also outline detailed self-help recommendations for women who suffer from recurrent bladder infections. The chapter concludes with a brief list of resources for readers who wish to explore this topic in more depth. The book includes an index of diagnostic tests, a drug glossary, a glossary of urological terms, a reference list, and a subject index. 26 references. (AA-M).

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Painful Bladder Syndrome: Interstitial Cystitis and Urethral Syndrome Source: in Chalker, R. and Whitmore, K.E. Overcoming Bladder Disorders: Compassionate, Authoritative Medical and Self-Help Solutions for Incontinence, Cystitis, Interstitial Cystitis, Prostate Problems, and Bladder Cancer. New York, NY: HarperPerennial. 1991. p. 133-179. Contact: Available from HarperCollins Publishers. Box 588, Dunmore, PA 18512. (800) 242-7737 or (800) 331-3861. Fax (800) 822-4090. PRICE: $12.50 plus $2.75 shipping and handling (as of 1996). ISBN: 0060920831 (paperback). Also available from National Association for Continence (NAFC). P.O. Box 8310, Spartanburg, SC 29305-8310. (800)BLADDER or (864) 579-7900. Fax (864) 579-7902. Summary: This chapter on interstitial cystitis (IC) and urethral syndrome is from a guidebook that provides up-to-date information on the diagnosis, treatment, and prevention of bladder disorders. The authors provide a self-evaluation checklist that

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notes the symptoms and typical experiences of people who have IC. They then discuss topics including the symptoms in detail; pregnancy and IC; possible causes of IC; preparing to consult a health care provider; diagnostic considerations; and the classification of IC. The authors also discuss the range of treatments that are available and review the advantages and disadvantages of each, including laser treatment, bladder instillations, drug therapy, electrical stimulation, bladder retraining, acupressure and acupuncture, self-help strategies, and surgical options. An additional section discusses the urethral syndrome. The chapter concludes with a brief list of resources for readers who wish to explore this topic in more depth. The book includes an index of diagnostic tests; a drug glossary; a glossary of urological terms; a reference list; and a subject index. 30 references. •

Cystitis and Interstitial Cystitis Source: in Crook, W.G. Yeast Connection and the Woman. Jackson, TN: Professional Books, Inc. 1995. p. 147-158. Contact: Available from Professional Books, Inc. 680 West Forest Avenue, Box 3246, Jackson, TN 38301. (901) 423-5400. Fax (901) 423-5402. PRICE: $17.95. ISBN: 0933478224. Summary: This chapter, from a book on yeast infections in women, covers cystitis and interstitial cystitis (IC). The author reprints many suggestions from self-help guides and comments from patients who have struggled through the often-lengthy process of having IC diagnosed. Topics include the use and overuse of antibiotics, symptoms, therapeutic options, including drug therapy and dietary modification, risk factors for cystitis, and the role of yeast infections in chronic cystitis, including interstitial cystitis. 4 references.

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Acute Dysuria and Urinary Tract Infections Source: in Carlson, K.J. et al. Primary Care of Women. St. Louis, MO: Mosby-Year Book, Inc. 1995. p. 126-132. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177 or (314) 872-8370. Fax (314) 432-1380. PRICE: $69.95 (as of 1995). ISBN: 0801676770. Summary: This chapter, from a medical reference for clinicians engaged in the primary care of women, discusses acute dysuria and urinary tract infections (UTI's). Topics include epidemiology; the causes of acute cystitis; the evaluation of acute dysuria, including history and physical examination, and diagnostic tests; management, including choice of therapy; and recurrent UTI's, including diagnostic tests and management options. The author dispels many myths traditionally taught about women with dysuria and proposes a scheme for categorizing the condition of women with acute dysuria. The author also presents dosage information for treating specific types of UTI's. 5 tables. 20 references.

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Urinary Tract Infections and Infection Stones Source: in Kursh, E.D., and McGuire, E.J., eds. Female Urology. Philadelphia, PA: Lippincott-Raven Publishers. 1994. p. 495-516. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. PRICE: $108.00 plus shipping. ISBN: 039751154X.

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Summary: This chapter, from a textbook on female urology, reviews urinary tract infections (UTIs) and infection stones. The first section discusses UTIs, including definitions; pathogenesis; host susceptibility; epidemiology; clinical manifestations, such as acute or chronic pyelonephritis, focal bacterial nephritis, renal abscess, pyonephrosis, xanthogranulomatous pyelonephritis, renal tuberculosis, and acute cystitis; diagnostic considerations; and treatment options for acute cystitis, recurrent cystitis, acute pyelonephritis, asymptomatic bacteriuria, and renal abscess. The latter section describes infection stones, discussing their pathogenesis, evaluation, treatment, and follow-up. 13 figures. 1 table. 79 references. •

Urinary Tract Infections in Adults Source: in Landau, L.; Kogan, B.A. 20 Common Problems in Urology. New York, NY: McGraw-Hill, Inc. 2001. p. 63-76. 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: Urinary tract infections (UTIs) continue to occupy a large proportion of the primary care clinician's practice. Primary care clinicians must maintain an interest in UTI, must understand the mechanisms that result in such infection, and need to develop a rational, therapeutic strategy that incorporates the most up to date evidence-based information available to them. This chapter on UTIs in adults is from a text on common problems in urology (written for the primary care provider). The author first offers a practical classification system for UTIs to use in general practice; this system simply divides UTIs into two categories: simple and complicated. This categorization of UTIs into uncomplicated and complicated allows the physician to develop a rational diagnostic treatment algorithm that is useful in clinical practice. The author then discusses uncomplicated UTI (simple cystitis or bladder infection, recurrent simple cystitis, and acute nonobstructive pyelonephritis, kidney infection), and complicated UTI, including acute infections, catheter-associated UTI, urinary stones (urolithiasis), pregnancy, UTI in the elderly, and prostatitis. The author covers three types of prostatitis: acute bacterial prostatitis, chronic prostatitis, and prostatodynia. A patient evaluation algorithm is also provided. The presentation, diagnosis, and treatment of simple cystitis are relatively simple and consistent. The patient is started on a short course of a first line antibiotic. It appears from the literature that 3 days of treatment is superior to single dose therapy, and in the particular case of simple cystitis, longer therapy may offer no further advantages. The antibiotics of choice for simple cystitis include the fluoroquinolones, trimethroprimsulfmathoxazole (or trimethroprim alone), or nitrofurantoin. The dose, adverse effects, and potential drug interactions should be familiar to all clinicians; regimes for uncomplicated UTIs are summarized in a table. 3 figures. 6 tables. 15 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to cystitis have been published that consolidate information across

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various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •

1998-1999 Complete Directory for People with Rare Disorders Source: Lakeville, CT: Grey House Publishing, Inc. 1998. 726 p. Contact: Available from Grey House Publishing, Inc. Pocket Knife Square, Lakeville, CT 06039. (860) 435-0868. Fax (860) 435-0867. PRICE: $190.00. ISBN: 0939300982. Summary: This directory from the National Organization for Rare Disorders (NORD) provides a wealth of information on diseases and organizations. The directory offers four sections: disease descriptions, disease specific organizations, umbrella organizations, and Government agencies. In the first section, the directory includes descriptions of 1,102 rare diseases in alphabetical order. Each entry defines the disorder, then refers readers to organizations that might be of interest. Diseases related to kidney and urologic diseases are Alport syndrome, Bartter's syndrome, blue diaper syndrome, branchiotorenal syndrome, renal cell carcinoma, citrullinemia, cystinuria, Drash syndrome, Fraser syndrome, Galloway Mowat syndrome, Golderhar syndrome, Goodpasture syndrome, benign familial hematuria, hemolytic uremic syndrome, hepatic fibrosis, IgA nephropathy, interstitial cystitis, Loken senior syndrome, medullary cystic disease, medullary sponge kidney, Mullerian aplasia, multiple myeloma, nail patella syndrome, Ochoa syndrome, Peyronie disease, polycystic kidney diseases, prostatitis, purpura, renal agenesis, renal glycosuria, WAGR syndrome, Wegener's granulomatosis, and Wilms tumor. Each of the 445 organizations listed in the second section is associated with a specific disease or group of diseases. In addition to contact information, there is a descriptive paragraph about the organization and its primary goals and program activities. Entries include materials published by the organization as well as the diseases the organization covers. The third section lists 444 organizations that are more general in nature, serving a wide range of diseases (for example, the American Liver Foundation). The final section describes 74 agencies that are important Federal Government contacts that serve the diverse needs of individuals with rare disorders. A name and keyword index concludes the volume.

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You will need to limit your search to “Directory” and “cystitis” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “cystitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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CHAPTER 7. MULTIMEDIA ON CYSTITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on cystitis. 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 cystitis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “cystitis” 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 “cystitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on cystitis: •

Cystitis: Don't Ignore Painful Urination Source: Madison, WI: University of Wisconsin Hospitals and Clinics, Department of Outreach Education. 2000. (videocassette). Contact: Available from University of Wisconsin Hospital and Clinics. Picture of Health, 702 North Blackhawk Avenue, Suite 215, Madison, WI 53705-3357. (800) 757-4354 or (608) 263-6510. Fax (608) 262-7172. PRICE: $19.95 plus shipping and handling; bulk copies available. Order number 032700R. Summary: Cystitis, or bladder infection or inflammation, is a common problem, characterized by frequency of urination, urgency to urinate, and burning upon urination. This videotape program, moderated by Carol Koby, discusses bacterial cystitis (bladder infection) and the more chronic interstitial cystitis (IC, an inflammation of the lining of the bladder). The program features nurse practitioners Sue Marten and Stacy Cesario, who identify symptoms, describe the different types of cystitis, and review medical and self care treatment options. The nurse practitioners first review the

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anatomy of the female urogenital tract and the types of symptoms that may be experienced. Although both types of cystitis are characterized by dysuria (painful urination) and urinary frequency and urgency, IC also tends to include intense abdominal pain, painful intercourse, and lack of response to antibiotic therapy. Other topics covered include the symptoms of an infection that has spread to the kidneys, risk factors for certain populations (pregnant women or women with diabetes), the causes of bacterial infections, diagnostic considerations, self help and prevention strategies, disorders associated with IC, the etiology of IC (which is largely unknown, but seems to require a previous inflammatory process), and treatment options for IC (bladder distention, chlorpactin, bladder instillation of DMSO, oral medications, and TENS, electrical stimulation). The program features interviews with some patients, who describe the difficulties of obtaining an accurate diagnosis of IC and their success with self care, diet therapy, bladder retraining, and stress reduction. The program concludes by referring viewers to the Interstitial Cystitis Association (ICA 301-610-5300). •

Bacterial Cystitis: A Clinical Update Source: Secaucus, NJ: Network for Continuing Medical Education (NCME). 1992. 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: $20 for 2-week rental or $50 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: This continuing education videotape program addresses bacterial cystitis, a common problem in women, and focuses on unexpected diagnostic and management challenges, especially in patients with recurrent urinary tract infections (UTIs). Within the context of representative hypothetical cases, Dr. F.C. Lowe provides an update on the differential diagnosis, pathogenesis, and management of bacterial cystitis. Key diagnostic challenges and appropriate therapies are covered, including the possible occurrence of false-negative dip-test readings and misinterpretations of culture colony counts. (AA-M).

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Self-Care for the Interstitial Cystitis Patient Source: Rockville, MD: Interstitial Cystitis Association. 1995. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $14.50 (as of 1995). Summary: This patient education videotape program provides viewers with guidelines for coping strategies and self-care therapies to use in managing interstitial cystitis (IC). Narrated by Dr. Kristene Whitmore, the program defines IC; describes the symptoms and the chronic nature of the disease; explains the role of the Interstitial Cystitis Association (ICA); briefly reviews the conventional treatments for IC, including drug therapy, surgery, and drugs instilled into the bladder; stresses the need for a combination of traditional and alternative therapies to reduce the frequency of IC flareups and to prolong remission of the disease; and details alternative management strategies. Strategies covered include dietary modifications, including how to perform a strict elimination diet; urine alkalization, with baking soda, potassium citrate, antacids, urine dilution, and dietary acid restriction; bladder holding protocol (a bladder muscle strengthening program, not behavior modification); the role of exercise; stress reduction techniques, including biofeedback, self hypnosis, visualization, yoga, massage therapy, and acupressure and acupuncture; helpful products, including absorbent pads, external

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catheters, and portable toilets; travel tips; support and information available from the ICA; and the role of counseling. The videotape depicts various patients using each of these strategies. •

Rational Approach to the Diagnosis, Treatment and Management of Interstitial Cystitis Source: Rockville, MD: Interstitial Cystitis Association. 1994. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $14.50 (as of 1995). Summary: This professional education videotape provides clinicians with an overview of the diagnosis, treatment, and management of interstitial cystitis (IC). Narrated by Dr. Phillip Hanno, the program defines IC; describes the symptoms and the chronic nature of the disease; discusses the exclusionary diseases to consider in the diagnosis of IC; demonstrates the urodynamic workup of a suspected IC patient, including the role of cystoscopy, bladder distension, and biopsy; details the treatment options for IC, including hydrodistension, DMSO therapy, oxychlorosene sodium (Chlorpactin) therapy, the use of tricyclic antidepressants, the use of sodium pentosanpolysulfate (Elmiron-includes availability of this not-yet-approved drug) transcutaneous electrical nerve stimulation (TENS), narcotics, fulgeration, and surgery; and outlines self-care strategies including acid restriction and urine alkalization, exercise, stress reduction, acupressure, biofeedback, products and supplies, bladder holding protocol, and patient education and support. The program concludes with a brief discussion of the role of the Interstitial Cystitis Association (ICA) in research and patient education and support.

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

Bacterial cystitis [videorecording]: a clinical update Source: Franklin C. Lowe; Year: 1992; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1992

•

Homeopathic treatment of bladder infections [sound recording]. Year: 1991; Format: Sound recording; Berkeley, CA: Conference Recording Service, [1991]

•

Management of urinary tract infections in children [slide] Source: John W. Duckett and the A. U. A., inc; Year: 1980; Format: Slide; [Baltimore]: A. U. A.; Norwich, N. Y.: for loan or sale by Norwich-Eaton Pharmaceuticals, Film Library, 1980]

•

Mrs. Fiver [electronic resource]: a lady with cystitis. Year: 1985; Format: Electronic resource; Philadelphia, PA: Lippincott, c1985

•

Urinary tract infection [slide] Source: University of Michigan, Medical Center, Kidney Foundation, Michigan Dept. of Public Health; produced by University of Michigan,

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Medical Center, Independent Study Unit; Year: 1977; Format: Slide; Ann Arbor: The University: [for loan or sale by its Medical Center Media Library], c1977

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CHAPTER 8. PERIODICALS AND NEWS ON CYSTITIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover cystitis.

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

Cefpodoxime-proxetil effective in treatment of female cystitis Source: Reuters Industry Breifing Date: March 28, 2003

•

Antibiotic overuse in cystitis could be cut with pyuria and nitrite testing Source: Reuters Industry Breifing Date: March 18, 2002

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•

Interstitial cystitis is poorly understood syndrome Source: Reuters Medical News Date: January 05, 2001

•

Antimicrobial resistance of urinary tract pathogens causing cystitis in women increasing Source: Reuters Medical News Date: February 24, 1999

•

Cystitis bacteria becoming drug resistant Source: Reuters Health eLine Date: February 23, 1999

•

Oral L-arginine efficacious for interstitial cystitis pain Source: Reuters Medical News Date: February 16, 1999

•

Antiproliferative factor a noninvasive marker for interstitial cystitis Source: Reuters Medical News Date: January 01, 1999

•

Data On Bacterial Etiology Of Interstitial Cystitis Remains Elusive Source: Reuters Medical News Date: February 10, 1998

•

Interstitial Cystitis Not Caused By Bacteria Source: Reuters Health eLine Date: February 04, 1998

•

Urine Epithelial Cell Growth Factor Levels Altered In Patients With Interstitial Cystitis Source: Reuters Medical News Date: October 16, 1997

•

Cimetidine Shows Efficacy In Treatment Of Interstitial Cystitis Symptoms Source: Reuters Medical News Date: September 09, 1996

•

Sexual Activity And Use Of Diaphragm With Spermicide Linked To Urinary Tract Infection Source: Reuters Medical News Date: August 15, 1996

•

Sex, Spermicides Cause Urinary Tract Infections Source: Reuters Health eLine Date: August 14, 1996

•

[] - Bayer Corporation Introduces New 100 Mg Cipro Tablets For Cystitis Source: Reuters Medical News Date: May 10, 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

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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 “cystitis” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “cystitis” (or synonyms). If you know the name of a company that is relevant to cystitis, 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 “cystitis” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “cystitis” (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 cystitis:

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•

Interstitial Cystitis: What Is It and What Can Be Done? Source: Quality Care. 15(2): 3. Spring 1997. Contact: Available from National Association for Continence. P.O. Box 8310, Spartanburg, SC 29305-8310. (800)-BLADDER or (864) 579-7900. Fax (864) 579-7902. Web site: http://www.nafc.org. Summary: This newsletter article provides readers with a brief overview of interstitial cystitis (IC), a painful bladder condition in which the lining and muscle wall of the bladder are inflamed. Unlike common cystitis, IC is believed NOT to be caused by bacteria and does not respond to conventional antibiotic therapy. The possible causes include bacteria or viruses yet to be identified, allergies, abnormality in immune function, an unidentified defect in the bladder lining, or hormonal factors. The symptoms of IC include urgency and frequency of urination; pain and pressure in the bladder, urethra, or vagina; and waking at night to urinate. The author describes the use of cystoscopy and bladder distension to diagnose IC and cautions that many physicians are not familiar with IC and do not know how to diagnose the condition. If symptoms are mild to moderate, treatment will begin with conservative therapies, such as dietary changes, stress reduction, and certain medications. In many cases, the same bladder overdistention procedure used to diagnose IC has been found to relieve symptoms for up to 6 months or longer for many people. Elmiron, the first oral medication to be specifically indicated for IC, was approved by the Food and Drug Administration in 1996. Elmiron helps 30 to 40 percent of the people with IC, but may take 3 to 6 months to take effect. Other treatments include DMSO instillation and a variety of painkillers, muscle relaxants, bladder analgesics, and sleep medications. The article concludes with the contact information for the Interstitial Cystitis Association (ICA). (AA-M).

•

Fibro and Interstitial Cystitis Source: Fibromyalgia Wellness Letter. 2(2): 3. April 1999. Contact: Available from Fibromyalgia Wellness Letter (Arthritis Foundation). P.O. Box 921907, Norcross, GA 30010-1907. (877) 775-0343. Summary: This newsletter article uses a question and answer format to provide people who have fibromyalgia with information on interstitial cystitis (IC). This chronic inflammatory bladder condition, which is characterized by pain in the bladder and pelvic region and is often accompanied by urinary urgency and frequency, affects about 10 percent of those who have fibromyalgia. Although the cause of IC is unknown, some evidence suggests that it may be an autoimmune disorder. Other researchers speculate that bacteria may play a role. There is no definitive test to diagnose IC, so a doctor must rule out other conditions. A urologist may then perform a cystoscopy to look for glomerulations, a stiff bladder wall, or Hunner's ulcers. Cystoscopic hydrodistension is useful for both the diagnosis and the treatment of IC. Oral medications are the least invasive treatment for IC. Medications that may help include antidepressants such as amitriptyline, antihistamines such as hydroxyzine, and pentosan polysulfate sodium. Another treatment for IC is instillation, or a bladder wash, which involves using a catheter to fill the bladder with a medicinal solution for 10 to 15 minutes. Dimethyl sulfoxide is the only drug approved for instillation, but sodium hyaluronate and bacillus Calmette-Guerin are being studied as well. Other treatment options include transcutaneous electrical stimulation, sacral nerve stimulation, and surgery.

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Academic Periodicals covering Cystitis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to cystitis. In addition to these sources, you can search for articles covering cystitis 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 9. 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 cystitis. 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 nonprofit 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 cystitis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to cystitis: Atropine, Hyoscyamine, Methenamine, Methylene Blue, Phenyl Salicylate, and Benzoic Acid •

Systemic - U.S. Brands: Atrosept; Dolsed; Hexalol; Prosed/DS; UAA; Urimed; Urised; Uriseptic; Uritab; Uritin; Uro-Ves http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202075.html

Caffeine •

Systemic - U.S. Brands: Cafcit; Caffedrine Caplets; Dexitac Stay Alert Stimulant; Enerjets; Keep Alert; Maximum Strength SnapBack Stimulant Powders; NoDoz Maximum Strength Caplets; Pep-Back; Quick Pep; Ultra Pep-Back; Vivarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html

Cinoxacin •

Systemic - U.S. Brands: Cinobac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202141.html

Dimethyl Sulfoxide •

Mucosal - U.S. Brands: Rimso-50 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202196.html

Doxycycline •

Dental - U.S. Brands: Atridox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203716.html

Doxycycline for Dental Use •

Systemic - U.S. Brands: Periostat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203724.html

Fluoroquinolones •

Systemic - U.S. Brands: Avelox; Cipro; Cipro I.V.; Floxin; Floxin I.V.; Levaquin; Maxaquin; Noroxin; Penetrex; Tequin; Zagam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202656.html

Fosfomycin •

Systemic - U.S. Brands: Monurol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203522.html

Loracarbef •

Systemic - U.S. Brands: Lorabid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202680.html

Mesna •

Systemic - U.S. Brands: MESNEX http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202352.html

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Methenamine •

Systemic - U.S. Brands: Hiprex; Mandelamine; Urex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202354.html

Nitrofurantoin •

Systemic - U.S. Brands: Furadantin; Macrobid; Macrodantin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202414.html

Pentosan •

Systemic - U.S. Brands: Elmiron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203359.html

Phosphates •

Systemic - U.S. Brands: K-Phos M. F.; K-Phos Neutral; K-Phos No. 2; K-Phos Original; Neutra-Phos; Neutra-Phos-K; Uro-KP-Neutral http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202463.html

Sulfonamides and Trimethoprim •

Systemic - U.S. Brands: Bactrim; Bactrim DS; Bactrim I.V.; Bactrim Pediatric; Cofatrim Forte; Cotrim; Cotrim DS; Cotrim Pediatric; Septra; Septra DS; Septra Grape Suspension; Septra I.V.; Septra Suspension; Sulfatrim; Sulfatrim Pediatric; Sulfatrim S/S; Sulfatrim Suspension; S http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202781.html

Trimethoprim •

Systemic - U.S. Brands: Proloprim; Trimpex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202579.html

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

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

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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.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to cystitis by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “cystitis” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for cystitis: •

Nifedipine http://www.rarediseases.org/nord/search/nodd_full?code=224

•

Pentosan polysulphate sodium (trade name: Elmiron) http://www.rarediseases.org/nord/search/nodd_full?code=356

•

Pantosan polysulfate sodium (trade name: Elmiron) http://www.rarediseases.org/nord/search/nodd_full?code=811

•

Mesna (trade name: Mesnex) http://www.rarediseases.org/nord/search/nodd_full?code=98

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

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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

235

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 Institute13: •

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/

13

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.14 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:15 •

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

14

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). 15 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

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

Augmentation Cystoplasty and Ileal Conduits in Pregnancy Source: International Urogynecology Journal. 6(1): 37-40. 1995. Contact: Available from Springer-Verlag New York, Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Fax (212) 473-6372. Summary: In this article, the authors report a case of successful pregnancy following augmentation cystoplasty in a patient who had refractory interstitial cystitis (IC). A review of the literature discusses the incidence of pyelonephritis, premature delivery, impaired urinary drainage, renal insufficiency, and the need for Cesarean section in pregnant patients who have had ileal conduits and augmentation cystoplasties. The authors conclude that careful urologic monitoring of such patients after urinary diversion or augmentation cystoplasty should result in a successful pregnancy. 2 tables. 21 references.

The NLM Gateway16 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.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “cystitis” (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.

16 17

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

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

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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 7090 72 142 22 1 7327

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 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.20 Simply search by “cystitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists21 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.22 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.23 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/.

18

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

19

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

20

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. 21 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 22

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

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

•

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

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on cystitis 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 cystitis. 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 cystitis. 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 “cystitis”:

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•

Other guides Bladder Cancer http://www.nlm.nih.gov/medlineplus/bladdercancer.html Bladder Diseases http://www.nlm.nih.gov/medlineplus/bladderdiseases.html Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.html Kidney Stones http://www.nlm.nih.gov/medlineplus/kidneystones.html Urinary Tract Infections http://www.nlm.nih.gov/medlineplus/urinarytractinfections.html Vaginal Diseases http://www.nlm.nih.gov/medlineplus/vaginaldiseases.html

Within the health topic page dedicated to cystitis, the following was listed: •

General/Overviews JAMA Patient Page: Urinary Tract Infections Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZMNZZTJAC &sub_cat=324 Urinary Tract Infection Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00286

•

Diagnosis/Symptoms Cystoscopy http://www.nlm.nih.gov/medlineplus/tutorials/cystoscopyloader.html Cystoscopy and Ureteroscopy Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/cystoscopy/index.htm Hematuria (Blood in the Urine) Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/hematuria/index.htm Painful Urination Source: American Academy of Family Physicians http://familydoctor.org/handouts/284.html Urinalysis Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/urinalysis/test.html

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Urination Problems: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/535.html Urine Culture Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/urine_culture/test.html •

Specific Conditions/Aspects Cystitis Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00285

•

Children Recurrent Urinary Tract Infections and Related Conditions Source: Nemours Foundation http://kidshealth.org/parent/medical/kidney/recurrent_uti_infections.html Treating Urinary Tract Infections Source: American Academy of Pediatrics http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZWW6H1R7C &sub_cat=107 Urinary Tract Infections (UTIs) Source: Nemours Foundation http://kidshealth.org/kid/ill_injure/sick/uti.html Urine Tests Source: Nemours Foundation http://kidshealth.org/parent/general/sick/labtest7.html Vesicoureteral Reflux Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/vesicoureteralreflux/index.htm

•

From the National Institutes of Health Urinary Tract Infections in Adults Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/utiadult/index.htm Urinary Tract Infections in Children Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/utichildren/index.htm What I Need to Know about Urinary Tract Infections http://kidney.niddk.nih.gov/kudiseases/pubs/uti_ez/index.htm

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Men Bladder Infections in Men Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HO00022

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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/ National Kidney and Urologic Diseases Information Clearinghouse Source: National Institute of Diabetes and Digestive and Kidney Diseases http://kidney.niddk.nih.gov/ UrologyHealth.org Source: American Urological Association http://urologyhealth.org/

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Research UTI Vaccine on the Horizon Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/about/Research_Updates/sum99/1.htm

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Statistics 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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Teenager All About Urinary Tract Infections Source: Nemours Foundation http://kidshealth.org/teen/infections/common/uti.html Kidneys and Urinary Tract Source: Nemours Foundation http://kidshealth.org/teen/your_body/body_basics/kidneys.html

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Women Keeping the Urinary System Healthy Source: American Medical Women's Association http://www.amwa-doc.org/publications/WCHealthbook/urinaryamwa-ch32.html Urinary Tract Infections Source: American College of Obstetricians and Gynecologists http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ1LJ5770D&s ub_cat=2008 Urinary Tract Infections During Pregnancy Source: American Academy of Family Physicians http://familydoctor.org/handouts/497.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the

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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 cystitis. 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: •

ICA: The Interstitial Cystitis Association Source: Rockville, MD: Interstitial Cystitis Association. 2000. [4 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for single copy; bulk copies available. Summary: Interstitial cystitis (IC) is a chronic inflammation of the bladder wall. This brochure discusses the symptoms, diagnosis, and treatment of IC and provides information about the work of the Interstitial Cystitis Association (ICA), a research and patient advocacy organization. Specific topics include urine testing; cystoscopy; bladder distention; oral medications; other drug therapy; diet therapy; surgery; and present initiatives of the ICA. The names and affiliations of the persons on the ICA Medical Advisory Board are listed, as is the address for the organization. A mail-in form to obtain more information is included.

•

Interstitial Cystitis and Diagnosis: Cystoscopy with Hydrodistention Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. [2 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFH01. Summary: Interstitial cystitis (IC) is considered a diagnosis of exclusion. IC is characterized by painful bladder symptoms in the absence of infection or other identifiable conditions. This fact sheet reviews the use of cystoscopy with hydrodistention as part of the diagnostic work up for IC. Diagnostic evaluation includes symptom history, urine culture to rule out bacterial infection, and tests to exclude other conditions such as pelvic inflammatory disease (PID), sexually transmitted diseases (STDs), or bladder cancer. After other disease processes have been excluded, the standard to confirm the diagnosis of IC is cystoscopy with hydrodistention of the bladder under general or regional anesthesia. This procedure involves slowly stretching the bladder with fluid, thereby allowing the physician to see changes that are typical of IC. The fact sheet explains exactly what the patient can expect during and after the cystoscopy procedure. Hydrodistention itself may reduce pain and discomfort in some IC patients, and therefore may be therapeutic as well as diagnostic. The fact sheet

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includes the contact information for the Interstitial Cystitis Association (ICA, www.ichelp.org). •

Interstitial Cystitis and Self-Help Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2000. [4 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 plus shipping and handling. Summary: Living with interstitial cystitis (IC) is a challenge which requires creativity, patience, and determination. Because there is no cure for IC or an effective treatment that works for everyone, people with IC discover that they must take an active role in managing their lives. This brochure outlines a variety of suggestions to help readers live with IC on a daily basis. The information provided was compiled from a series of questionnaires completed by people with IC and their doctors, as well as from publications available through the Interstitial Cystitis Association (ICA). The brochure covers diet, exercise, reducing stress, pain relief, sexuality, clothing, products, travel, restroom access, nontraditional treatments, and taking control. Many IC patients find that diet plays an important role in helping them control the condition and avoid flare ups. Most people with IC recognize that stress plays a part in exacerbating symptoms or bringing on flare ups; of course, IC and the accompanying symptoms are a source of stress in themselves. Exercise can be used to combat stress and relieve pain. Wearing clothes that are comfortable and nonrestrictive can provide basic relief for IC patients. The brochure concludes with a list of other brochures available from the Interstitial Cystitis Association (ICA), a list of resources and references, a description of the activities of the ICA, and a list of the members of the ICA Medical Advisory Board.

•

Interstitial Cystitis and the Potassium Chloride Sensitivity Test Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2003. 2 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 N. Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers. Item number RFKCL01. Summary: Many interstitial cystitis (IC) patients have expressed their concerns regarding the usefulness of the potassium chloride sensitivity test (also known as the KCI test or Parsons test) in diagnosing and treating IC. The Interstitial Cystitis Association (ICA) has also received comments from patients regarding the pain induced by the test. More and more patients report that their physicians are relying on this test to diagnose IC and to predict their response to medications. However, careful investigation and consideration of all available information regarding the KCI test must be taken into account before accepting the validity of the test. This test has yet to be proven or accepted as a diagnostic or predictive IC test. This fact sheet reviews the KCI test and how it is used. The fact sheet includes the contact information for the ICA (www.ichelp.org). 12 references.

•

Interstitial Cystitis and Diet Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. [4 p.].

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Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 plus shipping and handling. Summary: Many patients with interstitial cystitis (IC) find that dietary modifications help to control their symptoms and avoid flare ups. Others find that what they eat or drink seems to have little effect on how they feel. This brochure guides readers with IC in a determination of which foods may act as triggers in their own situation. The author stresses that discovering which particular foods may cause problems requires persistence, but many IC patients report that restricting their diet is an effective form of treatment and well worth the effort. The brochure guides readers in the use of an elimination diet, encouraging the use of a food diary as a technique for monitoring diet. The brochure offers lists of foods to avoid and those to try in each of ten categories: milk and dairy products, vegetables, fruits, carbohydrates and grains, meats and fish, nuts, beverages, seasonings, preservatives and additives, and miscellaneous. The author notes that after the reader has completed the work of determining which foods to eliminate from the diet, the reader may find that some of the troublesome items can be tolerated on a rotation basis. The brochure also includes suggestions for dining out, managing food allergies, and handling food associated problems. The brochure concludes with a list of other brochures available from the Interstitial Cystitis Association (ICA), a list of resources and references, a description of the activities of the ICA, and a list of the members of the ICA Medical Advisory Board. •

Interstitial Cystitis and Social Security Disability Insurance Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. 1 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFI01. Summary: Social Security Disability Insurance (SSDI) is a Federal insurance program, financed through payroll withholding, that covers most American workers. SSDI was designed to help people meet their financial obligations and obtain necessary medical treatment. This fact sheet reviews the use of SSDI for people with interstitial cystitis (IC). Topics include why SSDI might be necessary, how SSDI works, who is eligible for SSDI, information needed to submit a claim, and what happens once a claim is submitted. In order to submit a claim, patients should identify their impairments and the medical condition(s) they think are responsible for their impairments; identify medical treatment sources; describe any medication or therapy they are taking and side effects; describe activities of daily living and education; and describe their jobs of the past 15 years and their major physical and mental demands. A thorough medical report from the doctor, addressing in detail their specific disability, is essential. The fact sheet notes the services of the Interstitial Cystitis Association (ICA), including documents that can support SSDI claims.

•

Urinary Tract Infections in Children: Why They Occur and How to Prevent Them Source: American Family Physician. 57(10): 2448-2750. May 15, 1998. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org.

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Summary: This article offers a general overview of urinary tract infections (UTIs) in children and how to prevent them. The author first lists the anatomical parts of the urinary tract and then addresses basic questions about how UTIs occur and how to prevent them. The urinary tract normally does not have bacteria in it, except at the very end of the urethra and on the skin around the opening of the urethra. When harmful bacteria get into the urinary tract, though, they can cause an infection. Urinary tract infections include bladder infections (cystitis), and kidney infections (pyelonephritis). UTIs are sometimes hard to diagnose in babies and young children, as they cannot explain where it hurts. Older children may say that it hurts to urinate, may have a sudden need to urinate, or may hold themselves or squat to keep from urinating. UTIs are diagnosed with a urine culture. Children who have had numerous UTIs, particularly kidney infections, will be tested with an x-ray or sonogram for problems that could be contributing to the infections. The article concludes with a list of good bathroom habits for parents to teach children to follow. These include teaching girls to wipe from front to back, teaching boys to completely open their pants and underpants so the penis is not pressed by clothing when urinating, teaching all children to urinate regularly, treating constipation, and giving children antibiotics only when indicated. 1 figure. •

Interstitial Cystitis: Hydrodilation and Endoscopic Changes Source: West Haven, CT: Miles, Inc., Pharmaceutical Division. 1992. 7 p. Contact: Available from Mile, Inc. Pharmaceutical Division. 400 Morgan Lane, West Haven, CT 06516. (800) 468-0894. PRICE: Free. Summary: This booklet details the procedure of hydrodilation, performed to treat interstitial cystitis (IC). The author discusses epithelial dysfunction and IC and then provides a detailed, step-by-step guide to the hydrodilation technique and the endoscopic findings to be expected. An additional section briefly covers dimethylsulfoxide (DMSO) therapy and intravesical heparin used for DMSO failure. Full-color endoscopic photographs illustrate each of the procedural steps discussed. The booklet concludes with a list of related questions and answers. 7 figures.

•

Interstitial Cystitis and Finding the Right Physician for You Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. [1 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFF01. Summary: This brief fact sheet reviews strategies for finding a physician to help a patient deal with interstitial cystitis (IC). This is important because successfully managing a chronic illness like IC depends, in part, on the choice of physician and the attributes that physician brings to the process. Effective treatments are enhanced by a knowledgeable, compassionate physician. Patient goals include finding a physician who is knowledgeable of and interested in treating IC; who will provide an accurate diagnosis, appropriate treatments, and ongoing care; and who will educate the patient about treatment options, take time to listen, work collaboratively with the patient, and respect the knowledge the patient has about IC. The fact sheet lists suggested questions to ask the physician at the initial appointment and questions regarding diagnostic testing, treatment, and management of IC. One sidebar lists patient rights as they relate to physician patient relations and delivery of health care. The fact sheet includes the contact information for the Interstitial Cystitis Association (ICA). 1 reference.

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Interstitial Cystitis and Elmiron Source: Rockville, MD: Interstitial Cystitis Association (ICA). 1999. [1 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 plus shipping and handling. Summary: This brief fact sheet reviews the use of Elmiron, an oral prescription drug that may be used to treat interstitial cystitis (IC). Elmiron may work by restoring a damaged, thin, or 'leaky' bladder surface, but the drug's mechanical action in IC is unknown. Of patients treated with Elmiron for 3 months, 38 percent reported improvement of their IC symptoms. The fact sheet reviews the administration and dosage of the drug, the side effects, availability of the medication, and indications for women who are pregnant. The side effects of Elmiron are minimal, limited primarily to minor gastrointestinal disturbances; a few patients have also experienced hair loss that is reversible upon discontinuing the drug. Because adequate and well controlled studies have not been performed in pregnant women, the manufacturer recommends that the drug should be used in pregnancy only if clearly needed. The safety and effectiveness of Elmiron use in children has not been established. In the fall of 1996, the FDA granted marketing clearance to Elmiron. It costs about $160 for a 1 month supply of the drug. The fact sheet includes the contact information for the Interstitial Cystitis Association (ICA). 3 references.

•

Interstitial Cystitis and Men Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2000. [4 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 plus shipping and handling. Summary: This brochure describes interstitial cystitis (IC) in men, a chronic inflammatory condition of the bladder wall. Unlike common cystitis, IC is believed not to be caused by bacteria and does not respond to conventional antibiotic therapy. The brochure notes that IC is not a psychosomatic disorder, nor is it caused by stress. IC is diagnosed far less often in men than it is in women (approximately 10 percent of all patients with IC are men). The symptoms can include urinary frequency, urgency, and scrotal pain. Most patients have difficulty obtaining a diagnosis, and men are often misdiagnosed as having chronic prostatitis. It is very important for male patients to have a thorough diagnostic workup, including hydrodistention and cystoscopy of the bladder under general or regional anesthesia. The brochure reviews the treatments for IC, including oral medications (Elmiron, antidepressants, antiinflammatory agents, and others), bladder instillations (bladder distention, DMSO, BCG, Cystistat, heparin), and other treatments, including diet, self help techniques, electronic nerve stimulators, and surgery. The brochure concludes with a brief description of the Interstitial Cystitis Association (ICA) and its activities. 3 references.

•

Urethral Syndrome: Interstitial Cystitis Source: Marietta, GA: GU Logic. 1994. 2 p. Contact: Available from GU Logic. 2470 Windy Hill Road, Suite 108, Marietta, GA 30067. (800) 451-8107. PRICE: $35 for 50 copies. Order Number: GU100.

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Summary: This brochure describes urethral syndrome, a primarily female syndrome in which women suffer from irritative bladder symptoms in the absence of any objective urologic findings. The brochure discusses the symptoms, etiology, diagnosis and treatment of urethral syndromeme. In addition, one section briefly discusses interstitial cystitis, an inflammatory condition of the bladder, and its treatment. The brochure reminds patients of the difficulties of diagnosing these conditions and encourages patients to work together with their health care provider for the successful diagnosis and treatment of these problems. •

Questions and Answers on Urinary Tract Infections Source: Alexandria, VA: American Medical Women's Association. 1997. 4 p. Contact: Available from American Medical Women's Association. 801 North Fairfax Street, Alexandria, VA 22314. (781) 585-8220. PRICE: Single copy free. Summary: This brochure outlines symptoms, diagnosis, and treatment of urinary tract infections (UTIs). An infection of the urinary tract commonly has the following symptoms: frequent and urgent need to urinate, painful urination, cloudy urine, lower back or abdominal pain, blood in the urine. About 80 to 90 percent of UTIs are caused by Escherichia coli bacteria, which are normally present in the rectum. Factors that may contribute to UTIs are sexual intercourse, some birth control methods, low water intake, and anatomic problems. The first step a health care provider will take to confirm a bacterial UTI is to review the symptoms and test the patient's urine. The infection should be diagnosed by a urine culture, since several other conditions, including vaginal infections, gonorrhea, chlamydia, irritable bladder, and bladder cancer, can have similar symptoms. When pain is the predominant symptom, the diagnosis may be interstitial cystitis. If the urine culture shows bacteria, the health care provider will prescribe a course of antibiotics. The brochure outlines other steps to take to treat a UTI, including drinking large amounts of water; avoiding caffeine, acid foods, spices, citrus fruits, tomatoes, alcohol, and chocolate; drinking cranberry juice cocktail; and trying hot water bottles or heating pads to ease cramps and soothe the pain. The brochure concludes with a section of suggestions for preventing UTIs, including drinking plenty of fluids, wiping from 'front to back' (vagina to anus) after urinating to avoid spreading bacteria, scheduling frequent bathroom breaks, drinking water before and after sex in order to ensure a good volume of urination afterward, checking the fit of a diaphragm or using another method of birth control, avoiding tight clothing and pantyhose, and wearing cotton underwear.

•

Taking Care of Urinary Tract Infections Source: Santa Cruz, CA: ETR Associates. 1998. 6 p. Contact: Available from ETR Associates. 4 Carbonero Way, Scotts Valley, CA 950664200. (800) 321-4407. Fax (800) 435-8433. Website: www.etr.org. PRICE: Single copy free; $16.00 for 50 copies, discounts for larger orders. Order number: R024. Summary: This brochure provides basic information about urinary tract infections (UTIs) in men and women. A UTI is caused when bacteria enter the urinary tract and can be called urethritis (in the urethra), cystitis (in the bladder), or pyelonephritis (in the kidney). Any UTI symptoms should be checked by a health care provider, since untreated UTIs can result in more serious problems. The brochure describes the differences between UTIs in men and in women. The brochure also lists common symptoms of the different types of UTIs. These symptoms include pain or burning when urinating, feeling a sudden urgent need to urinate, urinating more often then usual,

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urinating only small amounts even though the bladder feels full, blood in the urine, cloudy or foul smelling urine, and pain. Sidebars consider the role of sexually transmitted diseases (STDs) in urinary tract infections. The brochure briefly reviews the treatment protocol for UTI, which includes a genital or pelvic exam, a urinalysis, and possible prescription for antibiotics. The brochure also outlines home care strategies for resolving a UTI more quickly, including drinking plenty of water, refraining from sexual activities, getting plenty of rest, limiting foods that may cause urinary burning (such as coffee, tea, alcohol, spicy foods), and using over the counter medications that can help with bladder pain. The brochure concludes with a list of strategies to help avoid UTIs, as well as a summary of the symptoms that indicate the need to contact a health care provider. 2 figures. •

Urinary Tract Infections: Guide for Women Source: Washington DC: National Kidney Foundation of the National Capital Area. 199x. 2 p. Contact: Available from National Kidney Foundation of the National Capital Area. 5335 Wisconsin Avenue, Suite 830, Washington DC 20015-2030. PRICE: Single copy free. Summary: This brochure provides readers with a basic overview of urinary tract infections (UTIs). Topics include the two kinds of UTIs (acute cystitis and pyelonephritis); UTI symptoms; how to know when to consult a health care provider; situations where UTI symptoms can mask a more serious condition; considerations during pregnancy; how UTIs are treated; and what patients can do to prevent recurrence of UTIs. The brochure concludes with the contact information for both national and local National Kidney Foundation offices. The brochure is also available in a version designed for people with low literacy skills (see KU BR 05337).

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Interstitial Cystitis and Over-the-Counter Products and Medications Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2003. 2 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 N. Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: Full-text available online at no charge. Summary: This fact sheet considers the several over-the-counter (OTC) products and medications currently available that may be useful for interstitial cystitis (IC). Products are organized into four sections: to help reduce bladder symptoms, reduced acid foods and beverages, to help with sexual intimacy, and other helpful products. In the first section, the fact sheet briefly describes Prelief (dietary supplement), aloe vera, Cysta-Q and Prosta-Q (bioflavenoids), traditional Chinese herbal remedies, Algonot-Plus (glucosamine, chondroitin, and quercetin combination), and Tamer (natural supplements containing calcium carbonate, potassium and magnesium hydroxides). The second section includes Cafix (a coffee substitute), acid reduced coffees and teas, acidreduced orange juice, Puroast coffee (lower acid coffee), and Natural Touch Roma (a multigrain beverage). The fact sheet includes the contact information for the ICA (www.ichelp.org).

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Interstitial Cystitis and InterStim Therapy Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. 2 p.

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Contact: Available from Interstitial Cystitis Association (ICA). 110 N. Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers. Item number: RFIS01. Summary: This fact sheet describes a new, experimental treatment for interstitial cystitis (IC), a chronic inflammatory condition of the bladder. The neuromodulation device (InterStim Therapy) is now being considered as a potential IC treatment when other more conservative therapies have failed. InterStim is approved by the Food and Drug Administration (FDA) for urinary urge incontinence, nonobstructive urinary retention, and significant symptoms of urgency-frequency in patients who have failed to respond to more conservative treatments. InterStim is not yet approved for the treatment of IC. InterStim consists of a small, surgically implanted device that is used to send mild electrical pulses to nerves located in the lower back (sacral nerves, just above the tailbone). The fact sheet reviews in detail how InterStim works, test stimulation, the neuromodulator, how to find out more about InterStim, potential adverse events, and contraindications. The fact sheet concludes with the answers to commonly asked questions about InterStim. Readers are referred to the Interstitial Cystitis Association (www.ichelp.org) for more information. 2 references. •

Interstitial Cystitis and Constipation Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. 2 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 N. Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers. Item number: RFQ01. Summary: This fact sheet describes the interrelationship between constipation and interstitial cystitis (IC), a chronic inflammatory condition of the bladder. The fact sheet considers the possible causes of constipation in IC patients, why constipation can be a concern in patients with IC, methods for alleviating constipation in patients who do not have irritable bowel syndrome (IBS) or who are not coping with medication-related constipation, and methods for alleviating constipation that is related to IBS. Readers are referred to the Interstitial Cystitis Association (www.ichelp.org) for more information. 4 references.

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Bladder Infection, Male (Cystitis in Men) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 44. 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 cystitis in men 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 reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish.

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Bladder Infection, Female (Cystitis in Women) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 43. 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 cystitis in women 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 reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish.

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Interstitial Cystitis and Surgical Procedures Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. [2 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFS01. Summary: This fact sheet presents an overview of surgical procedures that interstitial cystitis (IC) patients may choose to consider. Bladder surgery is generally considered the treatment of last resort by IC patients and their doctors. The obvious reason is that surgery is invasive and irreversible, but in addition, many patients who choose to have surgery may not improve. Some patients, in fact, do worse after surgery. Potential complications from these procedures also need to be considered. Researchers have pointed out that with an ever enlarging array of treatment options available to the IC patient, surgery should be considered only when all other choices have failed. The fact sheet stresses that readers should consult a urologist experienced in treating IC for advice about surgical options. Types of bladder surgery described are augmentation cystoplasty, urinary diversion, internal pouch (Kock pouch), and orthotopic diversion. The fact sheet also describes laser surgery, which is sometimes indicated for the ulcerative form of IC. The fact sheet includes a surgery checklist, a list of questions to ask the doctor when considering surgery. The fact sheet includes the contact information for the Interstitial Cystitis Association (ICA), with their website (www.ichelp.org). 1 table. 6 references.

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Interstitial Cystitis and Bladder Retraining Program Source: Rockville, MD: Interstitial Cystitis Association. 2001. 1 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFB01. Summary: This fact sheet reviews the bladder retraining program that is utilized with patients who have interstitial cystitis (IC). The bladder retraining program is a self help process by which patients who have urinary urgency or frequency can learn to control

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their urge to urinate in an attempt to improve their symptoms. The fact sheet outlines the rationale for the program, how the process works, who can benefit, clinical studies that support the use of the program, drawbacks to the program, and adjunctive therapies that can be used. Under the direction of a urologist, the program is established for each patient beginning with a 4-week period of holding the urine for a certain number of minutes or hours (based on the individual's current average voiding schedule). The patient is encouraged to wait a specified period after the first urge is felt before urinating (15 minutes, for example). If after waiting, the patient finds that the need to urinate has diminished, then he or she should wait until the next urge to void is felt. At the end of 1 month, the time interval is increased, and at the end of the second month, the interval is increased again. The fact sheet stresses that the relatively long time period (average 3 months) required for success can contribute to patient dissatisfaction and noncompliance. The program can be particularly successful when special attention is paid to the patient, including the employment of a medical social worker to encourage the patient's belief in the method, as well as an understanding that this does not provide an 'instant cure'. 3 references. (AA-M). •

Interstitial Cystitis and Other Diseases Source: Rockville, MD: Interstitial Cystitis Association. 2001. 1 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFO01. Summary: This fact sheet reviews the interrelationship of non-urological medical conditions and interstitial cystitis (IC). IC is characterized by a number of symptoms (urinary urgency, frequency, suprapubic pain, diminished bladder capacity) which can affect IC patients in varying combinations or in varying degrees of intensity. In addition, it has been noted that certain types of medical conditions seem to occur in IC patients more frequently than they do in individuals without IC. The fact sheet outlines the correlation between IC and irritable bowel syndrome (IBS), allergies, and sensitive skin. The fact sheet briefly quotes related research studies, and includes the contact information for the Interstitial Cystitis Association (ICA). 3 references. (AA-M).

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Interstitial Cystitis and Heparin Source: Rockville, MD: Interstitial Cystitis Association. 2001. 1 p. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFP01. Summary: This fact sheet reviews the use of heparin for treating patients who have interstitial cystitis (IC). IC is characterized by a number of symptoms (urinary urgency, frequency, suprapubic pain, diminished bladder capacity) which can affect IC patients in varying combinations or in varying degrees of intensity. Heparin is a compound that has both antiinflammatory and surface protective actions. Heparin can mimic the activity of the bladder's mucous lining. It can be used as a primary treatment method or as a maintenance medication to supplement other types of treatment. The fact sheet outlines treatment using heparin and briefly considers clinical studies that support its use and compare it to the use of DMSO instillation. The side effects of instilled heparin are limited primarily to pain, irritation, or discomfort resulting from frequent

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catheterization. The fact sheet includes contact information for the Interstitial Cystitis Association (ICA). 3 references. (AA-M). •

Simple Cystitis: Patient Education Source: Tarrytown, NY: Bayer Corporation. 1999. 7 p. Contact: Available from Bayer Corporation. Diagnostics Division, 511 Benedict Avenue, Tarrytown, NY 10591-5097. (800) 445-5901. PRICE: Single copy free. Summary: This patient education brochure reviews cystitis, inflammation of the bladder, usually due to bacterial infection. The brochure defines the condition, describes risk factors and causes, outlines the diagnostic approaches that may be used, reviews treatment options, and offers suggestions for prevention. Although anyone can be affected by simple cystitis, it most commonly occurs in women of childbearing age. Symptoms of cystitis include a burning sensation when urinating, frequent or urgent need to urinate, and blood in the urine. Other causes of simple cystitis include certain medications and radiation therapy; this brochure focuses on cystitis caused by bacterial infection. Simple cystitis is diagnosed by urinalysis, which examines a sample of the patient's urine for bacteria, blood, and pus. Another test (urine culture and sensitivity) determines the presence of bacteria and their sensitivity to various antibiotics. Three to seven days of antibiotic therapy is the usual course of treatment for cystitis. The brochure lists suggestions for preventing simple cystitis, including urinating after sexual intercourse, avoiding products that can irritate the urinary area, urinating at least every 4 to 6 hours during the day, seeking treatment from the doctor for any symptoms of urinary incontinence (involuntary leakage), drinking at least 6 to 8 glasses per day, wearing cotton underwear, avoiding clothing that is tight in the crotch, and, after urinating or defecating, wiping from front to back. The brochure answers common questions about cystitis and its management. The brochure concludes with a brief glossary of terms and a short list of resources for readers wishing to obtain additional information. A tear-off section lists the topics covered in the booklet; readers are encouraged to check off the items corresponding to issues they would like to discuss with their health care provider, to use the checklist as a reminder tool.

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Urinary Tract Infections Source: Emeryville, CA: Parlay International. 1997. [4 p.]. Contact: Available from Parlay International. Box 8817, Emeryville, CA 94662-0817. (800) 457-2752. Website: www.parlay.com. PRICE: $20.00 per package of 50. Order number: 7026. Summary: Urinary tract infection is a common problem affecting men, women, and children; women are more prone to developing the infection due to the structure of their urinary system. This brochure provides basic information about urinary tract infections (UTIs), emphasizing the importance of recognizing the symptoms and obtaining prompt medical assistance. The brochure outlines the female urinary tract (a simple drawing is included) and the function of each organ in the urinary tract. The bladder and urethra make up the lower urinary tract and are the most common site for infection. Bladder infection, commonly known as cystitis, is usually mild. By seeking medical attention promptly, a variety of antibiotic treatments can be administered to help prevent further discomfort and effect a rapid cure. The majority of cases of UTIs exhibit three common symptoms: discomfort or burning during urination, feeling the need to urinate more than usual, and frequent urination (often in small amounts). Other symptoms may include lower back and side pain and lower abdominal soreness or slight fever, which

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are also possible signs of a kidney infection. The brochure briefly describes the use of urinalysis to pinpoint diagnosis and therefore optimize therapy. Various antibiotic treatments are available, depending on the individual's condition. Repeat UTI is not uncommon. Some people achieve relief with prescribed preventive antibiotic therapy. The brochure reiterates the importance of recognizing the symptoms and getting medical care, not attempting to self-treat. 1 figure. •

Understanding Urinary Tract Infections: Treatment and Prevention for Women and Men Source: San Bruno, CA: StayWell Company. 1999. 7 p. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. E-mail: [email protected]. Website: www.staywell.com. PRICE: $1.10 per copy; plus shipping and handling. Summary: Urinary tract infections (UTIs) are common in both women and men. This brochure helps patients diagnosed with UTIs to understand their infection and how to treat it. The booklet stresses that an early diagnosis offers the best chance for successful treatment and helps prevent the infection from turning into a more serious problem (such as kidney infection). Diagnosis can include medical history, physical exam, and laboratory tests, including urinalysis, urine culture, blood tests, kidney ultrasound, intravenous pyelogram (IVP, an x ray of the kidney), cystoscopy, and cystogram (a x ray of the bladder, ureter, or urethra). The brochure briefly reviews the anatomy of the urinary tract and how UTIs occur, including sexual behavior, poor hygiene, urine that remains in the bladder after urination, a blockage in the kidneys, and a blockage caused by an enlarged prostate (in men). There are different kinds of UTIs, including cystitis (bladder infection) in women, urethral syndrome in women, pyelonephritis in men and women, prostatitis in men, urethritis in men, and cystitis in men. Treatment and prevention strategies include taking medications as directed, drinking enough fluids, practicing good personal hygiene, emptying bladder whenever the urge to urinate is present, avoiding foods that may irritate the urinary tract, and keeping followup medical appointments. Occasionally, surgery may be necessary to relieve blockages, such as an enlarged prostate or kidney stone. The brochure is illustrated with full color line drawings. 25 figures.

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Urinary Tract Infections in Young Children Source: Elk Grove Village, IL: American Academy of Pediatrics. 1999. [4 p.]. Contact: Available from American Academy of Pediatrics. Division of Publications, 141 Northwest Point Blvd., P.O. Box 747, Elk Grove Village, IL 60009-0747. (800) 433-9016. Fax (847) 228-1281. E-mail: [email protected]. Website: www.aap.org. PRICE: $34.95 per pack of 100 brochures (nonmembers); $29.95 per pack of 100 brochures (members). Summary: Urinary tract infections are common in infants and young children: about 3 percent of girls and 1 percent of boys will have a UTI by 11 years of age. This brochure provides information about urinary tract infections (UTIs) in young children. Written for parents, the brochure notes that UTIs in this population may go untreated because the symptoms may not be obvious to the child or to parents. The brochure first briefly describes the anatomy of the urinary tract and the different infections caused by bacteria, including urethritis (urethral infection), cystitis (bladder infection), and pyelonephritis (kidney infection). Symptoms of UTIs may include the following: fever, pain or burning during urination, the need to urinate more often, difficulty getting urine out, bedwetting, vomiting (or refusal to eat), abdominal pain, side or back pain, foul-

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smelling urine, cloudy or bloody urine, unexplained and persistent irritability in an infant, or poor growth in an infant. The diagnostic workup includes a history of the child's symptoms, a review of the food and fluid intake, a physical examination, and a urinalysis (test of a urine sample from the child). The brochure describes the ways that a urine sample is obtained from a young child. UTIs are treated with antibiotics; infants and young children with UTIs usually need to take antibiotics for 7 to 14 days, sometimes longer. The brochure describes followup care, including the use of diagnostic tests to make sure the urinary tract is normal and that the infection did not cause any damage. These tests include kidney and bladder ultrasound, voiding cystourethrogram (VCUG), intravenous pyelogram, and nuclear scans. The brochure also briefly describes some of the other publications that are available from the American Academy of Pediatrics. 2 figures. •

Urinary Tract Infection Source: New York, NY: National Kidney Foundation, Inc. 1990. 4p. Contact: National Kidney Foundation, Inc. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. PRICE: Single copy free. Order No. 08-53. Summary: Written in a question and answer format, and using an anatomical diagram, this brochure defines and discusses the symptoms, causes, diagnosis, treatment and prevention of urinary tract infection. Special attention is given to the occurrence of urinary infection in children and women. Urine tests are used to detect the bacteria that has invaded the kidneys, bladder or urinary pathways. The National Guideline Clearinghouse™

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

Evidence based clinical practice guideline for patients 6 years of age or less with a first time acute urinary tract infection (UTI) Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 1999 March 28 http://www.guideline.gov/summary/summary.aspx?doc_id=1970&nbr=1196&a mp;string=cystitis

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Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women Source: Infectious Diseases Society of America - Medical Specialty Society; 1999 October; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2671&nbr=1897&a mp;string=cystitis

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The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children Source: American Academy of Pediatrics - Medical Specialty Society; 1999 April 5; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1838&nbr=1064&a mp;string=urinary+AND+tract+AND+infection

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Urinary tract infection Source: University of Michigan Health System - Academic Institution; 1999 June; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2284&nbr=1510&a mp;string=cystitis 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: •

Interstitial Cystitis Summary: This text is for people who have interstitial cystitis and for relations, friends, and coworkers who want to understand the experiences and challenges associated with the disorder. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=828 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 cystitis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

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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

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Associations and Cystitis The following is a list of associations that provide information on and resources relating to cystitis: •

Interstitial Cystitis Association of America, Inc Telephone: (301) 610-5300 Toll-free: (800) 435-7422 Fax: (301) 610-5308 Email: [email protected] Web Site: http://www.ichelp.org Background: The Interstitial Cystitis Association of America (ICA) is a voluntary notfor-profit organization working on behalf of all individuals with interstitial cystitis (IC), an inflammatory disease of the bladder in which chronic inflammation of the lining of the bladder and swelling of the bladder s interior walls result in pressure and pain above the pubic area and frequency and urgency of urination. Established in 1984 by individuals with interstitial cystitis, the Association is dedicated to providing affected individuals with the most current information on the disease; offering a support network to affected individuals and their families; increasing awareness of the disease among the medical community and the general public; and establishing a National Database to compile and study data concerning interstitial cystitis and promote research to find an effective treatment and cure for IC. The Interstitial Cystitis Association of America also promotes patient advocacy; testifies before Congress to support legislation beneficial to people with IC; funds several research projects for Interstitial Cystitis including its own Pilot Research Project Program; and conducts ICA national meetings and scientific workshops for Interstitial Cystitis researchers. It offers a variety of materials to affected individuals and the medical community including a regular newsletter entitled 'Update,' reports, journal article reprints, transcripts of workshops, brochures, videos, and audiotapes.

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Interstitial Cystitis Information Center Telephone: (804) 315-0060 Toll-free: (800) 758-1494 Fax: (804) 315-0291 Email: [email protected] Web Site: http://www.moonstar.com/~icickay Background: The Interstitial Cystitis Information Center, founded and directed by a former IC patient, is dedicated to providing information, assistance and support to men and women with interstitial cystitis (IC). IC is usually characterized as an inflammatory disease of the bladder because of the usual symptoms of pressure and pain above the

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pubic area as well as abnormal frequency and urgency of urination. It is thought that IC might be bacterial, hormonal or diet and stress related. Each person with IC is unique with his/her symptoms and the difficulty lies in finding out what 'kind' of IC each person may have. The ICIC does not believe in any invasive tests or treatments. Established in 1995, it offers hope for healing to those afflicted and advocates on behalf of affected individuals and family members. The ICIC maintains a database of information which now can be downloaded FREE from its website. It recommends alternative forms of therapy to IC patients, many of whom have lost hope having tried and failed with numerous traditional therapies. The ICIC is working with researchers to learn the possible causes of IC and promotes professional and public education on IC.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to cystitis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with cystitis. 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 cystitis. 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 “cystitis” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

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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 “cystitis”. 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 “cystitis” (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 “cystitis” (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.24

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

24

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)25: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

25

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

Finding Medical Libraries

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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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries

267

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

269

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

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

•

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

•

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

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on cystitis: •

Basic Guidelines for Cystitis Cystitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000521.htm Cystitis - acute bacterial Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000526.htm Cystitis - noninfectious (acute urethral syndrome) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000514.htm

•

Signs & Symptoms for Cystitis Abnormal urine color Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003139.htm Blood in the urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm

270 Cystitis

Bowel incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003135.htm Chills Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003091.htm Cloudy urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Dysuria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003145.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Flank pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003113.htm Frequent need to urinate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Frequent urination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Hematuria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Mental changes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle contractions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Need to urinate at night Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm Penis pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003166.htm

Online Glossaries 271

Sexual intercourse, painful Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003157.htm Urgent need to urinate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Urination, painful Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003145.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Cystitis Catheterized urine specimen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003752.htm Cystoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003903.htm Heart rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm RBC - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003582.htm RBC; urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003582.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm Urine culture (clean catch) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003751.htm Urine odor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003431.htm WBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003643.htm

•

Nutrition for Cystitis Ascorbic acid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002404.htm Caffeine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002445.htm

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•

Background Topics for Cystitis Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Kegel exercises Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003975.htm Pelvic muscle strengthening exercises Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003975.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

273

CYSTITIS 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] Abdominal Cramps: Abdominal pain due to spasmodic contractions of the bowel. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [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] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH]

274 Cystitis

Acute tubular: A severe form of acute renal failure that develops in people with severe illnesses like infections or with low blood pressure. Patients may need dialysis. Kidney function often improves if the underlying disease is successfully treated. [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] 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 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] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] 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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] 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] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with

Dictionary 275

similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aeroembolism: Joint pains, respiratory distress, and central nervous system symptoms which may follow decompression after exposure to air or other gas mixture at a pressure greater than the normal atmospheric pressure. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airways: Tubes that carry air into and out of the lungs. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure

276 Cystitis

and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylate: To treat with an alkylating agent. [EU] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Aloe: A genus of the family Liliaceae containing anthraquinone glycosides such as aloinemodin or aloe-emodin (emodin). [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] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and

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atomic weight 26.98. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [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] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anal Fissure: A small tear in the anus that may cause itching, pain, or bleeding. [NIH]

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Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

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Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms.

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[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] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH]

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Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arthralgia: Pain in the joint. [NIH] Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. [NIH] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH]

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Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] 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

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such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Bends: The form of aeroembolism that is marked by intense pain in muscles and joints due to formation of gas bubbles in the tissues. [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] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH]

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Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [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] Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Blind spot: (1) A small area of the retina where the optic nerve enters the eye; occurs normally in all eyes.(2) Any gap in the visual field corresponding to an area of the retina where no visual cells are present; associated with eye disease. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH]

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Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a

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pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Calendula: Genus of annuals in the family Asteraceae that contains carotenoids, essential oils (oils, volatile), flavonoids, mucilage, saponins, and sterols. It is used both topically and internally. [NIH] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH]

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Carbapenems: A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. [NIH]

Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carboprost: An abortifacient effective in both the first and second trimesters of pregnancy. [NIH]

Carboxy: Cannabinoid. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH]

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Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [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 Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions

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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] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [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] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cephaloridine: A cephalosporin antibiotic. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cephalothin: A cephalosporin antibiotic. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [NIH]

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Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Checkup: A general physical examination. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in 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 Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic prostatitis: Inflammation of the prostate gland, developing slowly and lasting a long 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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2

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receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [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] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [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

292 Cystitis

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] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative

Dictionary 293

pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [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] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective

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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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [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]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH]

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Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cromolyn Sodium: A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack. [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] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH]

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Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystectomy: Used for excision of the urinary bladder. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystinuria: An inherited abnormality of renal tubular transport of dibasic amino acids leading to massive urinary excretion of cystine, lysine, arginine, and ornithine. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cystometrogram: A line graph that records urinary bladder pressure at various volumes. [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 and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH]

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Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dermatitis: Any inflammation of the skin. [NIH] 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]

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Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] 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] Dilator: A device used to stretch or enlarge an opening. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discriminant Analysis: A statistical analytic technique used with discrete dependent variables, concerned with separating sets of observed values and allocating new values. It is sometimes used instead of regression analysis. [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

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to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diverticula: Plural form of diverticulum. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH]

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Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Dysuria: Painful or difficult urination. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] 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] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] 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]

Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH]

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Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emodin: Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [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] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [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] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph

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vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] 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] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Factors: Events, characteristics, or other definable entities that have the potential to bring about a change in a health condition or other defined outcome. [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]

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Epidemiological: Relating to, or involving epidemiology. [EU] 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] 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 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] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU]

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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] Exfoliation: A falling off in scales or layers. [EU] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]

Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [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,

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characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] 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] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] 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 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] Flank Pain: Pain emanating from below the ribs and above the ilium. [NIH] Flatus: Gas passed through the rectum. [NIH]

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Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] 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] Foetoplacental: Pertaining to the fetus and placenta. [EU] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fosfomycin: An antibiotic produced by Streptomyces fradiae. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungicide: An agent that destroys fungi. [EU] 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] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored

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in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] 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] Genes, Bacterial: The genetic material of bacteria. [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,

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transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gentian Violet: A dye that is a mixture of violet rosanilinis with antibacterial, antifungal, and anthelmentic properties. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [NIH] Globosides: Glycosphingolipids containing N-acetylglucosamine (paragloboside) or Nacetylgalactosamine (globoside). Globoside is the P antigen on erythrocytes and paragloboside is an intermediate in the biosynthesis of erythrocyte blood group ABH and P 1 glycosphingolipid antigens. The accumulation of globoside in tissue, due to a defect in hexosaminidases A and B, is the cause of Sandhoff disease. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH]

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Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycerophosphates: Any salt or ester of glycerophosphoric acid. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosuria: The presence of glucose in the urine; especially the excretion of an abnormally large amount of sugar (glucose) in the urine, i.e., more than 1 gm. in 24 hours. [EU] Glycosyltransferases: Enzymes that catalyze the transfer of glycosyl groups to an acceptor. Most often another carbohydrate molecule acts as an acceptor, but inorganic phosphate can also act as an acceptor, such as in the case of phosphorylases. Some of the enzymes in this group also catalyze hydrolysis, which can be regarded as transfer of a glycosyl group from the donor to water. Subclasses include the hexosyltransferases, pentosyltransferases, sialyltransferases, and those transferring other glycosyl groups. EC 2.4. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a

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primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanfacine: A centrally acting antihypertensive agent. The drug lowers both systolic and diastolic blood pressure by activating the central nervous system alpha-2 adrenoreceptors, which results in reduced sympathetic outflow leading to reduced vascular tone. Its adverse reactions include dry mouth, sedation, and constipation. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]

Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] 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

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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 Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [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] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH]

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Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hexosaminidases: Enzymes that catalyze the hydrolysis of N-acylhexosamine residues in N-acylhexosamides. Hexosaminidases also act on glucosides, galactosides, and several oligosaccharides. [NIH] Hexosyltransferases: Enzymes that catalyze the transfer of hexose groups. EC 2.4.1.-. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] 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] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humeral: 1. Of, relating to, or situated in the region of the humerus: brachial. 2. Of or belonging to the shoulder. 3. Of, relating to, or being any of several body parts that are analogous in structure, function, or location to the humerus or shoulder. [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] Hydration: Combining with water. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent.

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It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [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] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral

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walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune 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] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA

Dictionary 315

synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] 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] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Instillation: . [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] 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] Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [NIH] Interferometry: Measurement of distances or movements by means of the phenomena caused by the interference of two rays of light (optical interferometry) or of sound (acoustic interferometry). [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -

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gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]

Intracranial Arteriosclerosis: Vascular diseases characterized by thickening, hardening, and remodeling of the walls of intracranial arteries. There are three subtypes: (1) atherosclerosis, marked by fatty depositions in the innermost layer of the arterial walls, (2) Monckeberg's sclerosis, which features calcium deposition in the media and (3) arteriolosclerosis, which refers to sclerosis of small caliber arteries. Clinically, this process may be associated with

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transient ischemic attack, brain infarction, intracranial embolism and thrombosis, or intracranial aneurysm. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [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] Intravesical: Within the bladder. [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] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and

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glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [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] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] 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 Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactation: The period of the secretion of milk. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [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 Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [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] Leisure Activities: Voluntary use of free time for activities outside the daily routine. [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] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] 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]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] 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] Light microscope: A microscope (device to magnify small objects) in which objects are lit

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directly by white light. [NIH] Lipid: Fat. [NIH] Lipomatosis: A disorder consisting of the accumulation of abnormal localized, or tumor-like fat in the tissues. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH]

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Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Magnesium Hydroxide: Magnesium hydroxide (Mg(OH)2). An inorganic compound that occurs in nature as the mineral brucite. It acts as an antacid with cathartic effects. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

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] Mammary: Pertaining to the mamma, or breast. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Matrilysin: The smallest member of the matrix metalloproteinases. It plays a role in tumor progression. EC 3.4.24.23. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in

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wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Assistance: Financing of medical care provided to public assistance recipients. [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] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane 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] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Meningoencephalitis: An inflammatory process involving the brain (encephalitis) and meninges (meningitis), most often produced by pathogenic organisms which invade the central nervous system, and occasionally by toxins, autoimmune disorders, and other conditions. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal

324 Cystitis

tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Menthol: An alcohol produced from mint oils or prepared synthetically. [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] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesna: A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from antineoplastic agents, such as ifosfamide or cyclophosphamide. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microscopy, Polarization: Microscopy using polarized light in which phenomena due to the preferential orientation of optical properties with respect to the vibration plane of the polarized light are made visible and correlated parameters are made measurable. [NIH] Micturition: The passage of urine; urination. [EU] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller

Dictionary 325

than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mixed Connective Tissue Disease: A syndrome with overlapping clinical features of systemic lupus erythematosus, scleroderma, polymyositis, and Raynaud's phenomenon. The disease is differentially characterized by high serum titers of antibodies to ribonucleasesensitive extractable (saline soluble) nuclear antigen and a "speckled" epidermal nuclear staining pattern on direct immunofluorescence. [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 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]

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Monocyte: A type of white blood cell. [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] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucosal Lining: The lining of GI tract organs that makes mucus. [NIH] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] 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]

Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known

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carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycobacteriosis: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neodymium: Neodymium. An element of the rare earth family of metals. It has the atomic symbol Nd, atomic number 60, and atomic weight 144.24, and is used in industrial applications. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU]

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Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [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] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] 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] 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] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH]

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Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [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] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrofurantoin: A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and longterm suppression. [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] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Nocturia: Excessive urination at night. [EU] 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

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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] Norfloxacin: Quinoline-derived synthetic antibacterial agent with a very broad spectrum of action. Oral administration yields highly bactericidal plasma, tissue, and urine levels. Norfloxacin inhibits bacterial DNA-gyrase and is used in gastrointestinal, eye, and urinary infections. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [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] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [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] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nursing Staff: Personnel who provide nursing service to patients in an organized facility, institution, or agency. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio

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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] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [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] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncogenic Viruses: Viruses that produce tumors. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the

332 Cystitis

organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] 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] Ovulation Induction: Techniques for the artifical induction of ovulation. [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] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytetracycline: An antibiotic substance isolated from the actinomycete Streptomyces rimosus and used in a wide variety of clinical conditions. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies. [NIH] Painful bladder syndrome: Another name for interstitial cystitis. [NIH]

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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] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Papovaviridae: A family of small, non-enveloped DNA viruses affecting mostly mammals. Most members can induce tumors in hosts. There are two genera: Papillomavirus and Polyomavirus. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Cells: Cells in the stomach wall that make hydrochloric acid. [NIH] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Parturition: The act or process of given birth to a child. [EU] Patella: The flat, triangular bone situated at the anterior part of the knee. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] 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 Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH]

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Patient Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pefloxacin: An orally administered broad spectrum quinolone antibacterial agent active against most gram-negative and gram-positive bacteria. It is effective against urinary tract infections as well as against many other systemic infections. The drug is well tolerated in adults, but should not be given to children and pregnant women. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentosan polysulfate: A drug used to relieve pain or discomfort associated with chronic inflammation of the bladder. It is also being evaluated for its protective effects on the gastrointestinal tract in people undergoing radiation therapy. [NIH] Pentosyltransferases: Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another. (Dorland, 28th ed) EC 2.4.2. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH]

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Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Perivascular: Situated around a vessel. [EU] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [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] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [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

336 Cystitis

the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physician Assistants: Persons academically trained, licensed, or credentialed to provide medical care under the supervision of a physician. The concept does not include nurses, but does include orthopedic assistants, surgeon's assistants, and assistants to other specialists. [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] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene

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changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Platelet Transfusion: The transfer of blood platelets from a donor to a recipient or reinfusion to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] 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]

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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 Kidney Diseases: Diseases that are characterized by the progressive expansion of a large number of tightly packed cysts within the kidney. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Chloride: Potassium chloride. A white crystal or crystalline powder used as an electrolyte replenisher, in the treatment of hypokalemia, in buffer solutions, and in fertilizers and explosives. [NIH] Potassium Citrate: A powder that dissolves in water, which is administered orally, and is used as a diuretic, expectorant, systemic alkalizer, and electrolyte replenisher. [NIH]

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Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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, 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] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary tumor: The original tumor. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH]

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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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] 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

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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] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteus: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the intestines of humans and a wide variety of animals, as well as in manure, soil, and polluted waters. Its species are pathogenic, causing urinary tract infections and are also considered secondary invaders, causing septic lesions at other sites of the body. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora,

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Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudorabies: A highly contagious herpesvirus infection affecting the central nervous system of swine, cattle, dogs, cats, rats, and other animals. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Public Assistance: Financial assistance to impoverished persons for the essentials of living through federal, state or local government programs. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyelitis: Inflammation of the pelvis of the kidney. It is attended by pain and tenderness in the loins, irritability of the bladder, remittent fever, bloody or purulent urine, diarrhoea,

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vomiting, and a peculiar pain on flexion of the thigh. [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] 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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical cystectomy: Surgery to remove the bladder as well as nearby tissues and organs. [NIH]

Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] 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] 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

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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] Rarefaction: The reduction of the density of a substance; the attenuation of a gas. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] 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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [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] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a

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straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Relapse: The return of signs and symptoms of cancer after a period of improvement. [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] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal agenesis: The absence or severe malformation of one or both kidneys. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] 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] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [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] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [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] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH]

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Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retroperitoneal Fibrosis: A slowly progressive condition of unknown etiology, characterized by deposition of fibrous tissue in the retroperitoneal space compressing the ureters, great vessels, bile duct, and other structures. When associated with abdominal aortic aneurysm, it may be called chronic periaortitis or inflammatory perianeurysmal fibrosis. [NIH]

Retroperitoneal Space: An area occupying the most posterior aspect of the abdominal cavity. It is bounded laterally by the borders of the quadratus lumborum muscles and extends from the diaphragm to the brim of the true pelvis, where it continues as the pelvic extraperitoneal space. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [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] Rod: A reception for vision, located in the retina. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saccule: The smaller of the 2 sacs within the vestibule of the ear. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] 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.

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Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] 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] Self Care: Performance of activities or tasks traditionally performed by professional health

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care providers. The concept includes care of oneself or one's family and friends. [NIH] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [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]

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Sialyltransferases: A group of enzymes with the general formula CMP-Nacetylneuraminate:acceptor N-acetylneuraminyl transferase. They catalyze the transfer of Nacetylneuraminic acid from CMP-N-acetylneuraminic acid to an acceptor, which is usually the terminal sugar residue of an oligosaccharide, a glycoprotein, or a glycolipid. EC 2.4.99.-. [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] Sitz Bath: A special plastic tub. A person sits in a few inches of warm water to help relieve discomfort of hemorrhoids or anal fissures. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [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 Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social

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support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In

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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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spices: The dried seeds, bark, root, stems, buds, leaves, or fruit of aromatic plants used to season food. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal 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] Spinous: Like a spine or thorn in shape; having spines. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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]

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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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [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] Stress urinary: Leakage of urine caused by actions--such as coughing, laughing, sneezing, running, or lifting--that place pressure on the bladder from inside the body. Stress urinary incontinence can result from either a fallen bladder or weak sphincter muscles. [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] Struvite: A type of kidney stone caused by infection. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and

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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]

Succinimides: A subclass of imides with the general structure of pyrrolidinedione. They are prepared by the distillation of ammonium succinate. They are sweet-tasting compounds that are used as chemical intermediates and plant growth stimulants. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] 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] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]

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Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachykinins: A family of biologically active peptides sharing a common conserved Cterminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [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] Tennis Elbow: A condition characterized by pain in or near the lateral humeral epicondyle or in the forearm extensor muscle mass as a result of unusual strain. It occurs in tennis players as well as housewives, artisans, and violinists. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] 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] 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] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] 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]

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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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [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] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH]

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Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] 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 Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]

Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] 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] Transcutaneous: Transdermal. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [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

Dictionary 357

earlier and stored until needed. [NIH] Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [NIH] Translating: Conversion from one language to another language. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transurethral: Performed through the urethra. [EU] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [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] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubal ligation: An operation to tie the fallopian tubes closed. This procedure prevents pregnancy by blocking the passage of eggs from the ovaries to the uterus. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor 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] 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;

358 Cystitis

called also neoplasm. [EU] Turpentine: The concrete oleoresin obtained from Pinus palustris Mill. (Pinaceae) and other species of Pinus. It contains a volatile oil, to which its properties are due, and to which form it is generally used. (Dorland, 28th ed) Turpentine is used as a solvent and an experimental irritant in biomedical research. Turpentine toxicity is of medical interest. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Ureteritis: Inflammation of the ureter. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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 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 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]

Dictionary 359

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] Urine Testing: Checking urine to see if it contains glucose (sugar) and ketones. Special strips of paper or tablets (called reagents) are put into a small amount of urine or urine plus water. Changes in the color of the strip show the amount of glucose or ketones in the urine. Urine testing is the only way to check for the presence of ketones, a sign of serious illness. However, urine testing is less desirable then blood testing for monitoring the level of glucose in the body. [NIH] 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] Urolithiasis: Stones in the urinary system. [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] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Urothelium: The epithelial lining of the urinary tract. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valganciclovir: An antiviral agent that is being studied as a treatment for AIDS-related cytomegalovirus. It is converted in the body to ganciclovir. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [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] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH]

360 Cystitis

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 blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicoureteral: An abnormal condition in which urine backs up into the ureters, and occasionally into the kidneys, raising the risk of infection. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH]

Dictionary 361

Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [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] Voiding cystourethrogram: An x-ray image of the bladder and urethra made during voiding. The bladder and urethra are filled with a special fluid to make the urethra clearly visible. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Weight Gain: Increase in body weight over existing weight. [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 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] 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 Oxide: A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock. [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]

363

INDEX 5 5-alpha, 203, 273, 305 A Abdomen, 212, 273, 284, 285, 317, 321, 335, 346, 352, 355, 361 Abdominal Cramps, 5, 273 Abdominal Pain, 174, 175, 185, 218, 250, 256, 273, 318, 335, 358 Aberrant, 86, 273 Ablate, 273, 300 Abscess, 4, 215, 273 Acceptor, 273, 309, 349 Acetone, 141, 144, 273, 319 Acetylcholine, 273, 290, 329 Acetylgalactosamine, 273, 308 Acetylglucosamine, 60, 273, 308 Acne, 180, 273 Acoustic, 273, 316, 360 Acremonium, 273, 289 Actin, 84, 273 Activities of Daily Living, 26, 247, 273 Acute lymphoblastic leukemia, 149, 273 Acute lymphocytic leukemia, 273 Acute renal, 273, 274, 311 Acute tubular, 45, 274 Adaptability, 274, 288, 289 Adaptation, 68, 76, 274, 336 Adenine, 274 Adenocarcinoma, 109, 274 Adenosine, 98, 132, 194, 274, 286, 335 Adenosine Triphosphate, 98, 132, 274, 335 Adenovirus, 70, 94, 97, 102, 112, 137, 142, 274 Adenylate Cyclase, 74, 274 Adhesions, 69, 274 Adjustment, 40, 274 Adjuvant, 66, 198, 274, 307 Adjuvant Therapy, 66, 274 Adolescence, 3, 274 Adoptive Transfer, 42, 68, 274 Adrenal Cortex, 274, 295, 303, 331, 339 Adrenal Medulla, 274, 287, 303, 329 Adrenergic, 72, 82, 121, 192, 194, 274, 277, 299, 303, 353 Adverse Effect, 6, 13, 20, 141, 215, 275, 349 Aerobic, 174, 275, 325 Aeroembolism, 275, 283 Aerosol, 179, 275

Aetiology, 89, 116, 275 Afferent, 37, 38, 49, 52, 54, 71, 74, 78, 79, 81, 85, 275 Affinity, 80, 83, 99, 275, 281, 321, 350 Agar, 275, 295 Age Groups, 30, 275 Aged, 80 and Over, 275 Agenesis, 275 Aggravation, 38, 275 Agonist, 37, 177, 201, 275, 299, 327 Airways, 177, 275 Alanine, 51, 275 Albumin, 275, 332, 336 Alertness, 276, 286 Algorithms, 13, 63, 276, 284 Alimentary, 276, 333 Alkaline, 181, 209, 210, 276, 277, 286 Alkaloid, 276, 283, 286, 326 Alkylate, 45, 276 Alkylating Agents, 276, 354 Alleles, 55, 276 Allergen, 276, 348 Allergic Rhinitis, 199, 276, 289 Allogeneic, 114, 133, 136, 153, 276, 309, 311 Allogeneic bone marrow transplantation, 133, 136, 153, 276 Aloe, 251, 276 Alopecia, 276, 296 Alpha Particles, 276, 343 Alpha-1, 276, 277 Alternative medicine, 223, 276 Alum, 140, 276 Aluminum, 140, 276 Ameliorated, 36, 277 Amine, 277, 312 Amino Acid Sequence, 77, 277, 279, 307 Amino Acids, 51, 195, 277, 296, 307, 328, 334, 338, 341, 346, 353, 357, 358 Amitriptyline, 13, 64, 224, 277 Ammonia, 277, 309, 358 Amoxicillin, 27, 277 Ampicillin, 277 Amplification, 96, 104, 277 Ampulla, 277, 301, 304 Amyloid, 131, 277, 289 Anaemia, 210, 277 Anaerobic, 137, 174, 196, 277, 341

364 Cystitis

Anaesthesia, 277, 315 Anal, 277, 298, 302, 305, 349 Anal Fissure, 277, 349 Analgesic, 187, 278, 301, 326, 331 Analogous, 24, 278, 312, 337, 356 Analytes, 242, 243, 278 Anaphylactic, 278, 337 Anaphylatoxins, 278, 293 Anaphylaxis, 173, 192, 278 Anaplasia, 278, 328 Anatomical, 11, 184, 196, 248, 257, 278, 285, 315, 347 Anemia, 278, 326 Anesthesia, 4, 5, 10, 11, 32, 63, 119, 175, 192, 206, 245, 249, 278, 295, 339 Anesthetics, 12, 278, 303 Angiogenesis, 90, 278, 323 Angiography, 109, 278 Angiopathy, 278, 289 Animal model, 56, 60, 68, 71, 73, 85, 88, 92, 278 Anionic, 60, 278 Anions, 276, 278, 318 Annealing, 278, 338 Anomalies, 4, 279, 326, 354 Anorexia, 35, 279 Antagonism, 279, 286, 298, 299 Antibacterial, 6, 20, 27, 171, 178, 279, 308, 330, 331, 334, 351 Antibodies, 49, 80, 86, 191, 195, 197, 199, 200, 279, 280, 281, 310, 312, 314, 322, 325, 336, 343 Antibody, 58, 86, 179, 200, 275, 279, 292, 303, 310, 312, 313, 314, 315, 323, 325, 343, 348, 351 Anticholinergic, 277, 279, 289, 299 Anticoagulant, 279, 341 Antidepressant, 176, 206, 277, 279 Antiemetic, 279, 313 Antifungal, 279, 308, 319 Antigen-Antibody Complex, 279, 292 Antihypertensive, 279, 310 Anti-infective, 279, 329 Anti-inflammatory, 89, 173, 187, 193, 279, 295, 308, 336 Anti-Inflammatory Agents, 193, 279, 295 Antineoplastic, 276, 279, 284, 295, 296, 299, 324, 325, 337, 360 Antineoplastic Agents, 276, 279, 324, 360 Antioxidant, 280, 281 Antiproliferative, 20, 36, 39, 88, 97, 100, 125, 131, 152, 170, 191, 222, 280

Antiseptic, 273, 280, 361 Antiserum, 83, 280 Antispasmodic, 196, 280, 331 Antiviral, 280, 317, 334, 359 Anus, 250, 277, 280, 285, 334, 344 Anxiety, 193, 194, 280, 313 Aortic Aneurysm, 280, 346 Aplasia, 216, 280 Apolipoproteins, 280, 321 Aponeurosis, 280, 307 Apoptosis, 58, 84, 100, 280 Aqueous, 173, 187, 280, 282, 296, 320 Arachidonic Acid, 60, 280, 300, 320, 340 Arginine, 8, 67, 72, 106, 128, 140, 141, 159, 175, 201, 202, 222, 278, 280, 296, 329, 332 Aromatic, 280, 351, 354 Arrhythmia, 280, 360 Arterial, 107, 280, 281, 289, 290, 313, 317, 341, 354 Arteries, 278, 280, 284, 285, 294, 317, 321, 324, 355 Arteriolar, 280, 285 Arterioles, 280, 285, 286 Arteriovenous, 281, 289 Arthralgia, 187, 281 Arthritis, Rheumatoid, 187, 281 Articular, 281, 332 Ascites, 281, 331 Ascorbic Acid, 192, 281, 313 Aseptic, 281, 331, 351 Aspartate, 81, 281 Aspiration, 210, 281 Assay, 96, 281, 314 Astringent, 281, 361 Astrocytes, 76, 281 Asymptomatic, 4, 9, 16, 24, 29, 32, 33, 55, 57, 68, 76, 88, 136, 166, 181, 190, 201, 213, 215, 281 Atmospheric Pressure, 275, 281, 313 Atopic, 59, 199, 281 Atrophy, 281 Attenuated, 281, 298 Attenuation, 77, 281, 344 Atypical, 30, 281 Autoantibodies, 27, 59, 135, 185, 281 Autoantigens, 281 Autoimmune disease, 41, 185, 281, 282, 326 Autoimmunity, 27, 282 Autologous, 70, 282, 311 Autologous bone marrow transplantation, 282, 311

Index 365

Autonomic, 74, 273, 282, 329, 335, 353 Autonomic Nervous System, 282, 335, 353 Autopsy, 210, 282 Axons, 50, 282, 328, 331, 339 B Bacillus, 41, 59, 106, 117, 129, 173, 224, 282 Back Pain, 256, 282 Bacterial Infections, 6, 68, 172, 197, 218, 282, 289 Bacterial Physiology, 274, 282 Bacterial toxin, 84, 282 Bactericidal, 178, 282, 330 Bacteriophage, 282, 356, 360 Bacterium, 83, 282, 311 Basal Ganglia, 282, 289, 307 Basement Membrane, 282, 287, 304 Basophil, 283, 312 Bends, 179, 283 Benign, 30, 34, 72, 98, 156, 166, 184, 187, 195, 196, 203, 216, 283, 305, 307, 310, 328, 343 Benign prostatic hyperplasia, 34, 184, 203, 283, 305 Benzene, 283 Benzodiazepines, 194, 283 Berberine, 142, 283 Beta-pleated, 277, 283 Beta-Thromboglobulin, 283, 317 Bifida, 283 Bilateral, 122, 283 Bile, 283, 306, 321, 346, 351 Biliary, 283, 286 Biliary Tract, 283, 286 Binding Sites, 60, 283 Biochemical, 41, 53, 60, 62, 84, 175, 276, 283, 284, 306, 320, 332, 348 Biological Markers, 27, 39, 79, 80, 283 Biological response modifier, 283, 284, 316 Biological therapy, 284, 310 Biological Transport, 284, 298 Bioluminescence, 54, 284 Biomarkers, 89, 284 Biopsy, 4, 5, 7, 11, 20, 25, 38, 50, 63, 72, 98, 170, 175, 184, 206, 219, 284, 334 Biopsy specimen, 25, 38, 50, 184, 284 Bioreactors, 54, 284 Biosynthesis, 60, 280, 284, 308, 335 Biotechnology, 92, 95, 209, 223, 237, 284 Bleomycin, 149, 284 Blepharitis, 173, 284 Blind spot, 5, 284 Bloating, 176, 193, 284, 315, 318

Blood Coagulation, 284, 286, 355 Blood Platelets, 284, 337, 348, 355 Blood pressure, 270, 274, 279, 284, 313, 325, 350 Body Fluids, 284, 285, 299, 350, 357 Body Regions, 285, 292 Bone scan, 285, 347 Bowel, 11, 22, 177, 196, 270, 273, 277, 285, 298, 302, 316, 317, 335, 352, 358 Bowel Movement, 285, 298, 352 Brachytherapy, 285, 317, 343 Bradykinin, 188, 285, 318, 329, 336 Branch, 267, 285, 322, 333, 342, 350, 353, 355 Breakdown, 77, 285, 298, 307 Broad-spectrum, 277, 285, 289, 331 Bronchi, 285, 303, 304 Bronchial, 45, 177, 285, 312 Bronchitis, 45, 180, 285, 290 Bronchoconstriction, 177, 285, 337 Bronchus, 285 Buccal, 179, 285, 321 Bupivacaine, 285, 320 Burns, 179, 285 Burns, Electric, 285 C Caffeine, 228, 250, 271, 285 Calcitonin Gene-Related Peptide, 59, 286 Calcium, 13, 46, 140, 182, 184, 186, 194, 195, 251, 286, 292, 298, 317, 322, 332, 349, 360 Calcium Carbonate, 251, 286 Calcium channel blocker, 13, 184, 194, 286, 360 Calcium Channel Blockers, 13, 184, 194, 286 Calculi, 24, 107, 208, 286, 358 Calendula, 160, 173, 286 Canonical, 80, 286 Capillary, 285, 286, 346, 360 Capillary Permeability, 285, 286 Capsaicin, 37, 38, 83, 140, 202, 286 Carbapenems, 16, 287 Carbohydrate, 43, 287, 295, 309, 338 Carboprost, 142, 287 Carboxy, 187, 287 Carcinoembryonic Antigen, 137, 287 Carcinogenesis, 183, 287, 336 Carcinogenic, 276, 283, 287, 316, 331, 340, 351 Carcinogens, 83, 182, 287, 327

366 Cystitis

Carcinoma, 12, 19, 42, 72, 124, 184, 216, 287 Carcinoma in Situ, 12, 19, 72, 287 Cardiac, 180, 286, 287, 300, 303, 304, 320, 327, 351 Cardiovascular, 287, 320, 348, 354 Carotenoids, 286, 287 Carrier Proteins, 287, 336 Case report, 107, 110, 113, 118, 125, 142, 287, 291 Case series, 287, 291 Catecholamine, 192, 287, 299, 335 Catheterization, 176, 190, 255, 287, 318 Catheters, 166, 190, 219, 287, 315, 317 Cations, 288, 318 Caudal, 288, 298, 313, 338 Causal, 288, 302 Caveolae, 76, 288 Caveolins, 288 Cecum, 288, 319 Cell, 14, 18, 20, 25, 30, 35, 37, 38, 41, 43, 45, 46, 48, 49, 51, 52, 54, 58, 59, 60, 67, 70, 72, 76, 77, 78, 79, 82, 83, 84, 85, 86, 88, 89, 90, 99, 100, 109, 113, 120, 133, 170, 173, 174, 177, 179, 191, 197, 199, 200, 201, 216, 222, 273, 275, 278, 280, 281, 282, 283, 284, 286, 287, 288, 289, 290, 291, 293, 295, 296, 297, 301, 302, 303, 304, 306, 307, 308, 310, 312, 314, 315, 316, 317, 319, 320, 323, 325, 326, 327, 328, 330, 332, 335, 336, 337, 340, 344, 345, 347, 349, 350, 352, 353, 355, 356, 357, 359, 361 Cell Adhesion, 54, 288 Cell Communication, 67, 288 Cell Count, 25, 120, 288 Cell Cycle, 90, 288, 291, 303 Cell Death, 84, 280, 288, 303, 327 Cell Differentiation, 77, 288, 349 Cell Division, 282, 288, 303, 310, 323, 325, 336, 340, 347, 350 Cell Lineage, 82, 288 Cell membrane, 77, 284, 286, 287, 288, 304, 307, 335 Cell Membrane Structures, 288 Cell Physiology, 88, 288 Cell proliferation, 88, 170, 191, 201, 288, 317, 349 Cell Respiration, 288, 325, 345 Cell Size, 288, 306 Cell Survival, 289, 310 Cell Transplantation, 133, 289

Central Nervous System Infections, 289, 310 Cephalexin, 27, 289 Cephaloridine, 289 Cephalosporins, 16, 33, 289 Cephalothin, 289 Cerebral, 37, 76, 190, 282, 289, 303, 304, 305, 306, 333, 350, 355 Cerebral Hemorrhage, 190, 289 Cerebral Infarction, 289 Cerebral Palsy, 289, 350 Cerebrovascular, 286, 289 Cerebrum, 289 Cervical, 187, 195, 289 Cervix, 289, 306, 345 Cetirizine, 289, 313 Character, 290, 297 Checkup, 212, 290 Chemokines, 195, 290 Chemotactic Factors, 174, 290, 293 Chemotherapy, 35, 100, 113, 142, 149, 183, 272, 274, 290 Chest Pain, 5, 176, 290 Chlamydia, 250, 290 Cholesterol, 283, 288, 290, 321, 351 Cholesterol Esters, 290, 321 Cholinergic, 72, 82, 194, 277, 290 Chondroitin sulfate, 133, 140, 143, 189, 290 Chromatin, 280, 290, 330 Chromosomal, 68, 277, 290, 346 Chromosome, 69, 290, 347 Chronic Disease, 12, 15, 34, 76, 174, 197, 290, 320 Chronic Obstructive Pulmonary Disease, 192, 290 Chronic prostatitis, 30, 34, 43, 46, 47, 48, 51, 63, 66, 203, 215, 249, 290 Chronic renal, 185, 290, 338 Chylomicrons, 290, 321 Chymopapain, 290, 333 Cicatrix, 290, 319 Cimetidine, 19, 222, 290 Ciprofloxacin, 27, 33, 291 Cisplatin, 149, 291 Citrus, 250, 281, 291 Clear cell carcinoma, 291, 297 Clinical Medicine, 115, 291, 339 Clinical Protocols, 43, 63, 291 Clinical series, 10, 291 Clinical study, 291, 294

Index 367

Clinical trial, 35, 39, 42, 43, 47, 48, 50, 59, 61, 62, 63, 64, 65, 66, 67, 82, 96, 126, 127, 165, 167, 237, 291, 294, 296, 326, 341, 344 Clone, 88, 291 Cloning, 69, 284, 291 Cluster Analysis, 80, 291 Coagulation, 284, 291, 311, 320, 336, 355 Cochlear, 291, 356, 360 Cochlear Diseases, 291, 356 Coenzyme, 281, 291 Cofactor, 292, 341, 355 Cohort Studies, 292, 302 Colic, 192, 208, 292 Colitis, 292, 318 Collagen, 111, 281, 283, 292, 304, 305, 307, 319, 322, 337, 340, 350 Collapse, 278, 285, 292 Colloidal, 275, 292, 300 Colorectal, 137, 292 Colorectal Cancer, 137, 292 Combination Therapy, 42, 189, 292 Communis, 162, 292 Compassionate, 206, 208, 213, 248, 292 Complement, 46, 143, 192, 195, 278, 292, 293, 307, 322, 336, 348 Complementary and alternative medicine, 147, 164, 293 Complementary medicine, 147, 293 Complete remission, 293, 345 Computational Biology, 237, 293 Computed tomography, 293, 347 Computerized axial tomography, 293, 347 Conception, 293, 294, 305, 351 Concretion, 286, 293 Conduction, 179, 293, 354 Congestion, 5, 293, 303 Congestive heart failure, 192, 293 Conjugated, 60, 293, 296, 346 Conjunctiva, 293, 319 Conjunctivitis, 173, 293 Connective Tissue, 121, 185, 281, 285, 292, 293, 294, 305, 307, 310, 319, 321, 324, 346, 354 Connective Tissue Cells, 294 Consciousness, 278, 294, 298 Constipation, 196, 210, 248, 252, 294, 306, 310, 318, 335 Constitutional, 294, 327 Constriction, 294, 318 Contamination, 180, 294 Contraceptive, 55, 294 Contractility, 70, 294

Contracture, 104, 294 Contraindications, ii, 252, 294 Control group, 5, 24, 56, 294, 343 Controlled clinical trial, 47, 48, 50, 63, 64, 65, 67, 167, 294 Controlled study, 5, 102, 294 Conventional therapy, 294 Conventional treatment, 218, 294 Cooperative group, 46, 294 Coordination, 67, 294, 326 Cornea, 294, 309, 319, 352 Corneum, 294, 303 Coronary, 186, 294, 324 Coronary Thrombosis, 294, 324 Corpus, 295, 334, 339, 355 Corpus Luteum, 295, 339 Cortex, 295, 304, 305 Cortical, 46, 295 Corticosteroid, 295, 339 Cortisol, 105, 128, 276, 295 Cranial, 295, 310, 318, 331, 335, 360 Craniocerebral Trauma, 289, 295, 310, 356 Creatine, 59, 295 Creatinine, 25, 295 Cromolyn Sodium, 173, 189, 295 Cross-Sectional Studies, 295, 302 Culture Media, 39, 275, 295 Cultured cells, 44, 54, 295 Curare, 295, 326 Curative, 15, 190, 207, 296, 355 Cutaneous, 296, 318, 321, 333 Cyclic, 24, 72, 87, 193, 274, 286, 288, 296, 310, 329, 335, 340 Cyclosporine, 113, 296 Cyst, 210, 296 Cystectomy, 19, 27, 29, 81, 132, 133, 198, 296 Cysteine, 290, 296, 353 Cystine, 296, 358 Cystinuria, 216, 296 Cystometrogram, 12, 25, 296 Cystoscopy, 4, 5, 7, 11, 13, 14, 17, 21, 36, 170, 174, 219, 224, 242, 245, 249, 256, 271, 296 Cytochrome, 291, 296 Cytokine, 44, 59, 72, 75, 84, 122, 126, 296, 317 Cytomegalovirus, 103, 296, 307, 359 Cytoplasm, 280, 288, 296, 297, 302, 310, 346 Cytoprotection, 78, 296 Cytoskeleton, 54, 78, 297

368 Cystitis

Cytotoxic, 84, 286, 297, 314, 343, 349 Cytotoxicity, 291, 297 D Dairy Products, 247, 297 Data Collection, 50, 297 Databases, Bibliographic, 237, 297 Daunorubicin, 297, 299 Deamination, 297, 358 Decarboxylation, 297, 312 Decubitus, 179, 297, 358 Decubitus Ulcer, 179, 297 Defense Mechanisms, 6, 21, 34, 178, 297 Degenerative, 187, 297, 332 Deletion, 68, 280, 297 Delivery of Health Care, 248, 297, 311 Denaturation, 297, 338 Dendrites, 297, 328 Density, 20, 25, 37, 68, 76, 297, 306, 321, 331, 344, 350 Dermatitis, 59, 152, 177, 180, 199, 297, 300, 313 DES, 80, 278, 297 Diabetes Mellitus, 4, 119, 185, 298, 308 Diagnostic procedure, 169, 206, 223, 298 Diaphragm, 28, 222, 250, 298, 337, 346 Diarrhea, 176, 196, 298, 306, 318, 319 Diarrhoea, 298, 342 Diastolic, 298, 310, 313 Diastolic blood pressure, 298, 310 Diencephalon, 298, 313, 355 Diffusion, 8, 284, 286, 298, 316 Digestion, 56, 276, 283, 285, 298, 300, 315, 317, 321, 352, 359 Digestive system, 168, 298, 326 Dihydrotestosterone, 203, 273, 298, 344 Dilation, 177, 285, 298 Dilator, 194, 298 Diltiazem, 184, 298 Dilution, 218, 298 Dimethyl, 7, 11, 21, 23, 30, 106, 135, 173, 174, 189, 206, 224, 228, 298 Direct, iii, 38, 53, 70, 74, 76, 83, 89, 178, 185, 197, 227, 288, 291, 298, 299, 325, 344 Discriminant Analysis, 80, 298 Dissociation, 275, 298, 318 Distal, 71, 180, 298, 300, 335, 339, 342 Distention, 13, 28, 32, 63, 66, 75, 87, 173, 174, 218, 245, 249, 299 Diuresis, 286, 299 Diuretic, 299, 338 Diverticula, 11, 299 Diverticulum, 110, 299

Dizziness, 5, 299, 360 Domesticated, 299, 310 Dopamine, 193, 299 Dopamine Agonists, 193, 299 Dorsal, 74, 299, 338, 351 Dorsum, 299, 307 Dose-dependent, 179, 299 Dose-limiting, 49, 299 Doxepin, 106, 299 Doxorubicin, 30, 189, 299 Doxycycline, 74, 228, 299 Drive, ii, vi, 9, 11, 14, 27, 29, 30, 59, 139, 185, 214, 252, 253, 299 Drug Interactions, 215, 229, 230, 299 Duct, 277, 287, 299, 304, 346 Duodenum, 283, 299, 301, 329, 352 Dyes, 277, 300, 306, 329 Dysmenorrhea, 193, 300, 336 Dyspareunia, 7, 12, 14, 21, 30, 32, 194, 300 Dyspepsia, 300, 315 Dystrophy, 27, 150, 300 Dysuria, 12, 21, 23, 33, 186, 188, 190, 202, 214, 218, 270, 300 E Eczema, 173, 180, 300 Edema, 59, 156, 184, 300, 318, 326, 331 Effector, 273, 292, 300, 329, 335 Eicosanoids, 79, 300 Elasticity, 190, 300 Elastin, 292, 300, 304 Electrocoagulation, 26, 291, 300 Electrode, 198, 300 Electrolysis, 210, 278, 288, 300 Electrolyte, 295, 300, 338, 350 Electron microscope, 185, 300 Electrons, 280, 282, 300, 318, 343 Electrophoresis, 80, 300 Embolism, 107, 300, 318 Embryo, 288, 301, 315, 331, 337 Emodin, 276, 301 Emollient, 301, 331 Emphysema, 290, 301 Empiric, 13, 29, 30, 31, 38, 60, 61, 170, 301 Empirical, 6, 24, 107, 134, 185, 189, 212, 301 Encephalitis, 114, 301, 323 Encephalitis, Viral, 301 Encephalomyelitis, 185, 301 Endemic, 301, 351 Endocrine System, 301, 328 Endocrinology, 301, 310 Endocytosis, 53, 288, 301

Index 369

Endometrial, 301 Endometriosis, 18, 133, 301 Endometrium, 301, 323 Endorphin, 188, 301 Endoscope, 301 Endoscopic, 10, 31, 72, 131, 248, 296, 301 Endoscopy, 73, 301 Endothelial cell, 78, 90, 124, 301, 317, 355 Endothelium, 45, 79, 90, 302, 329 Endothelium, Lymphatic, 302 Endothelium, Vascular, 302 Endothelium-derived, 302, 329 Endotoxin, 67, 302, 357 End-stage renal, 290, 302, 338 Enkephalin, 188, 302 Enteritis, 100, 302 Enterocolitis, 302 Environmental Exposure, 283, 302 Environmental Health, 236, 238, 302 Enzymatic, 72, 180, 286, 293, 302, 312, 333, 338 Enzyme Inhibitors, 302, 336 Eosinophil, 20, 302 Eosinophilia, 130, 302 Eosinophilic, 19, 97, 102, 104, 108, 130, 141, 302 Epidemic, 302, 351 Epidemiologic Factors, 20, 302 Epidemiologic Studies, 23, 283, 302 Epidemiological, 5, 8, 26, 34, 57, 74, 84, 303 Epidermal, 24, 87, 88, 97, 99, 100, 131, 201, 303, 319, 323, 325 Epidermal Growth Factor, 24, 87, 88, 97, 99, 100, 131, 201, 303 Epidermis, 180, 294, 303, 312, 319, 342 Epinephrine, 274, 299, 303, 329, 358 Epithelial Cells, 30, 34, 40, 45, 46, 54, 58, 76, 77, 85, 88, 99, 103, 172, 174, 182, 201, 303 Epithelium, 14, 27, 30, 34, 43, 45, 52, 54, 60, 76, 78, 82, 88, 170, 182, 201, 282, 302, 303 Epitope, 51, 200, 303 Erectile, 303, 334 Erythema, 303, 359 Erythrocytes, 277, 278, 285, 303, 308, 344, 348 Esophagus, 298, 303, 311, 344, 352 Estradiol, 83, 303 Estrogen, 16, 57, 73, 83, 141, 194, 303 Estrogen receptor, 83, 303

Etoposide, 149, 303 Eukaryotic Cells, 178, 303, 315, 330, 332 Evacuation, 26, 294, 303 Evoke, 304, 352 Excitability, 37, 85, 304, 327, 328 Excitation, 304, 306 Exfoliation, 34, 100, 304 Exocrine, 177, 304, 333 Exocytosis, 53, 54, 304, 312 Exogenous, 41, 300, 304 Expectorant, 304, 338 Extensor, 304, 342, 354 External-beam radiation, 304, 343 Extracellular, 54, 77, 120, 277, 281, 294, 301, 304, 305, 322, 350 Extracellular Matrix, 294, 304, 305, 322 Extracellular Matrix Proteins, 304, 322 Extrapyramidal, 299, 304 Extravasation, 59, 83, 109, 304 Eye Infections, 274, 304 F Fallopian Tubes, 304, 345, 357 Family Planning, 237, 304 Fat, 278, 280, 285, 295, 297, 304, 319, 321, 326, 346, 350 Fatigue, 26, 270, 304, 311 Fatty acids, 276, 300, 305, 340, 355 Febrile, 258, 305 Fecal Incontinence, 198, 305, 315 Feces, 69, 287, 294, 305, 352 Fertilizers, 305, 329, 338 Fetus, 29, 305, 306, 336, 359 Fibrin, 284, 305, 335, 355, 358 Fibrinogen, 305, 336, 355 Fibroblasts, 90, 294, 305, 317, 350 Fibrosis, 45, 90, 184, 216, 294, 305, 346, 347 Finasteride, 203, 305 Fissure, 292, 305 Fistula, 110, 210, 305 Fixation, 305, 348 Flank Pain, 29, 187, 305 Flatus, 305, 307 Flexion, 306, 343 Flow Cytometry, 89, 306 Fluorescence, 54, 88, 306 Fluorescent Dyes, 306 Foetoplacental, 306, 331 Follicular Phase, 75, 306 Foramen, 292, 306, 335 Forearm, 284, 306, 354 Fosfomycin, 17, 110, 228, 306 Fourth Ventricle, 306, 321, 355

370 Cystitis

Functional Disorders, 91, 306 Fungi, 279, 284, 304, 306, 324, 361 Fungicide, 46, 306 Fungus, 289, 306 G Gallbladder, 273, 283, 298, 306 Gamma Rays, 307, 343 Ganciclovir, 307, 359 Ganglia, 49, 74, 273, 307, 328, 335, 353 Ganglion, 49, 307, 331, 360 Gap Junctions, 307, 353 Gas, 275, 277, 283, 298, 305, 306, 307, 313, 315, 318, 326, 329, 344, 360 Gastric, 111, 177, 277, 291, 303, 307, 311, 312, 313, 334 Gastric Acid, 177, 277, 291, 307 Gastrin, 291, 307, 312 Gastritis, 4, 187, 307 Gastrointestinal tract, 178, 287, 307, 319, 320, 334, 348, 357 Gelatin, 295, 307, 355 Gene, 42, 55, 56, 57, 70, 82, 83, 86, 88, 90, 93, 100, 209, 211, 274, 276, 283, 284, 286, 307, 336, 347 Gene Expression, 55, 57, 82, 86, 90, 100, 211, 307 Generator, 81, 307 Genes, Bacterial, 77, 307 Genetic Code, 307, 330 Genetic Engineering, 284, 291, 307 Genetic testing, 308, 338 Genetics, 56, 69, 308 Genital, 196, 209, 251, 291, 308, 310, 359, 361 Genitourinary, 47, 178, 197, 308, 354, 359 Genomics, 54, 100, 308 Genotype, 308, 335 Gentian Violet, 113, 308 Geriatric, 33, 308 Germ Cells, 308, 323, 332, 350, 354 Gland, 195, 274, 295, 308, 321, 322, 333, 340, 341, 347, 352 Glial Fibrillary Acidic Protein, 76, 308 Globosides, 172, 308 Glomerular, 90, 308, 345 Glomeruli, 308, 343 Glomerulus, 308, 328 Glucocorticoid, 308, 339 Glucose, 281, 298, 308, 309, 316, 346, 359 Glucose Intolerance, 298, 308 Glucuronic Acid, 308, 311 Glutamate, 81, 308, 309

Glutamic Acid, 309, 340 Glutamine, 84, 309 Glycerophosphates, 195, 309 Glycogen, 290, 309 Glycolysis, 196, 309 Glycoprotein, 20, 39, 87, 287, 305, 309, 349, 355, 357 Glycosaminoglycan, 27, 38, 56, 182, 290, 309 Glycosuria, 216, 309 Glycosyltransferases, 44, 309 Goats, 297, 309 Gonad, 309 Gonadal, 74, 309, 351 Gonorrhea, 178, 250, 309 Governing Board, 309, 339 Gp120, 309, 334 Grade, 183, 309 Graft, 309, 312, 315 Graft Rejection, 309, 315 Grafting, 82, 309, 315 Gram-negative, 20, 55, 289, 290, 309, 329, 331, 334, 341 Gram-positive, 40, 55, 289, 310, 319, 329, 331, 334, 352 Granulation Tissue, 25, 310 Granulocytes, 283, 310, 320, 349, 361 Gravis, 185, 192, 310 Growth factors, 81, 88, 90, 310, 316 Guanfacine, 37, 310 Guanylate Cyclase, 310, 329 Guinea Pigs, 78, 142, 152, 310 Gynecology, 44, 51, 66, 95, 104, 112, 125, 134, 190, 310 Gyrase, 310, 330 H Haematoma, 310 Haemorrhage, 117, 310 Hair follicles, 310, 361 Half-Life, 310, 336 Haptens, 275, 310 Headache, 5, 176, 193, 286, 310, 311, 339 Headache Disorders, 311 Health Care Costs, 76, 311 Health Education, 130, 311 Health Expenditures, 311 Health Services, 40, 297, 311 Heart failure, 311, 331 Heartburn, 311, 315 Hematopoietic Stem Cell Transplantation, 114, 118, 311 Hematuria, 8, 29, 131, 216, 242, 270, 311

Index 371

Hemodialysis, 286, 311 Hemolytic, 216, 311 Hemorrhage, 25, 192, 295, 300, 310, 311, 342, 352 Hemorrhoids, 180, 311, 349 Hemostasis, 26, 311, 348 Hepatic, 216, 276, 311 Heredity, 307, 308, 312 Heterogeneity, 275, 312 Hexosaminidases, 308, 312 Hexosyltransferases, 309, 312 Histamine, 83, 173, 176, 177, 184, 278, 289, 290, 299, 312, 313 Histamine Release, 176, 177, 278, 312 Histidine, 312 Histology, 11, 312 Homogeneous, 17, 312 Homologous, 93, 94, 111, 276, 312, 316, 347, 348, 353 Hormonal, 74, 75, 193, 202, 224, 260, 281, 295, 312 Hormone, 28, 83, 274, 283, 295, 297, 300, 303, 307, 312, 316, 323, 332, 339, 346, 349, 354 Hormone therapy, 274, 312 Horny layer, 303, 312 Humeral, 312, 354 Hybrid, 291, 312 Hybridization, 55, 76, 312 Hybridomas, 312, 317 Hydration, 35, 312 Hydrochloric Acid, 312, 333 Hydrogen, 273, 277, 282, 287, 297, 304, 313, 325, 329, 330, 341 Hydrolysis, 291, 309, 312, 313, 338, 341 Hydrophilic, 51, 182, 313 Hydrophobic, 313, 321 Hydroxylysine, 292, 313 Hydroxyproline, 292, 313 Hydroxyzine, 8, 96, 114, 175, 224, 313 Hyperaemia, 293, 313 Hyperalgesia, 60, 313 Hyperbaric, 114, 115, 120, 124, 133, 135, 149, 150, 151, 152, 153, 313 Hyperbaric oxygen, 114, 115, 120, 124, 133, 135, 149, 150, 151, 152, 153, 313 Hyperplasia, 187, 313 Hypersensitivity, 18, 52, 60, 81, 99, 202, 276, 278, 302, 313, 320, 346, 348 Hypersensitivity, Immediate, 313 Hypertension, 186, 192, 286, 289, 313, 318 Hypertrophy, 196, 202, 283, 313

Hypotension, 192, 313, 329, 337 Hypothalamic, 83, 313 Hypothalamus, 83, 282, 298, 302, 313, 329, 355 Hypoxia, 90, 314 Hysterectomy, 18, 26, 314 I Id, 144, 155, 183, 242, 243, 257, 258, 266, 268, 314 Idiopathic, 17, 18, 20, 115, 118, 184, 314 Ifosfamide, 49, 314, 324 Ileal, 238, 314 Ileum, 288, 314, 329 Immune adjuvant, 276, 314 Immune function, 224, 314 Immune response, 198, 200, 274, 276, 279, 281, 295, 309, 310, 314, 315, 322, 348, 353, 361 Immune Sera, 314 Immune system, 59, 62, 172, 185, 282, 284, 314, 315, 320, 322, 326, 359, 361 Immunity, 42, 58, 111, 172, 275, 314, 356 Immunization, 190, 274, 314, 315, 348 Immunoassay, 89, 102, 314 Immunofluorescence, 314, 325 Immunogen, 200, 314 Immunogenic, 185, 200, 314 Immunoglobulin, 45, 94, 179, 279, 314, 325 Immunohistochemistry, 76, 314 Immunologic, 42, 74, 92, 274, 290, 314, 343 Immunology, 69, 90, 91, 124, 274, 275, 306, 314 Immunosuppressive, 13, 185, 296, 308, 314, 315 Immunosuppressive Agents, 13, 314 Immunosuppressive therapy, 315 Immunotherapy, 198, 274, 284, 315 Impairment, 91, 203, 304, 315, 324 Implant radiation, 315, 317, 343 Implantation, 9, 11, 293, 315, 331 In situ, 54, 69, 76, 78, 89, 315 In Situ Hybridization, 54, 315 In vitro, 6, 37, 46, 49, 54, 57, 58, 72, 81, 88, 89, 96, 103, 177, 178, 179, 315, 338, 356 In vivo, 46, 48, 49, 52, 58, 69, 72, 74, 77, 81, 83, 88, 179, 311, 315, 355 Incision, 315, 318, 358 Incontinence, 26, 70, 78, 157, 188, 190, 198, 202, 206, 208, 209, 212, 213, 252, 255, 270, 315, 352 Indicative, 171, 207, 315, 333, 359 Indigestion, 210, 315, 319

372 Cystitis

Induction, 42, 60, 72, 75, 142, 315, 332 Infancy, 180, 211, 315 Infant, Newborn, 275, 315 Infarction, 283, 289, 294, 315, 318, 324 Infertility, 194, 316, 359 Infiltration, 18, 199, 316, 339 Inflammatory bowel disease, 196, 316 Infusion, 35, 316, 356 Ingestion, 149, 316, 337 Inhalation, 275, 316, 337 Initiation, 58, 65, 72, 188, 316 Innervation, 71, 81, 184, 299, 316, 347, 355 Inorganic, 291, 309, 316, 322, 326, 329 Inotropic, 299, 316 Insight, 39, 41, 56, 69, 76, 316 Insomnia, 176, 193, 316, 339 Instillation, 7, 14, 24, 32, 42, 63, 113, 117, 142, 165, 189, 206, 218, 224, 254, 316 Insulator, 316, 326 Insulin, 24, 87, 185, 316, 319, 350 Insulin-dependent diabetes mellitus, 316 Insulin-like, 24, 87, 316, 350 Insulin-Like Growth Factor Binding Protein 3, 87, 316 Intercellular Junctions, 45, 316 Interferometry, 72, 316 Interferon, 56, 66, 76, 316, 317, 322 Interferon-alpha, 66, 316, 317 Interleukin-2, 59, 317 Interleukin-4, 121, 317 Interleukin-6, 59, 83, 87, 317 Interleukin-8, 87, 317 Interleukins, 315, 317 Intermittent, 7, 11, 317, 321 Internal Medicine, 5, 47, 134, 143, 190, 301, 317 Internal radiation, 317, 343 Intestinal, 107, 109, 177, 195, 196, 302, 317, 319 Intestine, 285, 292, 302, 317, 319 Intoxication, 317, 361 Intracellular, 34, 49, 54, 85, 86, 286, 315, 317, 323, 329, 338, 340, 344, 349 Intracellular Membranes, 317, 323 Intracranial Aneurysm, 289, 317, 318 Intracranial Arteriosclerosis, 289, 317 Intracranial Hypertension, 310, 318, 356 Intramuscular, 318, 333 Intravenous, 20, 179, 256, 257, 316, 318, 333 Intravenous pyelogram, 256, 257, 318 Intrinsic, 82, 173, 178, 275, 282, 318

Intubation, 287, 318 Invasive, 11, 51, 108, 111, 170, 171, 175, 194, 198, 224, 253, 260, 314, 318, 322 Involuntary, 194, 203, 255, 305, 318, 327, 344, 349, 350, 352, 355 Ion Channels, 37, 38, 281, 318, 329, 353 Ionization, 80, 318 Ionizing, 276, 302, 318, 343 Ions, 188, 282, 298, 300, 313, 318, 325 Irrigation, 26, 140, 178, 318 Irritable Bowel Syndrome, 36, 71, 91, 120, 193, 195, 196, 252, 254, 306, 318 Irritants, 28, 82, 182, 189, 318 Ischemia, 78, 90, 281, 297, 318 J Joint, 67, 187, 275, 281, 291, 318, 332, 353, 354 K Kallidin, 285, 318 Kb, 69, 236, 319 Keloid, 179, 319 Keratinocytes, 317, 319 Keratitis, 173, 319 Keratoconjunctivitis, 173, 319 Ketoconazole, 173, 319 Ketone Bodies, 273, 319 Kidney Disease, 5, 10, 17, 23, 30, 35, 165, 168, 176, 197, 206, 236, 242, 244, 258, 319 Kidney Pelvis, 319, 358 Kidney stone, 256, 319, 332, 345, 352 Kinetic, 82, 318, 319 L Labile, 292, 319 Labyrinth, 319, 360 Lactation, 319, 331, 332 Lactobacillus, 57, 76, 92, 94, 162, 319 Lactose Intolerance, 196, 319 Large Intestine, 196, 288, 292, 298, 317, 319, 344, 349 Laser Surgery, 253, 320 Latent, 39, 76, 320, 338 Lavage, 30, 147, 148, 320 Lectin, 320, 323 Leisure Activities, 26, 320 Lens, 320, 345 Lesion, 76, 175, 320, 321, 348, 358 Lethal, 282, 320, 326 Lethargy, 193, 320 Leucocyte, 276, 302, 320, 322 Leukaemia, 100, 320 Leukemia, 114, 299, 320

Index 373

Leukocytes, 59, 79, 84, 285, 290, 310, 317, 320, 357 Leukoencephalopathy, 76, 320 Leukotrienes, 280, 300, 320 Library Services, 266, 320 Lidocaine, 12, 97, 189, 320 Ligament, 320, 341 Ligands, 45, 60, 177, 320 Ligation, 320 Light microscope, 185, 320 Lipid, 280, 286, 288, 316, 321, 326 Lipomatosis, 125, 142, 321 Lipophilic, 72, 321 Lipopolysaccharide, 67, 93, 310, 321 Lipoprotein, 180, 310, 321 Liver scan, 321, 347 Localization, 46, 72, 82, 314, 321 Localized, 173, 188, 305, 310, 315, 321, 331, 336, 347, 358, 359 Locus Coeruleus, 37, 321 Long-Term Care, 16, 321 Low-density lipoprotein, 321 Luciferase, 54, 321 Lumbar, 119, 282, 321, 347, 355 Lumen, 178, 183, 302, 321 Lupus, 95, 119, 176, 321, 354 Lymph, 95, 289, 301, 302, 321, 322, 352 Lymph node, 289, 321, 322 Lymphadenopathy, 95, 321 Lymphatic, 302, 315, 321, 322, 324, 331, 350, 355 Lymphatic system, 321, 322, 350, 355 Lymphoblastic, 322 Lymphoblasts, 273, 322 Lymphocyte, 279, 322, 323 Lymphoid, 279, 310, 320, 322 Lymphoma, 112, 322 Lysine, 296, 313, 322 Lytic, 322, 348, 360 M Magnesium Hydroxide, 251, 322 Magnetic Resonance Imaging, 322, 347 Major Histocompatibility Complex, 317, 322 Malaise, 176, 322 Malformation, 322, 345 Malignancy, 72, 113, 198, 322 Malignant, 137, 195, 198, 274, 279, 287, 322, 326, 328, 332, 343, 346 Malignant tumor, 198, 287, 322, 326, 332, 346 Mammary, 195, 322

Mastitis, 195, 322 Mastocytosis, 83, 322 Matrilysin, 55, 322 Matrix metalloproteinase, 56, 322 Medial, 323, 331, 355 Mediate, 41, 72, 299, 323 Mediator, 60, 72, 84, 85, 317, 323, 337, 348 Medical Assistance, 255, 323 Medical Records, 14, 323 MEDLINE, 7, 20, 237, 323 Medullary, 216, 323 Meiosis, 323, 353 Melanin, 321, 323, 358 Melanocytes, 323 Melanoma, 49, 323 Membrane Proteins, 41, 288, 323 Memory, 279, 323 Meninges, 289, 295, 323 Meningitis, 323 Meningoencephalitis, 76, 323 Menopause, 28, 209, 323, 331, 338, 339 Menstrual Cycle, 75, 176, 193, 306, 323, 331, 339 Menstruation, 300, 306, 323, 339 Mental Disorders, 168, 324 Mental Health, iv, 15, 16, 35, 168, 236, 239, 324, 342 Menthol, 201, 202, 324 Mercury, 306, 324 Mesencephalic, 321, 324 Mesenchymal, 281, 303, 324 Mesna, 148, 152, 228, 230, 324 Metabolite, 46, 49, 298, 313, 324 Metastasis, 72, 323, 324, 328 Methionine, 162, 298, 324, 353 MI, 101, 192, 272, 324 Microbe, 324, 356 Microbiological, 6, 77, 324 Microbiology, 68, 69, 84, 91, 101, 105, 110, 274, 281, 282, 324 Microorganism, 292, 324, 333, 361 Microscopy, 51, 69, 72, 283, 324, 330 Microscopy, Polarization, 72, 324 Micturition, 49, 74, 82, 141, 188, 194, 202, 324 Migration, 45, 81, 90, 174, 324 Milliliter, 33, 179, 324 Mitochondria, 46, 325, 332 Mitochondrial Swelling, 325, 327 Mitomycin, 108, 325 Mitosis, 280, 325 Mitotic, 303, 325, 360

374 Cystitis

Mixed Connective Tissue Disease, 185, 325 Modeling, 39, 325 Modification, 12, 22, 23, 29, 66, 90, 212, 214, 218, 307, 325, 343 Modulator, 62, 325 Molecular mass, 56, 325 Molecular Structure, 325, 357 Monitor, 19, 211, 287, 295, 325, 330 Monoclonal, 43, 45, 84, 312, 325, 343 Monoclonal antibodies, 43, 45, 84, 325 Monocyte, 45, 326 Mononuclear, 20, 199, 326, 357 Monophosphate, 24, 326 Monotherapy, 189, 326 Morphine, 188, 326, 327, 331 Morphological, 38, 53, 72, 186, 301, 306, 323, 326 Morphology, 72, 81, 185, 326 Motility, 196, 306, 326, 348 Motion Sickness, 326, 327 Motor nerve, 326 Mucinous, 307, 326 Mucosa, 6, 25, 69, 174, 178, 200, 202, 302, 321, 326 Mucosal Lining, 42, 189, 326 Mucositis, 326, 355 Mucus, 304, 326, 358 Multicenter Studies, 62, 326 Multicenter study, 326 Multiple Myeloma, 216, 326 Multiple sclerosis, 177, 185, 203, 326 Muscle relaxant, 173, 224, 326 Muscle tension, 326 Muscular Dystrophies, 300, 326 Musculature, 44, 66, 78, 326 Mustard Gas, 318, 326 Mutagenesis, 51, 88, 91, 327 Mutagens, 327 Myasthenia, 185, 327 Mycobacteriosis, 107, 327 Mydriatic, 298, 327 Myelin, 326, 327 Myocardium, 179, 324, 327 Myopathy, 104, 327 N Naloxone, 327 Naltrexone, 184, 327 Narcosis, 327 Narcotic, 184, 326, 327 Narcotic Antagonists, 184, 327 Nausea, 5, 35, 176, 279, 315, 327, 339, 358

NCI, 1, 167, 235, 327 Necrosis, 45, 136, 280, 289, 315, 324, 327 Neodymium, 136, 327 Neonatal, 33, 52, 327 Neoplasia, 21, 328 Neoplasms, 137, 274, 279, 287, 297, 311, 328, 343 Neoplastic, 278, 312, 322, 328 Nephritis, 76, 208, 215, 328 Nephropathy, 4, 90, 216, 319, 328 Nephrotoxic, 46, 328 Nerve Endings, 328, 329 Nerve Fibers, 82, 83, 121, 328, 355 Nerve Growth Factor, 49, 79, 129, 184, 328 Nervous System, 37, 73, 75, 76, 91, 202, 273, 275, 282, 283, 286, 289, 307, 309, 310, 320, 323, 326, 327, 328, 329, 331, 335, 342, 348, 353, 354 Nervousness, 176, 328 Networks, 80, 328 Neural, 37, 80, 85, 177, 187, 202, 275, 277, 286, 328 Neuroendocrine, 86, 92, 328 Neurogenic, 4, 51, 59, 71, 85, 141, 177, 202, 328, 358 Neurologic, 203, 328 Neuromuscular, 273, 328, 354 Neuronal, 38, 52, 70, 74, 81, 327, 328 Neurons, 37, 38, 49, 54, 72, 74, 85, 188, 297, 307, 326, 328, 329, 353, 360 Neuropathy, 187, 328, 335 Neuropeptide, 74, 286, 328 Neurotensin, 83, 329 Neurotoxic, 49, 329 Neurotoxicity, 49, 329 Neurotransmitters, 277, 299, 326, 328, 329, 339 Neutrons, 276, 329, 343 Neutropenia, 36, 329, 337 Neutrophil, 35, 45, 72, 174, 329 Nitrates, 24, 329 Nitric acid, 329 Nitric Oxide, 55, 70, 72, 79, 85, 87, 106, 141, 196, 197, 329 Nitrofurantoin, 17, 27, 33, 171, 215, 229, 329 Nitrogen, 276, 277, 296, 304, 305, 309, 325, 329, 357 Nociceptors, 37, 329 Nocturia, 9, 10, 14, 18, 19, 25, 73, 186, 202, 329 Nonmalignant, 9, 13, 329

Index 375

Norepinephrine, 36, 275, 277, 299, 329 Norfloxacin, 27, 94, 330 Nosocomial, 55, 88, 91, 330 Nuclear, 79, 83, 86, 118, 119, 126, 199, 257, 282, 300, 303, 307, 325, 327, 330 Nuclear Matrix, 79, 330 Nuclear Pore, 330 Nucleic acid, 195, 197, 307, 312, 315, 327, 329, 330 Nucleic Acid Hybridization, 312, 330 Nucleolus, 330, 346 Nucleus, 79, 86, 280, 282, 290, 296, 303, 307, 321, 323, 326, 329, 330, 340, 341, 352, 360 Nurse Practitioners, 116, 217, 330 Nursing Care, 330, 334 Nursing Staff, 12, 330 O Observational study, 40, 330 Obstetrics, 44, 51, 95, 104, 112, 123, 125, 134, 190, 330 Odds Ratio, 26, 330, 345 Oedema, 177, 331 Oestrogen, 99, 105, 123, 331 Ofloxacin, 27, 94, 331 Ointments, 173, 331, 361 Oncogenic, 331, 338 Oncogenic Viruses, 331, 338 Opacity, 297, 331 Opium, 326, 331 Optic Chiasm, 313, 331 Optic Nerve, 284, 331, 345 Orbital, 292, 331 Organ Culture, 331, 356 Organelles, 41, 69, 296, 323, 332, 337 Ornithine, 296, 332 Osteoarthritis, 332, 336 Osteogenic sarcoma, 332 Osteoporosis, 331, 332 Osteosarcoma, 48, 332 Otitis, 152, 332 Outpatient, 6, 20, 21, 35, 43, 70, 332 Ovalbumin, 41, 58, 78, 332 Ovaries, 304, 332, 345, 348, 354, 357 Ovary, 48, 295, 303, 309, 331, 332, 337 Overactive bladder, 192, 202, 332 Ovulation, 95, 306, 332 Ovulation Induction, 95, 332 Ovum, 295, 332, 339 Oxalate, 332, 358 Oxygen Consumption, 46, 332, 345 Oxygenation, 90, 332

Oxytetracycline, 147, 332 Oxytocin, 73, 92, 332 P Pain Measurement, 50, 332 Painful bladder syndrome, 37, 79, 206, 332 Palliative, 15, 66, 331, 333, 355 Pancreas, 273, 284, 298, 316, 333, 357 Papain, 193, 333 Papovaviridae, 333, 338 Paralysis, 295, 324, 333, 350, 354 Parasitic, 283, 333 Parenteral, 55, 105, 184, 333 Paresthesia, 333, 354 Parietal, 177, 333, 335, 337 Parietal Cells, 177, 333 Parietal Lobe, 333 Partial remission, 170, 201, 333, 345 Partial response, 333 Particle, 333, 350, 356 Partnership Practice, 333, 339 Parturition, 330, 333 Patella, 216, 333 Pathogen, 34, 40, 69, 97, 190, 333 Pathologic, 14, 30, 72, 87, 206, 280, 284, 294, 313, 333, 342 Pathologic Processes, 280, 333 Pathophysiology, 5, 9, 11, 20, 21, 27, 47, 56, 60, 62, 79, 84, 85, 124, 125, 333 Patient Advocacy, 56, 245, 259, 333 Patient Care Management, 22, 213, 334 Patient Education, 19, 32, 34, 218, 219, 245, 255, 264, 266, 272, 334 Pefloxacin, 94, 334 Pelvic inflammatory disease, 245, 334 Penicillin, 277, 279, 287, 334 Penis, 32, 248, 270, 334, 345 Pentosan polysulfate, 11, 21, 57, 60, 96, 119, 127, 173, 203, 206, 224, 334 Pentosyltransferases, 309, 334 Pepsin, 291, 334 Pepsin A, 291, 334 Peptide, 45, 49, 51, 88, 187, 199, 200, 286, 334, 338, 341 Peptide T, 88, 200, 334 Perception, 34, 71, 196, 334, 347 Percutaneous, 9, 111, 125, 129, 152, 334 Perfusion, 284, 314, 334 Pericardium, 334, 354 Perineal, 13, 39, 111, 186, 206, 334 Perineum, 32, 334 Peripheral blood, 101, 311, 317, 334

376 Cystitis

Peripheral Nervous System, 187, 335, 339, 353 Peripheral Neuropathy, 203, 335 Peritoneal, 281, 331, 335 Peritoneal Cavity, 281, 331, 335 Peritoneum, 335, 346 Peritonitis, 95, 335 Perivascular, 177, 286, 335 Petechiae, 310, 335 Phagocytosis, 72, 76, 335 Pharmacodynamic, 94, 335 Pharmacologic, 37, 38, 85, 143, 278, 310, 335, 356, 358 Pharmacotherapy, 12, 30, 189, 335 Phenotype, 30, 52, 283, 335 Phenylacetate, 202, 335 Phosphodiesterase, 194, 335 Phosphodiesterase Inhibitors, 194, 335 Phospholipids, 304, 321, 335 Phosphorus, 286, 335, 336 Phosphorylation, 60, 336 Phosphotyrosine, 174, 336 Physical Examination, 14, 206, 214, 257, 290, 336 Physical Therapy, 12, 32, 336 Physician Assistants, 14, 336 Physiologic, 20, 71, 81, 106, 275, 284, 310, 323, 336, 340, 344 Physiology, 19, 67, 71, 90, 206, 283, 301, 310, 336 Pigment, 323, 336 Pilot study, 62, 67, 126, 336 Piroxicam, 106, 336 Placenta, 303, 306, 336, 339, 342 Plants, 276, 283, 291, 301, 308, 320, 326, 330, 336, 337, 346, 351, 356, 357 Plasma cells, 199, 279, 310, 326, 336 Plasma protein, 80, 275, 302, 336 Plasticity, 49, 74, 336 Plastids, 332, 337 Platelet Activating Factor, 79, 337 Platelet Aggregation, 278, 329, 337, 355 Platelet Count, 35, 337 Platelet Factor 4, 317, 337 Platelet Transfusion, 35, 337 Platelets, 283, 329, 337, 355 Platinum, 291, 337 Pleural, 331, 337 Pleural cavity, 331, 337 Podophyllotoxin, 303, 337 Point Mutation, 68, 124, 337 Poisoning, 317, 324, 327, 337

Pollen, 289, 337, 343 Polycystic, 197, 216, 338 Polycystic Kidney Diseases, 216, 338 Polymerase, 101, 338 Polymerase Chain Reaction, 101, 338 Polyomavirus, 101, 113, 114, 136, 333, 338 Polyp, 111, 338 Polypeptide, 49, 74, 277, 292, 303, 305, 312, 334, 338, 341, 361 Polyposis, 292, 338 Polysaccharide, 61, 122, 279, 309, 338, 341 Port, 180, 338 Port-a-cath, 338 Posterior, 154, 277, 282, 299, 332, 333, 338, 346 Postmenopausal, 13, 17, 28, 57, 120, 332, 338 Postnatal, 338, 351 Postoperative, 336, 338 Postsynaptic, 338, 349, 353 Potassium Chloride, 32, 246, 338 Potassium Citrate, 218, 338 Potentiate, 181, 339 Potentiating, 152, 277, 339 Practicability, 339, 357 Practice Guidelines, 17, 239, 257, 339 Precursor, 280, 296, 299, 300, 302, 329, 339, 357, 358 Prednisolone, 119, 339 Premenopausal, 57, 339 Premenstrual, 22, 175, 192, 193, 339 Premenstrual Syndrome, 175, 339 Presumptive, 12, 22, 339 Presynaptic, 299, 328, 339, 353 Presynaptic Terminals, 299, 328, 339 Prevalence, 4, 6, 8, 10, 14, 26, 31, 53, 57, 63, 115, 123, 127, 134, 143, 199, 331, 339 Primary tumor, 183, 339 Private Practice, 61, 339 Procaine, 320, 339 Progesterone, 193, 339, 351 Prognostic factor, 36, 340 Progression, 51, 62, 90, 184, 185, 198, 206, 278, 322, 340 Progressive, 48, 76, 185, 288, 290, 310, 326, 327, 332, 338, 340, 345, 346, 357 Projection, 297, 330, 331, 340 Proline, 292, 313, 340 Promoter, 41, 74, 88, 340 Prone, 6, 73, 200, 255, 340 Prophase, 340, 353

Index 377

Prophylaxis, 21, 28, 29, 93, 166, 185, 329, 340 Proportional, 178, 333, 340 Prospective study, 96, 128, 130, 136, 340 Prostaglandin, 72, 140, 142, 340, 355 Prostaglandins A, 340 Prostate gland, 203, 290, 341 Prostatic Hyperplasia, 156, 203, 341 Prostatitis, 9, 13, 23, 30, 46, 48, 53, 62, 63, 65, 84, 93, 105, 157, 188, 210, 215, 216, 256, 341 Protease, 77, 78, 193, 292, 341 Protective Agents, 286, 341 Protein C, 41, 79, 276, 277, 280, 282, 321, 341, 358 Protein Conformation, 277, 341 Protein Kinases, 54, 341 Protein S, 77, 209, 284, 307, 341, 346, 354 Proteinuria, 326, 341 Proteoglycans, 90, 140, 174, 283, 304, 341 Proteolytic, 188, 193, 276, 292, 305, 333, 341 Proteus, 4, 40, 77, 94, 147, 180, 181, 209, 210, 341 Protocol, 23, 44, 50, 62, 64, 65, 66, 218, 219, 251, 341 Protons, 276, 313, 318, 341, 343 Protozoa, 284, 324, 341 Proximal, 46, 82, 180, 298, 339, 342 Pruritic, 199, 300, 342 Pruritus, 313, 342 Pseudorabies, 83, 342 Psoriasis, 173, 179, 326, 342 Psychiatric, 283, 324, 342, 349 Psychic, 342 Psychogenic, 342, 358 Psychosomatic, 152, 249, 342 Public Assistance, 323, 342 Public Health, 54, 76, 219, 239, 342 Public Policy, 237, 342 Publishing, 19, 27, 31, 92, 211, 216, 342 Puerperium, 330, 342 Pulmonary, 179, 284, 302, 320, 342 Pulmonary Artery, 284, 342 Pulse, 325, 342 Pupil, 294, 298, 327, 342 Purpura, 216, 310, 342 Purulent, 273, 342, 359 Pyelitis, 113, 122, 190, 210, 342 Q Quality of Life, 9, 14, 15, 16, 18, 39, 47, 50, 53, 62, 65, 91, 102, 104, 185, 203, 343

Quercetin, 143, 155, 193, 251, 343 R Race, 64, 190, 324, 343 Radiation therapy, 255, 272, 274, 304, 313, 317, 334, 343 Radical cystectomy, 198, 343 Radioactive, 285, 310, 313, 315, 317, 318, 321, 325, 330, 331, 343, 347 Radioimmunotherapy, 343 Radiolabeled, 343 Radiological, 334, 343 Radiopharmaceutical, 307, 343 Radiotherapy, 100, 123, 285, 343 Random Allocation, 343 Randomization, 50, 343 Randomized, 42, 46, 47, 48, 50, 61, 62, 63, 64, 65, 66, 67, 94, 128, 140, 165, 167, 300, 344 Randomized clinical trial, 46, 344 Rarefaction, 281, 344 Reactivation, 76, 101, 344 Reagent, 197, 312, 321, 344 Receptors, Serotonin, 344, 348 Recombinant, 41, 74, 129, 201, 284, 344, 360 Reconstitution, 83, 344 Rectal, 166, 344 Rectum, 137, 210, 250, 280, 285, 292, 298, 305, 307, 315, 316, 319, 341, 344 Recurrence, 182, 198, 200, 251, 344 Red blood cells, 35, 303, 311, 344, 347 Reductase, 194, 203, 305, 344 Refer, 1, 285, 292, 299, 305, 306, 321, 329, 330, 343, 344, 360 Reflex, 27, 38, 49, 52, 150, 202, 344 Reflux, 4, 197, 243, 344 Refraction, 344, 351 Refractory, 9, 19, 110, 111, 114, 123, 124, 130, 149, 151, 238, 300, 344 Regeneration, 81, 344 Regimen, 6, 7, 20, 29, 291, 300, 335, 344 Regression Analysis, 298, 344 Relapse, 207, 345 Relative risk, 26, 345 Relaxant, 345 Remission, 7, 11, 14, 207, 218, 344, 345 Renal agenesis, 216, 345 Renal failure, 90, 99, 345 Renal pelvis, 82, 319, 345, 357 Renal tubular, 296, 345 Reproductive system, 341, 345 Research Design, 48, 345

378 Cystitis

Resection, 11, 148, 198, 345 Resolving, 51, 87, 251, 345 Respiration, 295, 325, 345 Response rate, 10, 42, 59, 345 Restoration, 336, 344, 345, 361 Retina, 284, 320, 331, 345, 346 Retroperitoneal, 115, 346 Retroperitoneal Fibrosis, 115, 346 Retroperitoneal Space, 346 Retrospective, 23, 25, 346 Retrovirus, 74, 346 Rhabdomyosarcoma, 98, 346 Rheumatism, 346 Rheumatoid, 4, 85, 185, 197, 336, 346 Rheumatoid arthritis, 4, 85, 185, 197, 336, 346 Ribonuclease, 325, 346 Ribonucleoproteins, 330, 346 Ribose, 274, 346, 355 Ribosome, 346, 357 Risk factor, 4, 6, 20, 22, 26, 28, 36, 38, 53, 56, 57, 101, 112, 119, 130, 214, 218, 252, 253, 255, 302, 340, 345, 346 Rod, 161, 282, 319, 341, 346 Rutin, 343, 346 S Saccule, 346, 360 Saline, 325, 346 Saliva, 346 Salivary, 179, 296, 298, 346, 352 Salivary glands, 296, 298, 346 Saponins, 286, 346, 351 Scans, 119, 257, 347 Schizoid, 347, 361 Schizophrenia, 347, 361 Schizotypal Personality Disorder, 347, 361 Sciatic Nerve, 347, 355 Scleroderma, 177, 325, 347 Sclerosis, 177, 188, 317, 326, 347 Screening, 25, 33, 40, 50, 183, 189, 195, 199, 291, 347, 358 Scrotum, 32, 347, 354 Sebaceous, 318, 347, 361 Sebaceous gland, 318, 347, 361 Secondary tumor, 324, 347 Secretion, 84, 177, 291, 295, 303, 312, 316, 317, 319, 326, 347, 348, 359 Secretory, 179, 347, 353 Sedative, 277, 313, 347 Sediment, 347, 358 Segregation, 282, 347 Self Care, 205, 212, 217, 273, 347

Self-Help Groups, 134, 154, 348 Semen, 340, 341, 348 Semisynthetic, 277, 289, 303, 348 Sensibility, 277, 313, 348 Sensitization, 37, 52, 71, 81, 348 Sensor, 198, 348 Sepsis, 91, 197, 348 Septic, 281, 341, 348 Sequence Homology, 334, 348 Sequencing, 56, 69, 338, 348 Serologic, 314, 348 Serotonin, 188, 193, 277, 335, 344, 348, 357 Serous, 302, 348 Sex Characteristics, 274, 331, 348, 354 Sexually Transmitted Diseases, 3, 245, 251, 348 Shedding, 76, 84, 348 Shock, 176, 192, 278, 348, 357 Sialyltransferases, 309, 349 Signal Transduction, 288, 336, 349 Signs and Symptoms, 12, 197, 252, 253, 345, 349 Sitz Bath, 15, 173, 349 Skeletal, 70, 295, 326, 349, 350 Skeleton, 35, 273, 318, 340, 349 Skull, 295, 349, 354 Sleep Deprivation, 7, 349 Small intestine, 288, 290, 299, 302, 312, 314, 317, 349 Smooth muscle, 70, 81, 140, 188, 194, 196, 278, 286, 294, 312, 313, 326, 349, 350, 353 Sneezing, 348, 349, 352 Social Environment, 343, 349 Social Isolation, 198, 347, 349 Social Support, 15, 349 Social Work, 254, 350 Sodium, 30, 52, 127, 131, 145, 172, 173, 178, 189, 206, 219, 224, 230, 350 Sodium Bicarbonate, 145, 189, 350 Soft tissue, 285, 349, 350 Solid tumor, 278, 284, 299, 350 Solvent, 273, 283, 350, 358 Soma, 350 Somatic, 38, 52, 74, 75, 274, 323, 325, 335, 350 Somatomedins, 316, 350 Sonogram, 248, 350 Sound wave, 293, 350 Spasm, 194, 280, 324, 350 Spasmodic, 273, 350 Spastic, 183, 318, 350 Spasticity, 350

Index 379

Spatial disorientation, 299, 350 Specialist, 260, 298, 350 Specificity, 7, 51, 131, 275, 351 Spectrum, 6, 10, 20, 40, 51, 63, 65, 74, 77, 198, 319, 330, 334, 351 Sperm, 222, 290, 337, 351, 354 Sphincter, 38, 188, 351, 352 Spices, 250, 351 Spina bifida, 4, 351 Spinal cord, 49, 203, 281, 289, 290, 301, 307, 323, 328, 335, 344, 347, 351, 353 Spinal Nerves, 335, 351 Spinous, 303, 319, 351 Sporadic, 55, 172, 351 Staging, 72, 347, 351 Stasis, 182, 351 Statistically significant, 25, 351 Stem cell transplantation, 82, 101, 311, 351 Stem Cells, 35, 70, 82, 276, 311, 351 Sterile, 75, 178, 281, 351 Sterility, 6, 296, 316, 351 Steroid, 173, 189, 295, 331, 346, 351 Stimulant, 188, 228, 286, 312, 319, 352 Stimulus, 52, 71, 294, 299, 300, 304, 316, 317, 318, 344, 352, 355 Stomach, 4, 176, 177, 273, 298, 303, 307, 312, 320, 327, 333, 334, 335, 344, 349, 352 Stool, 315, 318, 320, 352 Strand, 338, 352 Streptococcal, 179, 352 Streptococcus, 91, 178, 352 Stress incontinence, 198, 199, 352 Stress urinary, 26, 70, 352 Stricture, 82, 188, 210, 352 Stroke, 168, 203, 236, 352 Stroma, 111, 352 Stromal, 301, 352 Struvite, 181, 352, 358 Stupor, 320, 327, 352 Subacute, 83, 315, 352 Subarachnoid, 306, 310, 352 Subclinical, 203, 315, 352 Subcutaneous, 179, 300, 331, 333, 352 Submaxillary, 303, 352 Subspecies, 350, 352 Substance P, 187, 324, 344, 347, 352 Succinimides, 46, 353 Sulfur, 287, 304, 324, 353 Superoxide, 194, 353 Support group, 21, 23, 353 Suppression, 208, 295, 329, 353 Suppressive, 30, 353

Sympathetic Nervous System, 282, 353 Sympathomimetic, 192, 299, 303, 330, 353 Symphysis, 341, 353 Symptomatic, 11, 16, 18, 22, 68, 76, 88, 108, 127, 130, 166, 189, 194, 203, 353 Symptomatic treatment, 127, 130, 353 Symptomatology, 16, 24, 33, 78, 96, 132, 353 Synapsis, 353 Synaptic, 49, 349, 353 Synaptic Transmission, 49, 353 Synergistic, 353, 355 Synovial, 281, 354 Synovial Membrane, 281, 354 Systemic disease, 281, 354 Systemic lupus erythematosus, 105, 110, 123, 185, 325, 354 Systemic therapy, 183, 354 Systolic, 310, 313, 354 T Tachykinins, 187, 354 Tear Gases, 318, 354 Temozolomide, 113, 354 Temporal, 55, 75, 311, 354 Tennis Elbow, 187, 354 Teratogenic, 276, 298, 354 Testicles, 347, 354 Testicular, 149, 354 Testis, 303, 331, 354 Testosterone, 73, 194, 203, 273, 305, 344, 354 Tetracycline, 74, 299, 354 Tetrodotoxin, 37, 38, 354 Therapeutics, 41, 59, 83, 230, 355 Thermal, 75, 188, 298, 329, 338, 355 Thigh, 343, 355 Third Ventricle, 314, 355 Thoracic, 282, 298, 355 Thorax, 273, 321, 355 Threonine, 334, 355 Threshold, 52, 171, 304, 313, 355 Thrombin, 305, 337, 341, 355 Thrombocytopenia, 337, 355 Thrombolytic, 180, 355 Thrombomodulin, 341, 355 Thrombosis, 179, 283, 318, 341, 352, 355 Thromboxanes, 280, 300, 355 Thrombus, 294, 315, 337, 355 Thymidine, 124, 355 Thymidine Phosphorylase, 124, 355 Thymus, 314, 322, 355 Tibial Nerve, 154, 347, 355

380 Cystitis

Tic, 118, 355 Tin, 5, 333, 335, 337, 355 Tinnitus, 5, 332, 356, 360 Tissue Culture, 178, 356 Tissue Extracts, 56, 356 Tomography, 72, 293, 356 Tooth Preparation, 274, 356 Topical, 173, 180, 201, 202, 281, 333, 350, 356, 361 Toxic, iv, 46, 59, 276, 282, 283, 295, 297, 301, 302, 314, 328, 329, 337, 356 Toxicity, 35, 45, 113, 140, 149, 299, 301, 324, 356, 358 Toxicology, 59, 114, 141, 238, 356 Toxins, 84, 279, 301, 308, 315, 323, 325, 343, 356 Trace element, 355, 356 Transcriptase, 346, 356 Transcutaneous, 22, 32, 148, 155, 219, 224, 356 Transduction, 54, 90, 349, 356 Transfection, 284, 356 Transfer Factor, 314, 356 Transfusion, 35, 356 Transitional cell carcinoma, 198, 357 Translating, 47, 357 Translation, 52, 91, 357 Translational, 61, 72, 86, 357 Transmitter, 273, 281, 299, 318, 323, 330, 357 Transplantation, 97, 99, 101, 109, 112, 113, 114, 118, 127, 130, 132, 133, 136, 142, 150, 153, 197, 285, 290, 314, 322, 357 Transurethral, 148, 198, 357 Trauma, 89, 179, 183, 327, 357 Treatment Outcome, 65, 357 Triage, 15, 29, 357 Tricyclic, 21, 173, 219, 277, 299, 357 Trimethoprim-sulfamethoxazole, 6, 16, 100, 357 Trophic, 70, 357 Tropism, 43, 51, 357 Tryptophan, 292, 348, 357 Tubal ligation, 128, 357 Tuberculosis, 111, 215, 321, 327, 357 Tumor marker, 284, 357 Tumor Necrosis Factor, 44, 85, 357 Tumour, 307, 357 Turpentine, 149, 358 Tyrosine, 299, 336, 358

U Ulcer, 25, 103, 116, 155, 186, 212, 297, 310, 358 Ulceration, 170, 210, 297, 358 Ulcerative colitis, 45, 111, 141, 316, 358 Unconscious, 278, 297, 314, 358 Urea, 52, 77, 181, 183, 332, 358 Uremia, 345, 358 Ureter, 82, 89, 256, 319, 345, 357, 358 Ureteritis, 113, 122, 210, 358 Urethritis, 21, 190, 206, 210, 213, 250, 256, 358 Urethrotomy, 210, 358 Urinalysis, 4, 14, 242, 251, 255, 256, 257, 271, 358 Urinary Calculi, 210, 358 Urinary Retention, 141, 188, 252, 358 Urinary urgency, 13, 19, 25, 39, 61, 75, 89, 174, 185, 195, 224, 253, 254, 358 Urinate, 10, 14, 32, 176, 202, 212, 217, 224, 248, 250, 254, 255, 256, 270, 271, 358, 361 Urine, 6, 12, 16, 19, 20, 21, 24, 28, 29, 30, 31, 32, 33, 36, 37, 51, 52, 56, 59, 67, 69, 72, 75, 79, 80, 82, 83, 87, 88, 89, 95, 96, 97, 98, 102, 103, 131, 135, 136, 144, 170, 171, 175, 179, 180, 181, 182, 184, 188, 190, 191, 197, 198, 199, 201, 202, 203, 209, 210, 211, 212, 213, 218, 219, 222, 242, 243, 245, 248, 250, 251, 254, 255, 256, 257, 269, 270, 271, 282, 283, 284, 295, 299, 303, 309, 311, 315, 318, 319, 324, 330, 332, 341, 342, 345, 352, 358, 359, 360 Urine Testing, 245, 359 Urodynamic, 7, 19, 39, 44, 63, 66, 136, 184, 203, 219, 359 Urogenital, 172, 194, 197, 218, 308, 309, 359 Urogenital Diseases, 359 Urolithiasis, 4, 215, 359 Urologic Diseases, 216, 242, 243, 244, 359 Urologist, 15, 19, 31, 224, 253, 254, 359 Urothelium, 25, 37, 38, 41, 56, 61, 78, 82, 85, 86, 89, 174, 359 Urticaria, 177, 278, 289, 313, 359 Uterine Contraction, 332, 359 Uterus, 289, 295, 301, 304, 306, 314, 324, 329, 332, 339, 345, 357, 359 V Vaccine, 41, 69, 172, 190, 200, 244, 274, 276, 341, 359 Vacuoles, 301, 332, 359

Index 381

Vagina, 21, 22, 173, 180, 194, 224, 250, 289, 297, 319, 323, 345, 359, 361 Vaginal, 6, 28, 57, 76, 166, 173, 212, 242, 250, 359, 361 Vaginitis, 11, 21, 172, 173, 359 Valganciclovir, 103, 359 Valves, 197, 359 Vascular, 25, 59, 83, 90, 177, 278, 286, 302, 310, 311, 313, 315, 317, 329, 331, 336, 355, 359 Vascular endothelial growth factor, 90, 359 Vasoactive, 83, 90, 359 Vasodilatation, 184, 319, 359 Vasodilator, 285, 286, 299, 312, 359 Vector, 356, 360 Vein, 281, 318, 330, 360 Venous, 180, 281, 283, 289, 311, 331, 337, 341, 360 Venous blood, 289, 337, 360 Venules, 285, 286, 302, 360 Verapamil, 184, 360 Vertebrae, 351, 360 Vertebral, 188, 283, 351, 360 Vertigo, 332, 360 Vesicoureteral, 4, 243, 360 Vesicular, 54, 360 Vestibular, 173, 360 Vestibule, 173, 346, 360 Vestibulocochlear Nerve, 356, 360 Vestibulocochlear Nerve Diseases, 356, 360 Veterinary Medicine, 237, 360 Vinblastine, 149, 360

Vinca Alkaloids, 360 Viral, 4, 76, 301, 331, 346, 356, 360 Virulence, 4, 41, 55, 69, 77, 88, 91, 93, 105, 136, 178, 211, 281, 356, 360 Virulent, 6, 54, 360 Virus, 76, 83, 85, 98, 99, 101, 124, 136, 282, 289, 307, 309, 317, 338, 356, 360, 361 Viscera, 91, 350, 361 Visceral, 9, 38, 74, 75, 81, 91, 282, 335, 361 Visual field, 284, 331, 361 Vitro, 58, 82, 88, 178, 311, 361 Vivo, 58, 72, 82, 93, 361 Void, 25, 188, 203, 254, 361 Voiding cystourethrogram, 257, 361 Volition, 318, 361 Vulgaris, 158, 159, 361 Vulva, 21, 173, 361 W Weight Gain, 176, 193, 361 White blood cell, 202, 273, 279, 283, 320, 322, 326, 329, 336, 361 Withdrawal, 193, 361 Wound Healing, 79, 83, 179, 201, 290, 323, 361 X Xenograft, 48, 278, 361 X-ray, 248, 293, 306, 307, 318, 330, 343, 347, 361 Y Yeasts, 306, 335, 361 Z Zinc Oxide, 173, 361 Zymogen, 341, 361

382 Cystitis

Index 383

384 Cystitis

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

Interstitial Cystitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Facial Paralysis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Breast Augmentation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Erythema Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Alopecia Areata - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Interstitial Cystitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Facial Paralysis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Breast Augmentation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Erythema Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Alopecia Areata - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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