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

INTERSTITIAL CYSTITIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES ...

Author: Health Publica Icon Health Publications

45 downloads 626 Views 2MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!

Report copyright / DMCA form

DOWNLOAD PDF

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

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

ii

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Interstitial Cystitis: 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: 0-597-83944-1 1. Interstitial Cystitis-Popular works. I. Title.

iii

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.

iv

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 interstitial 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.

v

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.

vi

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

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON INTERSTITIAL CYSTITIS ............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Interstitial Cystitis...................................................................... 26 The National Library of Medicine: PubMed ................................................................................ 73 CHAPTER 2. NUTRITION AND INTERSTITIAL CYSTITIS ................................................................. 117 Overview.................................................................................................................................... 117 Finding Nutrition Studies on Interstitial Cystitis .................................................................... 117 Federal Resources on Nutrition ................................................................................................. 121 Additional Web Resources ......................................................................................................... 121 CHAPTER 3. ALTERNATIVE MEDICINE AND INTERSTITIAL CYSTITIS ........................................... 123 Overview.................................................................................................................................... 123 National Center for Complementary and Alternative Medicine................................................ 123 Additional Web Resources ......................................................................................................... 128 General References ..................................................................................................................... 129 CHAPTER 4. DISSERTATIONS ON INTERSTITIAL CYSTITIS ............................................................. 131 Overview.................................................................................................................................... 131 Dissertations on Interstitial Cystitis ......................................................................................... 131 Keeping Current ........................................................................................................................ 131 CHAPTER 5. CLINICAL TRIALS AND INTERSTITIAL CYSTITIS ........................................................ 133 Overview.................................................................................................................................... 133 Recent Trials on Interstitial Cystitis ......................................................................................... 133 Keeping Current on Clinical Trials ........................................................................................... 134 CHAPTER 6. PATENTS ON INTERSTITIAL CYSTITIS ........................................................................ 137 Overview.................................................................................................................................... 137 Patents on Interstitial Cystitis................................................................................................... 137 Patent Applications on Interstitial Cystitis............................................................................... 152 Keeping Current ........................................................................................................................ 162 CHAPTER 7. BOOKS ON INTERSTITIAL CYSTITIS............................................................................ 163 Overview.................................................................................................................................... 163 Book Summaries: Federal Agencies............................................................................................ 163 Book Summaries: Online Booksellers......................................................................................... 165 Chapters on Interstitial Cystitis ................................................................................................ 166 Directories.................................................................................................................................. 169 CHAPTER 8. MULTIMEDIA ON INTERSTITIAL CYSTITIS ................................................................. 171 Overview.................................................................................................................................... 171 Video Recordings ....................................................................................................................... 171 Bibliography: Multimedia on Interstitial Cystitis ..................................................................... 172 CHAPTER 9. PERIODICALS AND NEWS ON INTERSTITIAL CYSTITIS .............................................. 173 Overview.................................................................................................................................... 173 News Services and Press Releases.............................................................................................. 173 Newsletter Articles .................................................................................................................... 175 Academic Periodicals covering Interstitial Cystitis ................................................................... 176 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 177 Overview.................................................................................................................................... 177 U.S. Pharmacopeia..................................................................................................................... 177 Commercial Databases ............................................................................................................... 178 Researching Orphan Drugs ....................................................................................................... 179 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 183 Overview.................................................................................................................................... 183

viii Contents

NIH Guidelines.......................................................................................................................... 183 NIH Databases........................................................................................................................... 185 Other Commercial Databases..................................................................................................... 188 APPENDIX B. PATIENT RESOURCES ............................................................................................... 189 Overview.................................................................................................................................... 189 Patient Guideline Sources.......................................................................................................... 189 Associations and Interstitial Cystitis......................................................................................... 202 Finding Associations.................................................................................................................. 203 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 205 Overview.................................................................................................................................... 205 Preparation................................................................................................................................. 205 Finding a Local Medical Library................................................................................................ 205 Medical Libraries in the U.S. and Canada ................................................................................. 205 ONLINE GLOSSARIES................................................................................................................ 211 Online Dictionary Directories ................................................................................................... 213 INTERSTITIAL CYSTITIS DICTIONARY............................................................................... 215 INDEX .............................................................................................................................................. 289

1

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 interstitial cystitis is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about interstitial 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 interstitial 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 interstitial 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 interstitial 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 interstitial cystitis. The Editors

1

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

3

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

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

4

Interstitial Cystitis

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. •

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) 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

Studies

5

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. •

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.

•

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).

•

Self-Care Regimens for Patients With Interstitial Cystitis Source: Urologic Clinics of North America. 21(1): 121-130. February 1994.

6

Interstitial Cystitis

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. •

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).

•

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.

•

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

Studies

7

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). •

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.

•

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 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

8

Interstitial Cystitis

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.

•

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 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.

Studies

•

9

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.

•

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.

•

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 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.

10

Interstitial Cystitis

•

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).

•

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.

•

Interstitial Cystitis: Update on Etiologies and Therapeutic Options Source: Journal of Women's Health and Gender-Based Medicine. 8(6): 745-758. 1999.

Studies

11

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. •

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.

•

Epidemiology of Interstitial Cystitis: A Population Based Study Source: Journal of Urology. 161(2): 549-552. February 1999.

12

Interstitial Cystitis

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). •

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).

•

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 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

Studies

13

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.

•

Understanding Chronic Pelvic Pain Syndrome Source: Current Opinion in Urology. 12(1): 63-67. January 2002. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London, SE1 1GB, UK. +44 (0) 171940-7500. E-mail: [email protected]. Summary: Patients with noninflammatory chronic pelvic pain syndrome, the largest group of prostatitis patients according to the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) of the National Institutes of Health classification, are characterized by the absence of objective findings. Nothing thus links the symptoms of this disease to the prostate or other male organs in particular. For this reason, observations on interstitial cystitis (IC) in women are of interest to understand the chronic pelvic pain syndrome (CPPS). This article updates readers on the current understanding of CPPS, by commenting on recent publications in the light of older knowledge and the classification of prostatitis. New information from studies on the inflammatory response in expressed prostatic secretion in patients with CPPS and in bladder tissue from patients with IC indicates that complex systems on the cytokine gene expression level may be operating in these diseases. Research findings point to a common denominator at the level of molecular biology that might explain how the symptoms of CPPS and IC can be precipitated by pathogens, inflammatory reactions, and even neurological mechanisms. The initial clinical trial reports of drugs that

14

Interstitial Cystitis

modulate the inflammatory response in IC are met with great interest. 27 references (10 annotated). •

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 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.

Studies

•

15

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).

•

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

16

Interstitial Cystitis

•

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.

•

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

Studies

17

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). •

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).

•

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

•

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.

18

Interstitial Cystitis

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. •

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.

•

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).

•

Interstitial Cystitis: Diagnosis and Treatment Source: Innovations in Urology Nursing. 5(3): 38-43. 1994.

Studies

19

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. •

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.

•

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 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).

20

Interstitial Cystitis

•

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.

•

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 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.

•

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.

Studies

•

21

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 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.

•

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.

22

Interstitial Cystitis

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 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).

•

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

Studies

23

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). •

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.

•

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

•

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

24

Interstitial Cystitis

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). •

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

•

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

Studies

25

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 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.

•

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

26

Interstitial Cystitis

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

Project Title: ADRENOCEPTOR FUNCTION IN CATS WITH INTERSTITIAL CYSTITIS Principal Investigator & Institution: Westropp, Jodi L.; Veterinary Clinical Sciences; Ohio State University 1960 Kenny Road 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

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

Studies

27

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 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

•

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

28

Interstitial Cystitis

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 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.

Studies

29

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 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

30

Interstitial Cystitis

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 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

•

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

Studies

31

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 immune polarization in the development of this disease. This transgenic mouse strain (termed URO-OVA) will be genetically engineered with DNA containing a bladder-specific 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

32

Interstitial Cystitis

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 •

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 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

Studies

33

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 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: BLADDER INFLAMMATION

TRANSCRIPTOME

IN

EXPERIMENTAL

Principal Investigator & Institution: Saban, Ricardo; Associate Professor; Physiology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Interstitial Cystitis (IC) is a chronic bladder syndrome characterized by urinary urgency, frequency, nocturia pain and sterile urine. Although inflammation is not a universal characteristic of biopsies from IC patients, it seems that inflammation underline all major bladder pathologies including malignancy and represents a defense reaction to injury caused by physical damage, chemical substances, microorganisms or other gents. Indeed, areas of bladder inflammation are found in bladder disease including carcinoma, during chronic implantation of catheters, and an integrative part of bladder responses to intravesical Bacillus Calmette-Guerin (BCG). Although BCG has been proposed as a promising option for treatment of IC its mechanisms of action is not completely known. One of the theories is that intravesical BCG may be effective in treating by correcting an aberrant immune imbalance in the bladder, leading to long-term symptomatic improvement. It remains to be determined the nature of this immune imbalance. As nuclear factor kappaB (NFkappaB) has been described to modulate both bladder inflammation and the effects of BCG therapy, it is fair to propose, as a central hypothesis, that intravesical BCG leads to activation of NFkappaB and translation of pro- and anti-inflammatory genes that control both the

34

Interstitial Cystitis

immune and inflammatory system. The long-range goals of this application are to determine the gene networks involved in bladder responses to BCG therapy. To meet these goals, we will use the mouse as a vehicle for understanding basic biological questions regarding BCG and to permit rigorous control of experimental design. Transgenic mice with reporter genes expressed specifically on endothelial cells (Tie2LacZ) and on promoter elements responsive to NFkappaB (p105-LacZ and p65-LacZ) will be used to address our hypothesis. In addition, the appropriate use of micro array technology combined with subtractive hybridization (SSH) will identify key molecules and mechanisms involved in the transition between acute and chronic inflammation in individual bladder layers. To address our central hypothesis, Aim 1 will quantify the time course alterations in bladder morphology as a consequence of acute and chronic intravesical BCG therapy. Aim 2 will test the hypothesis that NFkB plays a central role on BCG-induced bladder inflammation and Aim 3 will test the hypothesis that acute and chronic instillation of BCG induce a differential gene regulation in bladder mucosa and detrusor muscle. For this purpose, we will use micro array technology combined with suppression subtractive hybridization (SSH) to select bladder mucosa- and detrusor specific genes. Following target validation of SSH-selected genes, a custom array will be developed. This micro array will be used to determine how the bladder transcriptome is altered by BCG therapy. 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 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

Studies

35

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

•

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 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

36

Interstitial Cystitis

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: 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

•

Project Title: CHRONIC PROSTATITIS COLLABORATIVE RESEARCH NETWORK Principal Investigator & Institution: Anderson, Rodney U.; Urology; Stanford University Stanford, Ca 94305

Studies

37

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 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: 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

38

Interstitial Cystitis

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. 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

Studies

39

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 •

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, 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: 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 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

40

Interstitial Cystitis

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 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

Studies

41

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 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

42

Interstitial Cystitis

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 •

Project Title: GENETICS 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 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Interstitial cystitis (IC) comprises severe bladder pain and urinary frequency and urgency, has objective diagnostic findings, and its pathogenesis is unknown. We have shown that first-degree relatives of IC patients have a relative risk of > 16. That this familial aggregation is not solely an environmental effect is reflected by our further findings of significantly greater concordance among monozygotic than dizygotic twins and occurrence of IC in 2nd and 3rd degree relatives who presumably have not shared households. Hypothesizing that alleles for IC are inherited in these families, we will recruit multiplex families, i.e. those with greater than or equal too 2 first degree relatives who meet NIDDK criteria for IC, via a national recruitment campaign directed at urologists, employing the Internet, and collaborating with the Interstitial Cystitis Association. Pedigrees will be constructed with family members assigned to intermediate categories of IC. We will perform linkage analysis seeking loci of susceptibility to IC. We estimate that >900 probands will be evaluated. Reasonable assumptions of eligibility and volunteer rates suggest we will enroll >450 multiplex families with >2400 family members donating DNA. To date, a survey has already identified 101 potential probands; 143 unsolicited, additional potential probands

Studies

43

have contacted us. Parametric, non-parametric, and conditional analyses will be performed with attention to subgroups to maximize homogeneity and to intermediate categories to avoid misclassification. The large number of participants will provide substantial power. We will finely map linkage regions and perform family-based linkage and association tests. In parallel we will help to discover additional multiplex families for extension/replication studies. These data on pedigrees and genotypes and stored DNA, from properly informed participants, will be a valuable resource. The identification of alleles of susceptibility to IC may reveal clues to pathogenesis, clinical therapy, preventive strategy, and possibly gene therapies. 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-Medical 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 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

44

Interstitial Cystitis

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: 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

Studies

•

45

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 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

46

Interstitial Cystitis

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 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)

Studies

47

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 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

•

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

48

Interstitial Cystitis

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 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: 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

Studies

49

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 •

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

•

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

50

Interstitial Cystitis

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 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: 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) 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

Studies

51

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: 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 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 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)

52

Interstitial Cystitis

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 •

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

Studies

53

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 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

•

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 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

54

Interstitial Cystitis

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 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

Studies

55

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: MOUSE MODELS FOR INTERSTITIAL CYSTITIS Principal Investigator & Institution: Schwarz, Edward M.; Associate Professor; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 21-SEP-2001; Project End 31-JUL-2005 Summary: Interstitial Cystitis (IC) is a chronic irritable voiding syndrome of unknown etiology. Urinary frequency, urgency, nocturia, suprapubic pressure, and bladder/pelvic pain characterize this condition and there are no predictably effective treatments. Thus, many suffer with incapacitating symptoms for the rest of their lives. We believe that a small animal model will greatly enhance progress since pathophysiologic mechanisms can be dissected and therapeutic strategies developed in a far more controlled environment than the clinic. A model of IC must display features common to the clinical conditions, including chronicity, key elements of the symptom complex, and common pathophysiologic alterations. One etiologic hypothesis is that an urothelial barrier defect exists permitting urinary constituents unusual access to the tissues of the bladder wall. Whether this is an initiating event or the result of other perturbations is controversial, but most lines of evidence support the existence of a barrier deficiency in the clinical syndrome. To generate a small animal model to test the hypothesis that there is a relationship between a barrier defect and irritable voiding patterns, we have developed quantitative methods to evaluate the interplay of bladder permeability with void volume and frequency in mice. We will monitor plasma fluorescein following intravesical administration to assess the integrity of the bladder permeability barrier. We will use computerized balances to measure void volume and frequency within and across days. We will induce chronic cystitis by continuous exposure of the urothelium to agents that disrupt the bladder lining by implanting indwelling bladder catheter in each mouse. This will allow us to determine the relationship between altered bladder permeability and micturition frequency and volume. We will attempt to prevent and/or reverse these chronic barrier defects with several drugs (heparin, pentosan polysulfate and hyaluronic acid) and see what effect they have on permeability and voiding patterns. Finally, we will attempt to generate a transgenic mouse model of IC by targeting the expression of a secreted form of mouse protamine-1 (sMP1) to the transitional epithelium and evaluate these animals in our system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

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

56

Interstitial Cystitis

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: 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 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

Studies

57

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. 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

58

Interstitial Cystitis

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 •

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 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

Studies

59

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 •

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 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

60

Interstitial Cystitis

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 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

Studies

61

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 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

62

Interstitial Cystitis

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 •

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 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

Studies

63

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 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

64

Interstitial Cystitis

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: REGULATION OF BLADDER NGF BY ESTROGEN Principal Investigator & Institution: Bjorling, Dale E.; Professor and Chair; Surgical Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The incidence of many painful inflammatory disorders is significantly greater in women than in men, and women comprise 90 percent of patients with interstitial cystitis, a painful bladder disorder of uncertain etiology. The severity of symptoms of interstitial cystitis fluctuates with the menstrual cycle and may improve during pregnancy. The proposed research will test the hypothesis that the sex hormone estrogen increases nerve growth factor (NGF) release and uptake in the bladder, thereby predisposing to bladder inflammation and accounting for gender-related differences in the incidence of painful bladder disorders. NGF has been shown to be a potent mediator of pain, particularly pain associated with inflammation. The hypothesis that estrogen regulates bladder NGF is supported by exciting preliminary data indicating that in vivo treatment of mice with an estrogen antagonist significantly reduced bladder NGF mRNA. Estrogen also stimulated increased NGF synthesis in primary cultures of human urothelial cells. Lipopolysaccharide, a proinflammatory component of the cell wall of gram negative bacteria, stimulates increased NGF in the mouse bladder. Thus, while increased bladder NGF in response to estrogen may or may not independently result in inflammation or hyperalgesia, upregulation of NGF by estrogen may augment pain and inflammation in response to inflammatory stimuli. This hypothesis will be tested in intact and ovariectomized mice, using hormone replacement and blockade of the estrogen receptor, as well as mice with a genetic disruption of estrogen receptor alpha (ERKOa), and in primary cultures of human urothelial cells. The mechanisms by which estrogen modulates NGF release by the mouse bladder and cultured human uothelial cells will be investigated in the presence and absence of E. coli lipopolysaccharide. The results of these investigations will provide a better understanding of the role of estrogen in bladder inflammation and should suggest new strategies for prevention or amelioration of pain associated with cystitis. 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

Studies

65

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 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

66

Interstitial Cystitis

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 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 CNF1-

Studies

67

expressing 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 •

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 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

68

Interstitial Cystitis

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 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: SENSORY TESTING IN SUBJECTS WITH INTERSTITIAL CYSTITIS Principal Investigator & Institution: Fitzgerald, Mary P.; Assistant Professor; Ob, Gyn, and Reproductive Med; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Recent insights into the neurobiology of interstitial cystitis (IC) and into mechanisms of visceral pain suggest that, like other visceral pain syndromes, IC may be associated with hyperalgesia of the bladder itself, and central sensitization of pain pathways from the bladder. There also may be increased sensitivity to stimulation of body wall tissues in dermatomes to which bladder pain refers. Advances in our understanding of bladder hyperalgesia to distension and the presence of such altered cutaneous stimulation thresholds will help us to design more elegant and evidence-based treatments for IC. This proposal first describes a simple study to measure sensory aspects of bladder sensation with filling in subjects with IC and in controls. Secondly, the use of a Neurometer as a simple instrument to measure cutaneous thresholds to stimulation at frequencies of 2000Hz, 250 Hz, and 5 Hz is described. Finally, testing for the presence of temporal summation of pain and bladder filling sensations as a measure of centralized sensitization of pain pathways is described. If the results of this psychophysical testing prove to be significantly altered in subjects with IC, simple clinical testing of pelvic referral dermatomes may allow clinicians to assess patients for central sensitization, then design and evaluate treatments accordingly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

69

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

•

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 NF-kappaB 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 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

70

Interstitial Cystitis

•

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

•

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 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

Studies

71

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: 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

•

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

72

Interstitial Cystitis

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 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

Studies

73

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 •

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 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

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.3 3 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

74

Interstitial Cystitis

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

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

•

A collaborative approach to managing interstitial cystitis. Author(s): Slade D, Ratner V, Chalker R. Source: Urology. 1997 May; 49(5A Suppl): 10-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145998&dopt=Abstract

•

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

•

A deficit of chondroitin sulfate proteoglycans on the bladder uroepithelium in interstitial cystitis. Author(s): Hurst RE, Roy JB, Min KW, Veltri RW, Marley G, Patton K, Shackelford DL, Stein P, Parsons CL. Source: Urology. 1996 November; 48(5): 817-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8911536&dopt=Abstract

•

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

•

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

Studies

75

•

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

•

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

•

A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis. Author(s): Bade JJ, Laseur M, Nieuwenburg A, van der Weele LT, Mensink HJ. Source: British Journal of Urology. 1997 February; 79(2): 168-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9052464&dopt=Abstract

•

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

•

A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. Author(s): Korting GE, Smith SD, Wheeler MA, Weiss RM, Foster HE Jr. Source: The Journal of Urology. 1999 February; 161(2): 558-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9915448&dopt=Abstract

•

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

•

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

76

Interstitial Cystitis

•

Absence of bacterial DNA in the bladder of patients with interstitial cystitis. Author(s): Haarala M, Jalava J, Laato M, Kiilholma P, Nurmi M, Alanen A. Source: The Journal of Urology. 1996 November; 156(5): 1843-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8863628&dopt=Abstract

•

Activation of the kallikrein kinin system in interstitial cystitis. Author(s): Rosamilia A, Clements JA, Dwyer PL, Kende M, Campbell DJ. Source: The Journal of Urology. 1999 July; 162(1): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10379755&dopt=Abstract

•

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

•

Altered expression of bladder mast cell growth factor receptor (c-kit) in interstitial cystitis. Author(s): Pang X, Sant G, Theoharides TC. Source: Urology. 1998 June; 51(6): 939-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9609630&dopt=Abstract

•

Alternate occurrence of allergic disease and an unusual form of interstitial cystitis. Author(s): Yamada T, Murayama T, Mita H, Akiyama K, Taguchi H. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 1998 July; 5(4): 329-35; Discussion 335-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9712440&dopt=Abstract

•

An assessment of the use of intravesical potassium in the diagnosis of interstitial cystitis. Author(s): Chambers GK, Fenster HN, Cripps S, Jens M, Taylor D. Source: The Journal of Urology. 1999 September; 162(3 Pt 1): 699-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458346&dopt=Abstract

•

An investigation of the nature of bladder mucosal glycoconjugates and their role in interstitial cystitis. Author(s): Bhavanandan VP, Erickson DR. Source: Indian J Biochem Biophys. 1997 February-April; 34(1-2): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9343952&dopt=Abstract

Studies

77

•

Analysis of long-term Elmiron therapy for interstitial cystitis. Author(s): Hanno PM. Source: Urology. 1997 May; 49(5A Suppl): 93-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146008&dopt=Abstract

•

Analysis of long-term Elmiron therapy for interstitial cystitis. Urology 1997;49(Suppl 5A):93-99. Author(s): Sand PK, Winkler HA. Source: Journal of Women's Health / the Official Publication of the Society for the Advancement of Women's Health Research. 1998 March; 7(2): 268-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9555694&dopt=Abstract

•

Anterior enterocele following cystectomy for intractable interstitial cystitis. Author(s): Anderson J, Carrion R, Ordorica R, Hoffman M, Arango H, Lockhart JL. Source: The Journal of Urology. 1998 June; 159(6): 1868-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9598477&dopt=Abstract

•

Antiproliferative activity is present in bladder but not renal pelvic urine from interstitial cystitis patients. Author(s): Keay S, Warren JW, Zhang CO, Tu LM, Gordon DA, Whitmore KE. Source: The Journal of Urology. 1999 October; 162(4): 1487-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10492242&dopt=Abstract

•

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

•

Associations among cystoscopic and urodynamic findings for women enrolled in the Interstitial Cystitis Data Base (ICDB) Study. Author(s): Nigro DA, Wein AJ, Foy M, Parsons CL, Williams M, Nyberg LM Jr, Landis JR, Cook YL, Simon LJ. Source: Urology. 1997 May; 49(5A Suppl): 86-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146007&dopt=Abstract

•

Associations among cystoscopic findings and symptoms and physical examination findings in women enrolled in the Interstitial Cystitis Data Base (ICDB) Study. Author(s): Messing E, Pauk D, Schaeffer A, Nieweglowski M, Nyberg LM Jr, Landis JR, Cook YL, Simon LJ. Source: Urology. 1997 May; 49(5A Suppl): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146006&dopt=Abstract

78

Interstitial Cystitis

•

Associations among urodynamic findings and symptoms in women enrolled in the Interstitial Cystitis Data Base (ICDB) Study. Author(s): Kirkemo A, Peabody M, Diokno AC, Afanasyev A, Nyberg LM Jr, Landis JR, Cook YL, Simon LJ. Source: Urology. 1997 May; 49(5A Suppl): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146005&dopt=Abstract

•

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

•

Autoantibodies and interstitial cystitis. Author(s): Ochs RL. Source: Clin Lab Med. 1997 September; 17(3): 571-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9316774&dopt=Abstract

•

Bacillus Calmette-Guerin immunotherapy for refractory interstitial cystitis. Author(s): Zeidman EJ, Helfrick B, Pollard C, Thompson IM. Source: Urology. 1994 January; 43(1): 121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284874&dopt=Abstract

•

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

•

Behavioral therapy for the treatment of refractory interstitial cystitis. Author(s): Chaiken DC, Blaivas JG, Blaivas ST. Source: The Journal of Urology. 1993 June; 149(6): 1445-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8501784&dopt=Abstract

•

Benzydamine: a new weapon in the treatment of interstitial cystitis. Author(s): Walsh A. Source: Trans Am Assoc Genitourin Surg. 1976; 68: 43-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1030550&dopt=Abstract

Studies

79

•

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

•

Bladder antibodies in interstitial cystitis. Author(s): Silk MR. Source: The Journal of Urology. 1970 March; 103(3): 307-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5412747&dopt=Abstract

•

Bladder detrusor endometriosis mimicking interstitial cystitis. Author(s): Sircus SI, Sant GR, Ucci AA Jr. Source: Urology. 1988 October; 32(4): 339-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3176223&dopt=Abstract

•

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

•

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

•

Bladder mast cell activation in interstitial cystitis. Author(s): Theoharides TC, Sant GR. Source: Semin Urol. 1991 May; 9(2): 74-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1853017&dopt=Abstract

•

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

80

Interstitial Cystitis

•

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

•

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

•

Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct measurement by transvesical absorption of 99mtechnetiumdiethylenetriaminepentaacetic acid. Author(s): Chelsky MJ, Rosen SI, Knight LC, Maurer AH, Hanno PM, Ruggieri MR. Source: The Journal of Urology. 1994 February; 151(2): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8283521&dopt=Abstract

•

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

•

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

•

Bowel perforation and interstitial cystitis in childhood systemic lupus erythematosus. Author(s): Eberhard A, Shore A, Silverman E, Laxer R. Source: The Journal of Rheumatology. 1991 May; 18(5): 746-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1865424&dopt=Abstract

•

Calcium signaling in cultured human detrusor smooth muscle cells from patients with interstitial cystitis. Author(s): Bouchelouche K, Horn T, Nordling J, Larsen S, Hald T, Bouchelouche P. Source: Urology. 2001 June; 57(6 Suppl 1): 109-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378073&dopt=Abstract

Studies

81

•

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

•

Chlorpactin instillation releases calcitonin gene-related peptide in interstitial cystitis patients. Author(s): Kreder K, Lutgendorf S, Knopf MA, McGillis JP. Source: Urology. 2001 June; 57(6 Suppl 1): 128-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378125&dopt=Abstract

•

Chronic interstitial cystitis and systemic lupus erythematosus in an 8-year-old girl. Author(s): La Manna A, Polito C, Papale MR, Rocco CE, Marte A. Source: Pediatric Nephrology (Berlin, Germany). 1998 February; 12(2): 139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9543374&dopt=Abstract

•

Clinical characteristics support that interstitial cystitis is a heterogeneous syndrome. Author(s): Fall M, Aldenborg F, Johansson S, Peeker R. Source: Urology. 2001 June; 57(6 Suppl 1): 129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378127&dopt=Abstract

•

Clinical highlights of the National Institute of Diabetes and Digestive and Kidney Diseases/Interstitial Cystitis Association scientific conference on interstitial cystitis. Author(s): Hanno PM, Sant GR. Source: Urology. 2001 June; 57(6 Suppl 1): 2-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378041&dopt=Abstract

•

Clinical response to an oral prostaglandin analogue in patients with interstitial cystitis. Author(s): Kelly JD, Young MR, Johnston SR, Keane PF. Source: European Urology. 1998; 34(1): 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9676414&dopt=Abstract

•

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

82

Interstitial Cystitis

•

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

•

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

•

Comparison of cystoscopic and histological findings in patients with suspected interstitial cystitis. Author(s): Denson MA, Griebling TL, Cohen MB, Kreder KJ. Source: The Journal of Urology. 2000 December; 164(6): 1908-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061878&dopt=Abstract

•

Complete transurethral resection of ulcers in classic interstitial cystitis. Author(s): Peeker R, Aldenborg F, Fall M. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 2000; 11(5): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052564&dopt=Abstract

•

Concentrations of specific epithelial growth factors in the urine of interstitial cystitis patients and controls. Author(s): Keay S, Zhang CO, Kagen DI, Hise MK, Jacobs SC, Hebel JR, Gordon D, Whitmore K, Bodison S, Warren JW. Source: The Journal of Urology. 1997 November; 158(5): 1983-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9334654&dopt=Abstract

•

Concordance of interstitial cystitis (IC) in identical twins: preliminary data. Author(s): Warren J, Jackson T, Meyers D, Xu J. Source: Urology. 2001 June; 57(6 Suppl 1): 126. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378120&dopt=Abstract

•

Concordance of interstitial cystitis in monozygotic and dizygotic twin pairs. Author(s): Warren JW, Keay SK, Meyers D, Xu J. Source: Urology. 2001 June; 57(6 Suppl 1): 22-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378045&dopt=Abstract

Studies

83

•

Correlation of symptoms between 2 instruments among interstitial cystitis patients. Author(s): Sirinian E, Payne CK. Source: Urology. 2001 June; 57(6 Suppl 1): 124-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378115&dopt=Abstract

•

Corticotropin-releasing hormone perturbations in interstitial cystitis patients: evidence for abnormal sympathetic activity. Author(s): Dimitrakov J, Tchitalov J, Zlatanov T, Dikov D, Rawadi G. Source: Urology. 2001 June; 57(6 Suppl 1): 128. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378124&dopt=Abstract

•

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

•

Cystistat for the treatment of interstitial cystitis: a 3-year follow-up study. Author(s): Nordling J, Jorgensen S, Kallestrup E. Source: Urology. 2001 June; 57(6 Suppl 1): 123. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378112&dopt=Abstract

•

Cyto-injury factors in urine: a possible mechanism for the development of interstitial cystitis. Author(s): Parsons CL, Bautista SL, Stein PC, Zupkas P. Source: The Journal of Urology. 2000 October; 164(4): 1381-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992419&dopt=Abstract

•

Cytologic examination of urine from patients with interstitial cystitis. Author(s): Dodd LG, Tello J. Source: Acta Cytol. 1998 July-August; 42(4): 923-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9684578&dopt=Abstract

•

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

•

Decreased 3H-thymidine incorporation by human bladder epithelial cells following exposure to urine from interstitial cystitis patients. Author(s): Keay S, Zhang CO, Trifillis AL, Hise MK, Hebel JR, Jacobs SC, Warren JW. Source: The Journal of Urology. 1996 December; 156(6): 2073-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8911393&dopt=Abstract

84

Interstitial Cystitis

•

Decreased expression of a glycoprotein component of bladder surface mucin (GP1) in interstitial cystitis. Author(s): Moskowitz MO, Byrne DS, Callahan HJ, Parsons CL, Valderrama E, Moldwin RM. Source: The Journal of Urology. 1994 February; 151(2): 343-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8283520&dopt=Abstract

•

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

•

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

•

Decreased urinary uronic acid levels in individuals with interstitial cystitis. Author(s): Parsons CL, Hurst RE. Source: The Journal of Urology. 1990 April; 143(4): 690-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2313793&dopt=Abstract

•

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

•

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

•

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

Studies

85

•

Development of collagenous colitis in a cecoplasty of a patient with interstitial cystitis. Author(s): Tucky J, Jass JR, Chambers RM, Cohen RJ. Source: Pathology. 1996 January; 28(1): 105-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8714285&dopt=Abstract

•

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

•

Diagnosis of interstitial cystitis. Author(s): Hanno PM. Source: The Urologic Clinics of North America. 1994 February; 21(1): 63-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284846&dopt=Abstract

•

Diagnosis of interstitial cystitis. Author(s): Hanno P, Levin RM, Monson FC, Teuscher C, Zhou ZZ, Ruggieri M, Whitmore K, Wein AJ. Source: The Journal of Urology. 1990 February; 143(2): 278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2299717&dopt=Abstract

•

Dimethyl sulfoxide does not trigger urine histamine release in interstitial cystitis. Author(s): Stout L, Gerspach JM, Levy SM, Yun SK, Lad PM, Leach GE, Zimmern PE. Source: Urology. 1995 November; 46(5): 653-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7495115&dopt=Abstract

•

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

•

Distinctive ultrastructural pathology of nonulcerative interstitial cystitis: new observations and their potential significance in pathogenesis. Author(s): Elbadawi AE, Light JK. Source: Urologia Internationalis. 1996; 56(3): 137-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8860736&dopt=Abstract

86

Interstitial Cystitis

•

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

•

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

•

Do women with idiopathic sensory urgency have early interstitial cystitis? Author(s): Frazer MI, Haylen BT, Sissons M. Source: British Journal of Urology. 1990 September; 66(3): 274-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2207541&dopt=Abstract

•

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

•

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

•

Effect of long-term oral L-arginine on the nitric oxide synthase pathway in the urine from patients with interstitial cystitis. Author(s): Wheeler MA, Smith SD, Saito N, Foster HE Jr, Weiss RM. Source: The Journal of Urology. 1997 December; 158(6): 2045-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366309&dopt=Abstract

•

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

Studies

87

•

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

•

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

•

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

•

Efficacy of pentosan polysulfate in the treatment of interstitial cystitis: a metaanalysis. Author(s): Hwang P, Auclair B, Beechinor D, Diment M, Einarson TR. Source: Urology. 1997 July; 50(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9218016&dopt=Abstract

•

Electromotive administration of intravesical lidocaine in patients with interstitial cystitis. Author(s): Gurpinar T, Wong HY, Griffith DP. Source: Journal of Endourology / Endourological Society. 1996 October; 10(5): 443-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8905491&dopt=Abstract

•

Electromotive drug administration and hydrodistention for the treatment of interstitial cystitis. Author(s): Riedl CR, Knoll M, Plas E, Pfluger H. Source: Journal of Endourology / Endourological Society. 1998 June; 12(3): 269-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9658301&dopt=Abstract

•

Electromotive drug administration of lidocaine and dexamethasone followed by cystodistension in women with interstitial cystitis. Author(s): Rosamilia A, Dwyer PL, Gibson J. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 1997; 8(3): 142-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9449586&dopt=Abstract

88

Interstitial Cystitis

•

Elevated stress protein in transitional cells exposed to urine from interstitial cystitis patients. Author(s): Ito T, Stein PC, Parsons CL, Schmidt JD. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 1998 September; 5(5): 444-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9781432&dopt=Abstract

•

Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. Author(s): Okragly AJ, Niles AL, Saban R, Schmidt D, Hoffman RL, Warner TF, Moon TD, Uehling DT, Haak-Frendscho M. Source: The Journal of Urology. 1999 February; 161(2): 438-41; Discussion 441-2. Erratum In: J Urol 1999 June; 161(6): 1915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9915421&dopt=Abstract

•

Elevated urinary norepinephrine in interstitial cystitis. Author(s): Stein PC, Torri A, Parsons CL. Source: Urology. 1999 June; 53(6): 1140-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367842&dopt=Abstract

•

Epidemiology of interstitial cystitis. Author(s): Jones CA, Nyberg L. Source: Urology. 1997 May; 49(5A Suppl): 2-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145997&dopt=Abstract

•

Epidemiology of interstitial cystitis. Author(s): Koziol JA. Source: The Urologic Clinics of North America. 1994 February; 21(1): 7-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284848&dopt=Abstract

•

Epidemiology of interstitial cystitis: a population based study. Author(s): Curhan GC, Speizer FE, Hunter DJ, Curhan SG, Stampfer MJ. Source: The Journal of Urology. 1999 February; 161(2): 549-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9915446&dopt=Abstract

•

Epithelial coating techniques in the treatment of interstitial cystitis. Author(s): Parsons CL. Source: Urology. 1997 May; 49(5A Suppl): 100-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146009&dopt=Abstract

Studies

89

•

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

•

Evidence for altered proliferative ability of progenitors of urothelial cells in interstitial cystitis. Author(s): Elgavish A, Pattanaik A, Lloyd K, Reed R. Source: The Journal of Urology. 1997 July; 158(1): 248-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9186369&dopt=Abstract

•

Excretion of fluorescein in the urine of women with interstitial cystitis. Author(s): Buffington CA, Woodworth BE. Source: The Journal of Urology. 1997 September; 158(3 Pt 1): 786-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9258081&dopt=Abstract

•

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

•

Failure of combined supratrigonal cystectomy and Mainz ileocecocystoplasty in intractable interstitial cystitis: is histology and mast cell count a reliable predictor for the outcome of surgery? Author(s): Nielsen KK, Kromann-Andersen B, Steven K, Hald T. Source: The Journal of Urology. 1990 August; 144(2 Pt 1): 255-8; Discussion 258-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2374189&dopt=Abstract

•

Fine-structural evidence for vascular injury in patients with interstitial cystitis. Author(s): Mattila J, Pitkanen R, Vaalasti T, Seppanen J. Source: Virchows Arch a Pathol Anat Histopathol. 1983; 398(3): 347-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6402844&dopt=Abstract

•

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

90

Interstitial Cystitis

•

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

•

Further experience with intravesical dimethyl sulfoxide in the treatment of interstitial cystitis. Author(s): Stewart BH, Shirley SW. Source: The Journal of Urology. 1976 July; 116(1): 36-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=933285&dopt=Abstract

•

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

•

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

•

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

•

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

•

Histamine and mucosal mast cells in interstitial cystitis. Author(s): Enerback L, Fall M, Aldenborg F. Source: Agents Actions. 1989 April; 27(1-2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2750582&dopt=Abstract

Studies

91

•

Histamine content and mast cell count of detrusor muscle in patients with interstitial cystitis and other types of chronic cystitis. Author(s): Kastrup J, Hald T, Larsen S, Nielsen VG. Source: British Journal of Urology. 1983 October; 55(5): 495-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6626895&dopt=Abstract

•

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

•

Hydroxyzine for interstitial cystitis. Author(s): Theoharides TC. Source: The Journal of Allergy and Clinical Immunology. 1993 February; 91(2): 686-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8436783&dopt=Abstract

•

Hydroxyzine in the treatment of interstitial cystitis. Author(s): Theoharides TC. Source: The Urologic Clinics of North America. 1994 February; 21(1): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284834&dopt=Abstract

•

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

•

Immunologic and neurobiologic characteristics support that interstitial cystitis is a heterogeneous syndrome. Author(s): Peeker R, Aldenborg F, Dahlstrom A, Enerback L, Haglid K, Johansson SL, Ya-Li J, Rosengren L, Fall M. Source: Urology. 2001 June; 57(6 Suppl 1): 130. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378128&dopt=Abstract

•

Incidence of Helicobacter pylori in patients with interstitial cystitis. Author(s): Haq A, Mattocks S, Wong L, Dasgupta P, Dawson C, Blackford HN, Sharma S, Turner AG. Source: European Urology. 2001 December; 40(6): 652-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805412&dopt=Abstract

92

Interstitial Cystitis

•

Increased urinary excretion of leukotriene E(4) in patients with interstitial cystitis. Author(s): Bouchelouche K, Kristensen B, Nordling J, Horn T, Larsen S, Hald T, Bouchelouche P. Source: Urology. 2001 June; 57(6 Suppl 1): 128. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378123&dopt=Abstract

•

Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis. Author(s): Bouchelouche K, Kristensen B, Nordling J, Horn T, Bouchelouche P. Source: The Journal of Urology. 2001 December; 166(6): 2121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696719&dopt=Abstract

•

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

•

Interstitial cystitis in males. Author(s): Indudhara R, Kubricht W, Lloyd K. Source: Urology. 2001 June; 57(6 Suppl 1): 120-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378105&dopt=Abstract

•

Interstitial cystitis. Author(s): Warren JW, Keay SK. Source: Current Opinion in Urology. 2002 January; 12(1): 69-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753137&dopt=Abstract

•

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

•

Interstitial cystitis: a chronic inflammatory bladder condition. Author(s): Ratner V. Source: World Journal of Urology. 2001 June; 19(3): 157-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469601&dopt=Abstract

Studies

93

•

Interstitial cystitis: a guide to recognition, evaluation, and management for nurse practitioners. Author(s): Gray M, Albo M, Huffstutler S. Source: Journal of Wound, Ostomy, and Continence Nursing : Official Publication of the Wound, Ostomy and Continence Nurses Society / Wocn. 2002 March; 29(2): 93-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901418&dopt=Abstract

•

Interstitial cystitis: a pathophysiology and treatment update. Author(s): Moldwin RM, Sant GR. Source: Clinical Obstetrics and Gynecology. 2002 March; 45(1): 259-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862078&dopt=Abstract

•

Interstitial cystitis: a proposal on cardinal symptoms and signs. Author(s): Mortensen S, Nordling J, Horn T, Hald T; Copenhagen Interstitial Cystitis Study Group. 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=11378110&dopt=Abstract

•

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

•

Interstitial cystitis: epidemiology and clinical presentation. Author(s): Parsons CL. Source: Clinical Obstetrics and Gynecology. 2002 March; 45(1): 242-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862076&dopt=Abstract

•

Interstitial cystitis: urgency and frequency syndrome. Author(s): Metts JF. Source: American Family Physician. 2001 October 1; 64(7): 1199-206. Review. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601802&dopt=Abstract

•

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

94

Interstitial Cystitis

•

Interstitial cystitis--a time for revision of name and diagnostic criteria in the new millennium? Author(s): Peeker R, Fall M. Source: Bju International. 2002 April; 89(6): 637-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942986&dopt=Abstract

•

Interstitial cystitis--a time for revision of name and diagnostic criteria in the new millennium? Author(s): Agarwal M, O'Reilly PH, Dixon RA. Source: Bju International. 2001 September; 88(4): 348-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564019&dopt=Abstract

•

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

•

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

•

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

•

Laser therapy for interstitial cystitis. Author(s): Malloy TR, Shanberg AM. Source: The Urologic Clinics of North America. 1994 February; 21(1): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284837&dopt=Abstract

•

Letter: Interstitial cystitis. Author(s): Pollen JJ. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1976 February 7; 50(6): 159. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1257849&dopt=Abstract

Studies

95

•

Leukocyte chemotactic factors in interstitial cystitis: a possible biological marker of the disease. Author(s): Walzak MP Jr, Elgebaly SA, Allam ME, Oselinsky D. Source: Semin Urol. 1991 May; 9(2): 131-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1853010&dopt=Abstract

•

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

•

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

•

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

•

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

•

Long-term results of cystolysis (supratrigonal denervation) of the bladder for intractable interstitial cystitis. Author(s): Albers DD, Geyer JR. Source: The Journal of Urology. 1988 June; 139(6): 1205-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3373588&dopt=Abstract

•

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

96

Interstitial Cystitis

•

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

•

Lumbar epidural blockade for management of pain in interstitial cystitis. Author(s): Irwin PP, Hammonds WD, Galloway NT. Source: British Journal of Urology. 1993 April; 71(4): 413-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8499984&dopt=Abstract

•

Lumbar nerve root compression and interstitial cystitis--response to decompressive surgery. Author(s): Gillespie L, Bray R, Levin N, Delamarter R. Source: British Journal of Urology. 1991 October; 68(4): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1933154&dopt=Abstract

•

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

•

Lymphocyte function in patients with interstitial cystitis. Author(s): Miller CH, MacDermott JP, Quattrocchi KB, Broderick GA, Stone AR. Source: The Journal of Urology. 1992 March; 147(3): 592-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1538435&dopt=Abstract

•

Lymphocyte sub-populations in the bladder wall in normal bladder, bacterial cystitis and interstitial cystitis. Author(s): Christmas TJ. Source: British Journal of Urology. 1994 May; 73(5): 508-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8012772&dopt=Abstract

•

Management of interstitial cystitis with ileocecocystoplasty. Author(s): Wallack H, Lome LG, Presman D. Source: Urology. 1975 January; 5(1): 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1114546&dopt=Abstract

•

Massive extracellular tryptase from activated bladder mast cells in interstitial cystitis. Author(s): Am Fam Physician. 2001 Oct 1;64(7):1212-4 Source: Urology. 2001 October; 58(4): 605-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11601803

Studies

97

•

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

•

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

•

Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis. Author(s): Kisman OK, Lycklama a Nijeholt AA, van Krieken JH. Source: The Journal of Urology. 1991 October; 146(4): 1113-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1895435&dopt=Abstract

•

Mast cell involvement in interstitial cystitis. Author(s): Lynes WL, Flynn SD, Shortliffe LD, Lemmers M, Zipser R, Roberts LJ 2nd, Stamey TA. Source: The Journal of Urology. 1987 October; 138(4): 746-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3477649&dopt=Abstract

•

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

•

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

•

Mast cells in interstitial cystitis. Author(s): Aldenborg F, Fall M, Enerback L. Source: Annales D'urologie. 1989; 23(2): 165-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2472770&dopt=Abstract

98

Interstitial Cystitis

•

Mast cells in interstitial cystitis. Author(s): Larsen S, Thompson SA, Hald T, Barnard RJ, Gilpin CJ, Dixon JS, Gosling JA. Source: British Journal of Urology. 1982 June; 54(3): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7104591&dopt=Abstract

•

Measurement of symptoms of interstitial cystitis. A pilot study. Author(s): Keller ML, McCarthy DO, Neider RS. Source: The Urologic Clinics of North America. 1994 February; 21(1): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284847&dopt=Abstract

•

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

•

Medical treatment of interstitial cystitis (other than Rimso-50/Elmiron). Author(s): Hanno PM, Wein AJ. Source: Urology. 1987 April; 29(4 Suppl): 22-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2436377&dopt=Abstract

•

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

•

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

•

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

•

Mycoplasma hominis and interstitial cystitis. Author(s): Hedelin HH, Mardh PA, Brorson JE, Fall M, Moller BR, Pettersson KG. Source: Sexually Transmitted Diseases. 1983 October-December; 10(4 Suppl): 327-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6665676&dopt=Abstract

Studies

99

•

Nalmefene in the treatment of interstitial cystitis. Author(s): Stone NN. Source: The Urologic Clinics of North America. 1994 February; 21(1): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284832&dopt=Abstract

•

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

•

Nephrogenic adenoma associated with interstitial cystitis. Author(s): Plimpton HW, Crawford ED, Goldhaln RT. Source: Urology. 1985 November; 26(5): 498-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4060396&dopt=Abstract

•

Nerve fibre proliferation in interstitial cystitis. Author(s): Christmas TJ, Rode J, Chapple CR, Milroy EJ, Turner-Warwick RT. Source: Virchows Arch a Pathol Anat Histopathol. 1990; 416(5): 447-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2107633&dopt=Abstract

•

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

•

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

•

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

•

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

100 Interstitial Cystitis

•

Novel complications with HTLV-1-associated myelopathy/tropical spastic paraparesis: interstitial cystitis and persistent prostatitis. Author(s): Nomata K, Nakamura T, Suzu H, Yushita Y, Kanetake H, Sawada T, Ikeda S, Hino S, Nagataki S, Saito Y. Source: Japanese Journal of Cancer Research : Gann. 1992 June; 83(6): 601-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1353753&dopt=Abstract

•

Observations on interstitial cystitis. Author(s): Lapides J. Source: Urology. 1975 May; 5(5): 610-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1129888&dopt=Abstract

•

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

•

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

•

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

•

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

•

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

Studies

101

•

Origin of pain in interstitial cystitis. Effect of ultrasound treatment on the concomitant levator ani spasm syndrome. Author(s): Lilius HG, Oravisto KJ, Valtonen EJ. Source: Scandinavian Journal of Urology and Nephrology. 1973; 7(2): 150-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4759775&dopt=Abstract

•

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

•

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

•

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

•

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

•

Parallel pathologies? Vulvar vestibulitis and interstitial cystitis. Author(s): Stewart EG, Berger BM. Source: J Reprod Med. 1997 March; 42(3): 131-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9109078&dopt=Abstract

•

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

102 Interstitial Cystitis

•

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

•

Pentosanpolysulphate for interstitial cystitis. Author(s): Barrington JW, Stephenson TP. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 1997; 8(5): 293-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9557994&dopt=Abstract

•

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

•

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

•

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

•

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

•

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

Studies

103

•

Polymerase chain reaction amplification of bacterial 16S rRNA genes in interstitial cystitis and control patient bladder biopsies. Author(s): Keay S, Zhang CO, Baldwin BR, Jacobs SC, Warren JW. Source: The Journal of Urology. 1998 January; 159(1): 280-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9400495&dopt=Abstract

•

Postmenopausal cystitis. Bladder cancer may be a cause, but interstitial cystitis is an unusual differential diagnosis. Author(s): Turner W, Eardley I, Joyce AD, Harnden P. Source: Bmj (Clinical Research Ed.). 1996 October 26; 313(7064): 1079. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8898610&dopt=Abstract

•

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

•

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

•

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

•

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

•

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

104 Interstitial Cystitis

•

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

•

Psychometric analysis of the University of Wisconsin Interstitial Cystitis Scale: implications for use in randomized clinical trials. Author(s): Goin JE, Olaleye D, Peters KM, Steinert B, Habicht K, Wynant G. Source: The Journal of Urology. 1998 March; 159(3): 1085-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9474236&dopt=Abstract

•

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

•

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

•

Questions about interstitial cystitis. Author(s): Keyes DP. Source: The American Journal of Nursing. 1986 May; 86(5): 533. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3635358&dopt=Abstract

•

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

•

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

Studies

105

•

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

•

Re: Diagnosis of interstitial cystitis. Author(s): Fugazzotto P. Source: The Journal of Urology. 1993 July; 150(1): 199-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8510254&dopt=Abstract

•

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

•

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

•

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

•

Re: Mast cell counts are not useful in the diagnosis of nonulcerative interstitial cystitis. Author(s): Sant GR, Theoharides TC. Source: The Journal of Urology. 1996 October; 156(4): 1445-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8808900&dopt=Abstract

•

Re: Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis. Author(s): MacDermott JP, Stone AR. Source: The Journal of Urology. 1993 February; 149(2): 379. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8481207&dopt=Abstract

106 Interstitial Cystitis

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Studies

107

•

Recurrent interstitial cystitis following cystoplasty: fact or fiction? Author(s): MacDermott JP, Charpied GL, Tesluk H, Stone AR. Source: The Journal of Urology. 1990 July; 144(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2359178&dopt=Abstract

•

Rediscovering a “rare” disease: a patient's perspective on interstitial cystitis. Author(s): Ratner V. Source: Urology. 1987 April; 29(4 Suppl): 44-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3564235&dopt=Abstract

•

Results of treatment of refractory interstitial cystitis with intravesical hyaluronic acid. Author(s): Porru D, Campus G, Tudino D, Valdes E, Vespa A, Scarpa RM, Usai E. Source: Urologia Internationalis. 1997; 59(1): 26-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9313320&dopt=Abstract

•

Role of the immune response in interstitial cystitis. Author(s): Theoharides TC, Sant GR. Source: Clinical Immunology and Immunopathology. 1995 October; 77(1): 115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7554476&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

•

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

•

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

•

Scanning electron microscopic findings in interstitial cystitis. Author(s): Anderstrom CR, Fall M, Johansson SL. Source: British Journal of Urology. 1989 March; 63(3): 270-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2702424&dopt=Abstract

108 Interstitial Cystitis

•

Search for mycobacteria in interstitial cystitis using mycobacteria-specific DNA probes with signal amplification by polymerase chain reaction. Author(s): Hampson SJ, Christmas TJ, Moss MT. Source: British Journal of Urology. 1993 September; 72(3): 303-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8220991&dopt=Abstract

•

Self-care effectiveness and health outcomes in women with interstitial cystitis: implications for mental health clinicians. Author(s): Webster DC, Brennan T. Source: Issues in Mental Health Nursing. 1998 September-October; 19(5): 495-519. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9782865&dopt=Abstract

•

Self-care regimens for patients with interstitial cystitis. Author(s): Whitmore KE. Source: The Urologic Clinics of North America. 1994 February; 21(1): 121-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284835&dopt=Abstract

•

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

•

Severe interstitial cystitis caused by tiaprofenic acid. Author(s): Gheyi SK, Robertson A, Atkinson PM. Source: Journal of the Royal Society of Medicine. 1999 January; 92(1): 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10319030&dopt=Abstract

•

Sex and interstitial cystitis: explaining the pain and planning self-care. Author(s): Webster DC. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 1993 March; 13(1): 4-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8451661&dopt=Abstract

•

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

Studies

109

•

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

•

Sjogren's syndrome in patients with interstitial cystitis. Author(s): Van de Merwe J, Kamerling R, Arendsen E, Mulder D, Hooijkaas H. Source: The Journal of Rheumatology. 1993 June; 20(6): 962-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8350331&dopt=Abstract

•

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

•

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

•

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

•

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

•

Surgical management of interstitial cystitis. Author(s): Irwin PP, Galloway NT. Source: The Urologic Clinics of North America. 1994 February; 21(1): 145-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284838&dopt=Abstract

110 Interstitial Cystitis

•

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

•

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

•

The association of elevated urinary total to sulfated glycosaminoglycan ratio and high molecular mass hyaluronic acid with interstitial cystitis. Author(s): Wei DC, Politano VA, Selzer MG, Lokeshwar VB. Source: The Journal of Urology. 2000 May; 163(5): 1577-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751891&dopt=Abstract

•

The comparison of clinical and histopathologic features of interstitial cystitis. Author(s): Hanus T, Zamecnik L, Jansky M, Jarolim L, Povysil C, Benett R. 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=11378131&dopt=Abstract

•

The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis. Author(s): Bouchelouche K, Nordling J, Hald T, Bouchelouche P. Source: The Journal of Urology. 2001 November; 166(5): 1734-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586212&dopt=Abstract

•

The effect of manual physical therapy in patients diagnosed with interstitial cystitis, high-tone pelvic floor dysfunction, and sacroiliac dysfunction. Author(s): Lukban J, Whitmore K, Kellogg-Spadt S, Bologna R, Lesher A, Fletcher E. Source: Urology. 2001 June; 57(6 Suppl 1): 121-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378106&dopt=Abstract

•

The efficacy of calcium glycerophosphate in the prevention of food-related flares in interstitial cystitis. Author(s): Bologna RA, Gomelsky A, Lukban JC, Tu LM, Holzberg AS, Whitmore KE. Source: Urology. 2001 June; 57(6 Suppl 1): 119-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378102&dopt=Abstract

Studies

111

•

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

•

The efficacy of intravesical bacillus Calmette-Guerin in the treatment of interstitial cystitis: long-term followup. Author(s): Peters KM, Diokno AC, Steinert BW, Gonzalez JA. Source: The Journal of Urology. 1998 May; 159(5): 1483-6; Discussion 1486-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554338&dopt=Abstract

•

The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial. Author(s): Peters K, Diokno A, Steinert B, Yuhico M, Mitchell B, Krohta S, Gillette B, Gonzalez J. Source: The Journal of Urology. 1997 June; 157(6): 2090-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146587&dopt=Abstract

•

The epidemiology of interstitial cystitis: is it time to expand our definition? Author(s): Kusek JW, Nyberg LM. Source: Urology. 2001 June; 57(6 Suppl 1): 95-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378056&dopt=Abstract

•

The incidence of Helicobacter pylori in patients with interstitial cystitis. Author(s): English SF, Liebert M, Cross CA, McGuire EJ. Source: The Journal of Urology. 1998 March; 159(3): 772-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9474145&dopt=Abstract

•

The Interstitial Cystitis Data Base Study: concepts and preliminary baseline descriptive statistics. Author(s): Simon LJ, Landis JR, Erickson DR, Nyberg LM. Source: Urology. 1997 May; 49(5A Suppl): 64-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146004&dopt=Abstract

•

The pain of interstitial cystitis. Author(s): Dwyer PL, Rosamilia A. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 1997; 8(5): 263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9557988&dopt=Abstract

112 Interstitial Cystitis

•

The psychosocial economic impact of invisible chronic disease: examining the experience of patients with interstitial cystitis. Author(s): Azevedo K, Payne CK. Source: Urology. 2001 June; 57(6 Suppl 1): 118. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378097&dopt=Abstract

•

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

•

The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. Author(s): Parsons CL, Greenberger M, Gabal L, Bidair M, Barme G. Source: The Journal of Urology. 1998 June; 159(6): 1862-6; Discussion 1866-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9598476&dopt=Abstract

•

The treatment of interstitial cystitis with supratrigonal cystectomy and ileocystoplasty: difference in outcome between classic and nonulcer disease. Author(s): Peeker R, Aldenborg F, Fall M. Source: The Journal of Urology. 1998 May; 159(5): 1479-82. Erratum In: J Urol 1998 July; 160(1): 136. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554337&dopt=Abstract

•

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

•

Treatment of interstitial cystitis with montelukast, a leukotriene D(4) receptor antagonist. Author(s): Bouchelouche K, Nordling J, Hald T, Bouchelouche P. Source: Urology. 2001 June; 57(6 Suppl 1): 118. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378098&dopt=Abstract

•

Treatment of interstitial cystitis: comparison of subtrigonal and supratrigonal cystectomy combined with orthotopic bladder substitution. Author(s): Linn JF, Hohenfellner M, Roth S, Dahms SE, Stein R, Hertle L, Thuroff JW, Hohenfellner R. Source: The Journal of Urology. 1998 March; 159(3): 774-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9474146&dopt=Abstract

Studies

113

•

Treatment of refractory interstitial cystitis. Author(s): Morales A, Emerson L, Nickel JC. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 1996; 7(4): 215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895807&dopt=Abstract

•

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

•

Urinary chondroitin sulfates, heparan sulfate and total sulfated glycosaminoglycans in interstitial cystitis. Author(s): Erickson DR, Ordille S, Martin A, Bhavanandan VP. Source: The Journal of Urology. 1997 January; 157(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8976216&dopt=Abstract

•

Urinary epitectin (MUC-1 glycoprotein) in the menstrual cycle and interstitial cystitis. Author(s): Erickson DR, Mast S, Ordille S, Bhavanandan VP. Source: The Journal of Urology. 1996 September; 156(3): 938-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8709368&dopt=Abstract

•

Urinary glycosaminoglycan excretion as a laboratory marker in the diagnosis of interstitial cystitis. Author(s): Hurst RE, Parsons CL, Roy JB, Young JL. Source: The Journal of Urology. 1993 January; 149(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8417212&dopt=Abstract

•

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

•

Urinary neutrophil chemotactic factors in interstitial cystitis patients and a rabbit model of bladder inflammation. Author(s): Elgebaly SA, Allam ME, Walzak MP Jr, Oselinsky D, Gillies C, Yamase H. Source: The Journal of Urology. 1992 May; 147(5): 1382-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1569692&dopt=Abstract

114 Interstitial Cystitis

•

Urinary nitric oxide synthase activity and cyclic GMP levels are decreased with interstitial cystitis and increased with urinary tract infections. Author(s): Smith SD, Wheeler MA, Foster HE Jr, Weiss RM. Source: The Journal of Urology. 1996 April; 155(4): 1432-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8632605&dopt=Abstract

•

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

•

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

•

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

•

Urodynamic findings in interstitial cystitis. Author(s): Steinkohl WB, Leach GE. Source: Urology. 1989 December; 34(6): 399-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2595888&dopt=Abstract

•

Urodynamic findings in interstitial cystitis. Author(s): Kuo HC, Chang SC, Hsu T. Source: J Formos Med Assoc. 1992 July; 91(7): 694-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1360297&dopt=Abstract

•

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

Studies

115

•

Urodynamic studies in interstitial cystitis. Author(s): Perez-Marrero R, Emerson L, Juma S. Source: Urology. 1987 April; 29(4 Suppl): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3564230&dopt=Abstract

•

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

•

Use and effectiveness of physical self-care strategies for interstitial cystitis. Author(s): Webster DC, Brennan T. Source: The Nurse Practitioner. 1994 October; 19(10): 55-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7529390&dopt=Abstract

•

Use and effectiveness of psychological self-care strategies for interstitial cystitis. Author(s): Webster DC, Brennan T. Source: Health Care for Women International. 1995 September-October; 16(5): 463-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8576017&dopt=Abstract

•

Use and effectiveness of sexual self-care strategies for interstitial cystitis. Author(s): Webster DC, Brennan T. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 1995 March; 15(1): 14-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7792618&dopt=Abstract

•

Use of amitriptyline in the treatment of interstitial cystitis. Author(s): Hanno PM, Buehler J, Wein AJ. Source: The Journal of Urology. 1989 April; 141(4): 846-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2926877&dopt=Abstract

•

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

•

Vascular immunopathology in interstitial cystitis. Author(s): Mattila J. Source: Clinical Immunology and Immunopathology. 1982 June; 23(3): 648-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6981479&dopt=Abstract

116 Interstitial Cystitis

•

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

117

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

Finding Nutrition Studies on Interstitial 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.4 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “interstitial cystitis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

118 Interstitial Cystitis

The following information is typical of that found when using the “Full IBIDS Database” to search for “interstitial 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

•

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

•

Adverse reactions to tiaprofenic acid mimicking interstitial cystitis. Author(s): Department of Urology, Freeman Hospital, Newcastle Upon Tyne. Source: Harrison, W J Willis, R G Neal, D E BMJ. 1994 September 3; 309(6954): 574 09598138

•

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

•

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

•

Clinical response to an oral prostaglandin analogue in patients with interstitial cystitis. Author(s): Department of Urology, Belfast City Hospital, Northern Ireland. Source: Kelly, J D Young, M R Johnston, S R Keane, P F Eur-Urol. 1998; 34(1): 53-6 03022838

•

Effect of long-term oral L-arginine on the nitric oxide synthase pathway in the urine from patients with interstitial cystitis. Author(s): Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA. Source: Wheeler, M A Smith, S D Saito, N Foster, H E Weiss, R M J-Urol. 1997 December; 158(6): 2045-50 0022-5347

•

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

•

Effects of resiniferatoxin on the neurogenic component of feline interstitial cystitis. Author(s): Department of Veterinary Clinical Sciences, Ohio State University, Columbus, Ohio, USA.

Nutrition

119

Source: March, P Teng, B Westropp, J Buffington, T Urology. 2001 June; 57(6 Suppl 1): 114 1527-9995 •

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

•

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

•

Gynecologic presentation of interstitial cystitis as detected by intravesical potassium sensitivity. Author(s): Division of Urology, University of California, San Diego Medical Center, San Diego, California 92103-8897, USA. Source: Parsons, C L Bullen, M Kahn, B S Stanford, E J Willems, J J Obstet-Gynecol. 2001 July; 98(1): 127-32 0029-7844

•

Immunofluorescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis. Author(s): Women's Clinic for Interstitial Cystitis, Beverly Hills, California. Source: Gillespie, L Said, J Sostrin, S Kleiwer, K Br-J-Urol. 1990 September; 66(3): 265-73 0007-1331

•

Interstitial cystitis and the potential role of gabapentin. Author(s): Pain Relief Centers, PA, Hickory, NC, USA. Source: Hansen, H C South-Med-J. 2000 February; 93(2): 238-42 0038-4348

•

Is the diet of patients with interstitial cystitis related to their disease? Author(s): Department of Urology, St. Anna Hospital, Oss, The Netherlands. Source: Bade, J J Peeters, J M Mensink, H J Eur-Urol. 1997; 32(2): 179-83 0302-2838

•

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

•

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

•

New agents for the medical treatment of interstitial cystitis. Author(s): Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. [email protected] Source: Theoharides, T C Sant, G R Expert-Opin-Investig-Drugs. 2001 March; 10(3): 52146 1354-3784

•

Parallel pathologies? Vulvar vestibulitis and interstitial cystitis. Author(s): Stewart-Forbes Specialty Service, Harvard Pilgrim Health Care, Boston, Massachusetts, USA. Source: Stewart, E G Berger, B M J-Reprod-Med. 1997 March; 42(3): 131-4 0024-7758

120 Interstitial Cystitis

•

Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis. Author(s): Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts, USA. Source: Chiang, G Patra, P Letourneau, R Jeudy, S Boucher, W Green, M Sant, G R Theoharides, T C J-Urol. 2000 December; 164(6): 2119-25 0022-5347

•

Potassium leak test predicts outcome in interstitial cystitis. Author(s): Division of Urology, University of Texas Health Science Center, San Antonio, USA. Source: Teichman, J M Nielsen Omeis, B J J-Urol. 1999 June; 161(6): 1791-4; discussion 1794-6 0022-5347

•

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

•

Severe interstitial cystitis caused by tiaprofenic acid. Author(s): Department of Urology, Darlington Memorial Hospital, County Durham, UK. Source: Gheyi, S K Robertson, A Atkinson, P M J-R-Soc-Med. 1999 January; 92(1): 17 0141-0768

•

Successful therapy of interstitial cystitis with pentosanpolysulfate. Source: Parsons, C L Mulholland, S G J-Urol. 1987 September; 138(3): 513-6 0022-5347

•

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

•

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

•

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

•

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

•

Urinary chondroitin sulfates, heparan sulfate and total sulfated glycosaminoglycans in interstitial cystitis. Author(s): Department of Surgery (Division of Urology), Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, USA. Source: Erickson, D R Ordille, S Martin, A Bhavanandan, V P J-Urol. 1997 January; 157(1): 61-4 0022-5347

Nutrition

121

•

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

•

Use and effectiveness of physical self-care strategies for interstitial cystitis. Author(s): School of Nursing, University of Colorado Health Sciences Center, Denver. Source: Webster, D C Brennan, T Nurse-Pract. 1994 October; 19(10): 55-61 0361-1817

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

•

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

•

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

•

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

•

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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

122 Interstitial Cystitis

•

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

•

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

•

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

123

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

A study of 9-nitrocamptothecin (RFS-2000) in patients with advanced pancreatic cancer. Author(s): Stehlin JS, Giovanella BC, Natelson EA, De Ipolyi PD, Coil D, Davis B, Wolk D, Wallace P, Trojacek A. Source: International Journal of Oncology. 1999 May; 14(5): 821-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200331&dopt=Abstract

•

Arginine: Clinical potential of a semi-essential amino. Author(s): Appleton J. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 December; 7(6): 512-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495375&dopt=Abstract

124 Interstitial Cystitis

•

Beating the burn. Author(s): Brett H, Barker S. Source: Nurs Times. 1998 August 12-18; 94(32): 75-6, 79. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9752188&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

•

Characteristics of women with vulvar pain disorders: responses to a Web-based survey. Author(s): Gordon AS, Panahian-Jand M, Mccomb F, Melegari C, Sharp S. Source: Journal of Sex & Marital Therapy. 2003; 29 Suppl 1: 45-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735088&dopt=Abstract

•

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

•

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

•

Electric stimulation and urinary incontinence: research and alternatives. Author(s): Moore KN, Gray M, Rayome R. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 1995 September; 15(3): 94-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7481893&dopt=Abstract

•

Empowering the patient: hypnosis in the management of cancer, surgical disease and chronic pain. Author(s): Lynch DF Jr. Source: Am J Clin Hypn. 1999 October; 42(2): 122-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10624023&dopt=Abstract

•

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.

Alternative Medicine 125

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 •

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

•

Hatha Yoga therapy management of urologic disorders. Author(s): Ripoll E, Mahowald D. Source: World Journal of Urology. 2002 November; 20(5): 306-9. Epub 2002 October 24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522587&dopt=Abstract

•

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

•

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

•

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

•

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

126 Interstitial Cystitis

•

Musculoskeletal pelvic pain in a pediatric and adolescent gynecology practice Author(s): Schroeder B, Sanfilippo JS, Hertweck SP. Source: Journal of Pediatric and Adolescent Gynecology. 2000 May; 13(2): 90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10869976&dopt=Abstract

•

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

•

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

•

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

•

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

•

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

•

Sulfur in human nutrition and applications in medicine. Author(s): Parcell S.

Alternative Medicine 127

Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 February; 7(1): 22-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896744&dopt=Abstract •

TENS: a treatment option for bladder dysfunction. Author(s): Bristow SE, Hasan ST, Neal DE. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 1996; 7(4): 185-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895802&dopt=Abstract

•

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

•

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

•

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

•

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

•

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

•

Transcutaneous electrical nerve stimulation in interstitial cystitis. Update on clinical experience. Author(s): Fall M.

128 Interstitial Cystitis

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 •

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

•

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

•

Urge incontinence in women. Author(s): Ingelman-Sundberg A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1975; 54(2): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1136720&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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Alternative Medicine 129

The following is a specific Web list relating to interstitial 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 Prostatitis Source: Healthnotes, Inc.; www.healthnotes.com

•

Herbs and Supplements Arginine Source: Healthnotes, Inc.; www.healthnotes.com DMSO Source: Healthnotes, Inc.; www.healthnotes.com MSM Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,807,00.html

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.

131

CHAPTER 4. DISSERTATIONS ON INTERSTITIAL CYSTITIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to interstitial cystitis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “interstitial cystitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on interstitial cystitis, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Interstitial Cystitis ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to interstitial cystitis. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Development of Adapted Yoga Program for Symptom Relief of Chronic Pelvic Pain Syndrome with Plans for Implementation and Evaluation by Gross, Wendy Lou; EDD from Nova Southeastern University, 2002 http://wwwlib.umi.com/dissertations/fullcit/f626689

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

133

CHAPTER 5. CLINICAL TRIALS AND INTERSTITIAL CYSTITIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning interstitial cystitis.

Recent Trials on Interstitial Cystitis The following is a list of recent trials dedicated to interstitial cystitis.5 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

•

Phase I/II Randomized, Placebo-Controlled Study of Capsaicin for Interstitial Cystitis and Vulvar Vestibulitis Condition(s): Interstitial Cystitis; Vulvar Diseases Study Status: This study is no longer recruiting patients.

5

These are listed at www.ClinicalTrials.gov.

134 Interstitial Cystitis

Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Pittsburgh Purpose - Excerpt: Objectives: I. Estimate the optimal safe dose of intravesical capsaicin in patients with interstitial cystitis. II. Evaluate the efficacy of 0.025% topical capsaicin in relieving chronic burning pain in patients with vulvar vestibulitis. III. Evaluate the effect of capsaicin on type C nerve fibers in bladder mucosa and vulvar skin. IV. Evaluate the effect of C fiber depletion on urinary levels of histamine and prostaglandin. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004316

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 “interstitial 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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Clinical Trials 135

•

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/

•

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

•

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

•

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

•

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

•

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

•

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

137

CHAPTER 6. PATENTS ON INTERSTITIAL 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.6 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “interstitial cystitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on interstitial cystitis, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Interstitial Cystitis By performing a patent search focusing on interstitial 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 will tell you how to obtain this information later in the chapter. 6Adapted

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

138 Interstitial Cystitis

The following is an example of the type of information that you can expect to obtain from a patent search on interstitial 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__

•

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 composition containing cromolyn sodium in effective amount is applied to the vaginal vestibule area, with the application repeated as necessary to effectively address the

Patents 139

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 cultures (1) percentage of single cells and percentage of large colonies; (2) determining proliferative ability; (3) determining differentiation ability; (4) determining the

140 Interstitial Cystitis

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 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

Patents 141

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__ •

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

142 Interstitial Cystitis

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__ •

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

Patents 143

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 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

144 Interstitial Cystitis

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 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 for diagnosing and treating chronic pelvic pain syndrome Inventor(s): Alexander; Richard B. (Ellicott City, MD), Ponniah; Sathibalan (Ellicott City, MD) Assignee(s): University of Maryland, Baltimore (Baltimore, MD) Patent Number: 6,180,355 Date filed: May 7, 1999 Abstract: The present invention provides a superior method of diagnosing Chronic Pelvic Pain Syndrome in men comprising measuring levels of cytokines in semen or components or fractions of semen. The invention also provides a method of treating a condition associated with elevated levels of a cytokine, such as TNF-.alpha., in semen or a component or fraction thereof, comprising administering a therapeutically effective

Patents 145

amount of an ant-cytokine compound or composition, such as an anti-TNF-.alpha. compound or composition. Excerpt(s): Chronic prostatitis/chronic pelvic pain syndrome (collectively referred to herein as CPPS) is a syndrome of undetermined etiology occurring in men. CPPS is the third of four subgroups of prostatitis recognized by the NIH. Category I encompasses acute bacterial prostatitis, and Category II covers chronic bacterial infection. Category III, CPPS, includes all remaining prostatitis syndromes, and is subdivided into IIIa (inflammatory) and IIIb (non-inflammatory). These sub-categories can be distinguished by the presence of leukocytosis in expressed prostatic secretions or sediment in a postmassage urine sample. Finally, Category IV represents asymptomatic prostatitis, which often is associated with benign prostate hyperplasia. Prostatitis is extraordinarily common, resulting in approximately 2 million office visits to primary care physicians and urologists in the United States annually [1997 American Urological Association Annual Meeting, National Ambulatory Medical Care Survey, National Center for Health Statistics, 1990 to 1994]. Patients with CPPS suffer from chronic, episodic pain in the perineum or pelvic region, irritative and obstructive voiding symptoms, and adverse effects upon sexual function [Alexander et al., Urology 48:568-574 (1996)]. Men with chronic prostatitis often require repeated physician visits, commonly to different physicians. Medical expenditures relating to CPPD are conservatively estimated to exceed half a billion dollars annually. Given its apparent prevalence, CPPS has defied characterization to an almost astonishing extent. While an enormous number of patients seek the care of a physician because of prostatitis-like symptoms, almost nothing is known about diagnostic criteria, etiology, or objective signs for CPPS. In a survey conducted through the Internet of 163 men with a diagnosis of prostatitis, Alexander and Trissel found that pain in the pelvic region was the most frequently reported and the most severe symptom in such patients [Alexander et al., Urology 48:568-74 (1996)]. It was because of these observations and the paucity of objective criteria for defining the disease, that the National Institute of Diabetes and Digestive and Kidney Diseases working group in prostatitis suggested that the disease be named Chronic Pelvic Pain Syndrome. Web site: http://www.delphion.com/details?pn=US06180355__ •

Method for treating chronic prostatitis or chronic pelvic pain syndrome Inventor(s): Nickel; Curtis J. (Elginburg, CA), Pontari; Michel A. (Lafayette Hill, PA), Stoner; Elizabeth (Westfield, NJ), Waldstreicher; Joanne (Scotch Plains, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ), Temple University of the Commonwealth of Higher Ed. (Philadelphia, PA) Patent Number: 6,403,640 Date filed: August 24, 2000 Abstract: The use of a COX-2 selective inhibitor for the treatment of chronic prostatitis or chronic pelvic pain syndrome is disclosed. Excerpt(s): Chronic prostatitis or chronic pelvic pain syndrome is an extremely prevalent disease in men (Collins M M, et al., "How common is prostatitis? A national survey of physician visits," Journal of Urology, 159:1224-1228 (1998)). Although the epidemiologic evidence is limited, it appears that the prevalence of prostatitis is approximately 2-9% in adult men. It has been suggested that 35-50% of men are affected by prostatitis at some time in life. Approximately 2 million ambulatory patient visits are

146 Interstitial Cystitis

made annually for prostatitis, accounting for 8% of all visits to urologists and 1% of all visits to primary care physicians. Many men remain symptomatic for much of their lives. Chronic prostatitis is characterized by evidence of prostatic inflammation and by the presence or absence of white blood cells in prostatic fluid and/or pain associated with the prostate. This syndrome does not exist prior to puberty but has a peak incidence between the ages of 18 and 50. Suggestions as to the origins of these conditions have included a chemical imbalance in the prostate, infection undetected by current microbiological methods and autoimmunity to the prostate gland itself. Chronic non-bacterial prostatitis and prostatodynia (Chronic Pelvic Pain Syndrome) is characterized by pain and/or discomfort in the genitourinary, pelvic or perineal area and is associated with variable voiding and sexual dysfunction. Chronic nonbacterial prostatitis [Chronic Pelvic Pain Syndrome NIH Category IIIA] is an inflammatory and painful condition of unknown etiology characterized by excessive inflammatory cells in prostatic secretions despite a lack of documented urinary tract infections, and negative bacterial cultures of urine and prostatic secretions. Prostatodynia [Chronic Pelvic Pain Syndrome NIH Category IIIB] is a painful condition of unknown etiology characterized by a decided lack of inflammatory cells in prostatic secretions, no documented urinary tract infections and negative bacterial cultures in urine and prostatic secretions. Chronic nonbacterial prostatitis is more common than bacterial prostatitis. Symptoms mimic those of chronic bacterial prostatitis. Patients usually show an increase in the number of white blood cells and oval fat bodies in their expressed prostatic secretions. However, they rarely have a history of urinary tract infection, and lower-tract localization cultures fail to reveal a pathogenic organism. Web site: http://www.delphion.com/details?pn=US06403640__ •

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,

Patents 147

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 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 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

148 Interstitial Cystitis

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__ •

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. 495500 (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__

Patents 149

•

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__

•

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

150 Interstitial Cystitis

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__ •

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 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

Patents 151

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__ •

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__

152 Interstitial Cystitis

Patent Applications on Interstitial Cystitis As of December 2000, U.S. patent applications are open to public viewing.7 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to interstitial 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. 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

7

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

Patents 153

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 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

154 Interstitial Cystitis

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 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

Patents 155

•

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

156 Interstitial Cystitis

•

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 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

Patents 157

•

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 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.

158 Interstitial Cystitis

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 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

Patents 159

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 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 •

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 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.

160 Interstitial Cystitis

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. 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

Patents 161

•

Treatment of male chronic pelvic pain syndrome Inventor(s): Cartt, Stephen LaHue; (San Carlos, CA) Correspondence: John A. Dhuey; Alza Corporation; P.O. Box 7210; Mountain View; CA; 94043-7210; US Patent Application Number: 20010034328 Date filed: February 16, 2001 Abstract: Dosage forms and methods for the treatment of symptoms of male chronic pelvic pain syndrome are described. Excerpt(s): This application claims the priority of U.S. application Ser. No. 60/185,185, filed Feb. 25, 2000, which is incorporated herein by reference. This invention pertains to the treatment of male chronic pelvic pain syndrome. In particular, the invention is directed to methods and dosage forms for the treatment of symptoms of male chronic pelvic pain syndrome, including, inter alia, pain, voiding dysfunction and sexual dysfunction, and for the treatment of underlying conditions, such as inflammatory or noninflammatory abacterial prostatitis. Parenthetical numerals in this section refer to the publications listed at the end of the section unless the context requires otherwise. 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

162 Interstitial Cystitis

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

Keeping Current In order to stay informed about patents and patent applications dealing with interstitial 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 “interstitial 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 interstitial cystitis. You can also use this procedure to view pending patent applications concerning interstitial 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.

163

CHAPTER 7. BOOKS ON INTERSTITIAL CYSTITIS Overview This chapter provides bibliographic book references relating to interstitial cystitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on interstitial 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 “interstitial 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 interstitial 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

164 Interstitial Cystitis

treatment process for IC. The primary object of the book is to build a framework for 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.

•

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

Books

165

important to emphasize that if symptoms have been present for more than a year, no 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 “interstitial cystitis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “interstitial cystitis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “interstitial 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

•

Along the Healing Path : Recovering from Interstitial Cystitis by Catherine M. Simone; ISBN: 0966775015; http://www.amazon.com/exec/obidos/ASIN/0966775015/icongroupinterna

•

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

•

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

•

Interstitial Cystitis by Grannum R. Sant (Editor) (1997); ISBN: 0397516959; http://www.amazon.com/exec/obidos/ASIN/0397516959/icongroupinterna

•

Interstitial Cystitis (1990); ISBN: 354019598X; http://www.amazon.com/exec/obidos/ASIN/354019598X/icongroupinterna

•

Interstitial Cystitis by Philip M. Hanno, David R. Staskin; ISBN: 038719598X; http://www.amazon.com/exec/obidos/ASIN/038719598X/icongroupinterna

•

Interstitial cystitis (SuDoc HE 20.3323/3:IN 8) by U.S. Dept of Health and Human Services; ISBN: B00010L9H2; http://www.amazon.com/exec/obidos/ASIN/B00010L9H2/icongroupinterna

•

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

166 Interstitial Cystitis

•

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

•

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

•

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

•

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

•

To Wake in Tears: Understanding Interstitial Cystitis by Catherine M. Simone (1998); ISBN: 0966775007; http://www.amazon.com/exec/obidos/ASIN/0966775007/icongroupinterna

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

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.

•

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.

Books

167

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. 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.

•

Painful Bladder Syndromes Source: in Hanno, P.M.; Malkowicz, S.B.; Wein, A.J. Clinical Manual of Urology. New York, NY: McGraw-Hill, Inc. 2001. p.199-212.

168 Interstitial Cystitis

Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $54.95;plus shipping and handling. ISBN: 0071362010. Summary: This 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 painful bladder syndromes, notably urethral syndrome and interstitial cystitis (IC). The painful bladder disease complex includes a large group of urologic patients with pain in the bladder, irritative voiding symptoms (urgency, frequency, nocturia or urinating at night, and dysuria, or painful urination), and sterile urine (no bacteria are present). The author notes that although the etiology (cause) of both urethral syndrome and IC remains in doubt, there is reason to believe that they may be varying manifestations of a single spectrum of disease. The author first reviews urethral syndrome, then focuses on the definition, epidemiology, etiology, and treatment of IC. A patient care algorithm is provided. The information in the chapter is presented in outline format, for ease of reference, and line drawings illustrate the chapter. The chapter concludes with a list of five self-assessment questions and their answers. 2 figures. 1 table. 8 references. •

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 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.

Books

•

169

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.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to interstitial cystitis have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:8 •

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

8 You will need to limit your search to “Directory” and “interstitial 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 “interstitial cystitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

170 Interstitial Cystitis

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.

171

CHAPTER 8. MULTIMEDIA ON INTERSTITIAL CYSTITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on interstitial 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 interstitial cystitis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “interstitial 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 “interstitial cystitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on interstitial cystitis: •

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

172 Interstitial Cystitis

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 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 Interstitial 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 interstitial 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 interstitial cystitis: •

Urethral syndrome and related urogynecological disorders [sound recording] Source: American College of Surgeons; Year: 1978; Format: Sound recording; [Chicago]: The College, [1978]

173

CHAPTER 9. PERIODICALS AND NEWS ON INTERSTITIAL CYSTITIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover interstitial cystitis.

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

Hormonal axis regulation linked to interstitial cystitis symptomatology Source: Reuters Medical News Date: March 29, 2002

174 Interstitial Cystitis

•

Interstitial cystitis is poorly understood syndrome Source: Reuters Medical News Date: January 05, 2001

•

Noninvasive urinary assay may prove useful for diagnosis of interstitial cystitis Source: Reuters Medical News Date: June 09, 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

•

Low-Dose Oral L-Arginine Decreases Interstitial Cystitis Symptoms Source: Reuters Medical News Date: December 01, 1997

•

Urine Epithelial Cell Growth Factor Levels Altered In Patients With Interstitial Cystitis Source: Reuters Medical News Date: October 16, 1997 The NIH

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

Periodicals and News

175

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 “interstitial 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 “interstitial cystitis” (or synonyms). If you know the name of a company that is relevant to interstitial 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 “interstitial 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 “interstitial 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 interstitial cystitis: •

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

176 Interstitial Cystitis

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.

Academic Periodicals covering Interstitial Cystitis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to interstitial cystitis. In addition to these sources, you can search for articles covering interstitial 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.”

177

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

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

178 Interstitial Cystitis

The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to interstitial cystitis: 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

Dimethyl Sulfoxide •

Mucosal - U.S. Brands: Rimso-50 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202196.html

Lidocaine •

Topical - U.S. Brands: Lidoderm http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500058.html

Pentosan •

Systemic - U.S. Brands: Elmiron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203359.html

Phenazopyridine •

Systemic - U.S. Brands: Azo-Standard; Baridium; Eridium; Geridium; Phenazodine; Pyridiate; Pyridium; Urodine; Urogesic; Viridium http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202455.html

Urea •

Intra-Amniotic - U.S. Brands: Ureaphil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202584.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

Researching Medications

179

adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

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 interstitial 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 “interstitial 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 interstitial 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

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

181

APPENDICES

183

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

9

These publications are typically written by one or more of the various NIH Institutes.

184 Interstitial Cystitis

•

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

Physician Resources

185

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.10 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:11 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 11 See http://www.nlm.nih.gov/databases/databases.html.

186 Interstitial Cystitis

•

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 “interstitial 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 “interstitial 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 Gateway12 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “interstitial 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.

12 13

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

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

Physician Resources

187

Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 1122 7 119 0 1 1249

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.16 Simply search by “interstitial cystitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists17 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.18 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.19 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

14

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

15

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

16

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 17 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 18 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 19 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

188 Interstitial Cystitis

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/.

189

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 interstitial 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 interstitial 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 interstitial 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 “interstitial cystitis”:

190 Interstitial Cystitis

•

Guides on interstitial cystitis Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html

•

Other guides Adrenal Gland Disorders http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Bladder Diseases http://www.nlm.nih.gov/medlineplus/bladderdiseases.html Candidiasis http://www.nlm.nih.gov/medlineplus/candidiasis.html Chiropractic http://www.nlm.nih.gov/medlineplus/chiropractic.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseases.html Endometriosis http://www.nlm.nih.gov/medlineplus/endometriosis.html Female Sexual Dysfunction http://www.nlm.nih.gov/medlineplus/femalesexualdysfunction.html Head and Neck Cancer http://www.nlm.nih.gov/medlineplus/headandneckcancer.html High Risk Pregnancy http://www.nlm.nih.gov/medlineplus/highriskpregnancy.html Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Irritable Bowel Syndrome http://www.nlm.nih.gov/medlineplus/irritablebowelsyndrome.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.html Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Oral Cancer http://www.nlm.nih.gov/medlineplus/oralcancer.html Prostate Diseases http://www.nlm.nih.gov/medlineplus/prostatediseases.html

Patient Resources

191

Secondhand Smoke http://www.nlm.nih.gov/medlineplus/secondhandsmoke.html Spinal Cord Injuries http://www.nlm.nih.gov/medlineplus/spinalcordinjuries.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html Urinary Tract Infections http://www.nlm.nih.gov/medlineplus/urinarytractinfections.html

Within the health topic page dedicated to interstitial cystitis, the following was listed: •

General/Overviews Most Frequently Asked Questions about IC Source: Interstitial Cystitis Association http://www.ichelp.org/WhatIsIC/TheMostFAQ.html

•

Diagnosis/Symptoms Cystoscopy http://www.nlm.nih.gov/medlineplus/tutorials/cystoscopyloader.html Diagnosis: Cystoscopy with Hydrodistention Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/CystoscopyAndHydrodistention. html IC and the Potassium Chloride Sensitivity Test Sensitivity Test Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/ICAndTheKClSensitivityTest.html Ultrasound-Pelvis Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/ultrasound-pelvis.htm

•

Treatment Bladder Retraining Program Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/BladderRetrainingProgram.html Interstitial Cystitis Study Finds Limited Benefit in Two Oral Drugs Source: National Institute of Diabetes and Digestive and Kidney Diseases http://www.nih.gov/news/pr/aug2003/niddk-13.htm Interstitial Cystitis: Treatment Options Source: Interstitial Cystitis Association http://WWW.IChelp.org/TreatmentAndSelfHelp/TreatmentGuidelines.html

192 Interstitial Cystitis

Oral Medications for IC: An Expanded Treatment Arsenal Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/OralMedsForIC.html Surgical Procedures Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/Surgery.html •

Alternative Therapy Treatment Options: All I Want Is a Remedy Source: Interstitial Cystitis Association http://WWW.IChelp.org/TreatmentAndSelfHelp/AllIWantIsARemedy.html

•

Nutrition IC and Diet Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/ICAndDiet.html

•

Coping Psychological Perspectives on Living with IC Source: Interstitial Cystitis Association http://www.ichelp.org/FeatureArticles/PsychologicalPerspectives.html

•

Specific Conditions/Aspects Finding the Right Physician for You Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/FindingTheRightPhysician.html IC and Other Diseases Source: Interstitial Cystitis Association http://www.ichelp.org/RelatedDiseases/ICAndOtherDiseases.html IC and Sexuality Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/SexAndIC.html

•

Children IC and Children Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/ICAndChildren.html

•

Law and Policy Disability Changes Benefit Working IC Patients Source: Interstitial Cystitis Association http://www.ichelp.org/Disability/DisabilityChangesBenefitWorkingICPatients.ht ml

Patient Resources

193

Eligibility for Social Security and SSI (Supplemental Security Income) Benefits Source: Interstitial Cystitis Association http://www.ichelp.org/Disability/EligibilityForSSAndSSIBenefits.html Long Awaited Social Security Disability Ruling Established for IC Source: Interstitial Cystitis Association http://www.ichelp.org/Disability/LongAwaitedSSDRulingForIC.html •

Men IC and Men Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/MenAndIC.html

•

Organizations Interstitial Cystitis Association http://www.ichelp.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/

•

Research Sacral Nerve Stimulation Can Relieve Interstitial Cystitis, Studies Suggest Source: Interstitial Cystitis Association http://WWW.IChelp.org/research/SacralNerveStimulationCanRelieveIC.html

•

Women IC and Pregnancy Source: Interstitial Cystitis Association http://www.ichelp.org/TreatmentAndSelfHelp/ICAndPregnancy.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on interstitial 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

194 Interstitial Cystitis

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 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.

Patient Resources

195

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.]. 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

196 Interstitial Cystitis

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.

•

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.].

Patient Resources

197

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. •

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

198 Interstitial Cystitis

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. 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.

•

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).

•

Interstitial Cystitis and InterStim Therapy Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2001. 2 p.

Patient Resources

199

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.

•

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

200 Interstitial Cystitis

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. •

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 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.

Patient Resources

201

The fact sheet briefly quotes related research studies, and includes the contact information for the Interstitial Cystitis Association (ICA). 3 references. (AA-M). •

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 catheterization. The fact sheet includes contact information for the Interstitial Cystitis Association (ICA). 3 references. (AA-M). Healthfinder™

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

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 interstitial 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.

202 Interstitial Cystitis

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

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

•

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

•

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

•

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

•

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

•

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

•

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

Associations and Interstitial Cystitis The following is a list of associations that provide information on and resources relating to interstitial 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. Relevant area(s) of interest: Interstitial Cystitis

Patient Resources

•

203

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 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. Relevant area(s) of interest: Interstitial Cystitis

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to interstitial cystitis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with interstitial 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 interstitial 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/.

204 Interstitial Cystitis

Simply type in “interstitial 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. 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 “interstitial 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 “interstitial 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 “interstitial cystitis” (or a synonym) into the search box, and click “Submit Query.”

205

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.20

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

20

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

206 Interstitial Cystitis

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)21: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

21

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

Finding Medical Libraries

207

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

208 Interstitial Cystitis

•

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

209

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

210 Interstitial Cystitis

•

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

211

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 interstitial cystitis: •

Basic Guidelines for Interstitial Cystitis Cystitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000521.htm Interstitial cystitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000477.htm Interstitial cystitis - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/005108.htm

•

Signs & Symptoms for Interstitial Cystitis Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm

212 Interstitial Cystitis

Dyspareunia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003157.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Pain during intercourse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003157.htm Sleeplessness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Urgent need to urinate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Urinary discomfort Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003145.htm Urinary frequency Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Urinary urgency Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm •

Diagnostics and Tests for Interstitial Cystitis ADH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003702.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Biopsy of the bladder Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003902.htm Cystoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003903.htm

•

Background Topics for Interstitial Cystitis Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm

Online Glossaries 213

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

215

INTERSTITIAL 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] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] 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] 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 renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] 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]

216 Interstitial Cystitis

Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine 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] 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]

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 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

Dictionary 217

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]

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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] 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] 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,

218 Interstitial Cystitis

magnet therapy, spiritual healing, and meditation. [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] 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] 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] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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]

Dictionary 219

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] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [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]

220 Interstitial Cystitis

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-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] 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

Dictionary 221

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] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] 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] Aspartate: A synthetic amino acid. [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] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] 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] 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] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls,

222 Interstitial Cystitis

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 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 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] 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]

Dictionary 223

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] 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] 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] Blepharitis: Inflammation of the eyelids. [NIH]

224 Interstitial Cystitis

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] 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] 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] 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] 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]

Dictionary 225

Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [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] 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] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [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] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] 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] Carboxy: Cannabinoid. [NIH]

226 Interstitial Cystitis

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 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] 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] 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 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 Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the

Dictionary 227

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 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 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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] 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] Checkup: A general physical examination. [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] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [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]

228 Interstitial Cystitis

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 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] 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 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] 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

Dictionary 229

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 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] Collagenous Colitis: A type of colitis. Caused by an abnormal band of collagen, a threadlike protein. [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] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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

230 Interstitial Cystitis

not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Concomitant: Accompanying; accessory; joined with another. [EU] 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 tissue cells embedded in a large amount of extracellular matrix. [NIH]

Dictionary 231

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] 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] 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] 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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to

232 Interstitial Cystitis

stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, 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] 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] Cystectomy: Used for excision of the urinary bladder. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystinuria: An inherited abnormality of renal tubular transport of dibasic amino acids leading to massive urinary excretion of cystine, lysine, arginine, and ornithine. [NIH]

Dictionary 233

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] 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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [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]

234 Interstitial Cystitis

Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] 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] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] 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]

Dictionary 235

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 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] 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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] 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]

236 Interstitial Cystitis

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] 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] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Painful sexual intercourse. [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] Ejaculation: The release of semen through the penis during orgasm. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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]

Dictionary 237

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]

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] 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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [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] 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 vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium,

238 Interstitial Cystitis

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] Enterocele: A hernia in the intestine. [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] 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] 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] 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

Dictionary 239

lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epidural block: An injection of an anesthetic drug into the space between the wall of the spinal canal and the covering of the spinal cord. [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] Epitopes: Sites on an antigen that interact with specific antibodies. [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]

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] 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] 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).

240 Interstitial Cystitis

[EU]

Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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] 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, 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] 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] 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]

Dictionary 241

Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fistulas: An abnormal passage from one hollow structure of the body to another, or from a hollow structure to the surface, formed by an abscess, disease process, incomplete closure of a wound, or by a congenital anomaly. [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] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] 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] 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

242 Interstitial Cystitis

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 in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] 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

Dictionary 243

in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic 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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

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] 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]

244 Interstitial Cystitis

Glycerophosphates: Any salt or ester of glycerophosphoric acid. [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] 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]

Dictionary 245

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] 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 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 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] 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.

246 Interstitial Cystitis

[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] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

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] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent.

Dictionary 247

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] 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] 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] 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 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] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [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]

248 Interstitial Cystitis

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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA 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] 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 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

Dictionary 249

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] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] 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]

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]

250 Interstitial Cystitis

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] 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 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] 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] Intracranial Hypertension: Increased pressure within the cranial vault. This may result

Dictionary 251

from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intravenous: IV. Into a vein. [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] 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] 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]

252 Interstitial Cystitis

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] 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] 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] 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 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] Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [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]

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]

Dictionary 253

Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [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 directly by white light. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] 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] 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] 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

254 Interstitial Cystitis

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] 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] 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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] 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] 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] 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] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [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 wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or

Dictionary 255

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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] 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] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] 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

256 Interstitial Cystitis

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 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] 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] 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

Dictionary 257

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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] 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

258 Interstitial Cystitis

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 carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] 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]

Dictionary 259

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] 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] 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] 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] 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] 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] 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

260 Interstitial Cystitis

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] 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]

Nitrocamptothecin: An alkaloid drug belonging to a class of anticancer agents called topoisomerase inhibitors. [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 transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are

Dictionary 261

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] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] 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

262 Interstitial Cystitis

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]

Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Opacity: Degree of density (area most dense taken for reading). [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] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] 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] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] 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]

Dictionary 263

Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] 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] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [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] Paralysis: Loss of ability to move all or part of the body. [NIH] 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] 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

264 Interstitial Cystitis

tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] 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]

Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perineal: Pertaining to the perineum. [EU]

Dictionary 265

Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Perivascular: Situated around a vessel. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] 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] 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 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]

266 Interstitial Cystitis

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] 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 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

Dictionary 267

mechanism leading to the formation of a thrombus. [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]

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [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] 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] 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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] 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]

268 Interstitial Cystitis

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] 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] Premenstrual: Occurring before menstruation. [EU] 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] 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] 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

Dictionary 269

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] 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 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]

270 Interstitial Cystitis

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 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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] 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]

Dictionary 271

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] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] 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] 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] 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

272 Interstitial Cystitis

more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] 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] 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

Dictionary 273

treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

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]

274 Interstitial Cystitis

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] Retrospective: Looking back at events that have already taken place. [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. 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] 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

Dictionary 275

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 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] 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]

276 Interstitial Cystitis

Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] 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]

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

Dictionary 277

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 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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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

278 Interstitial Cystitis

of the organism. [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 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] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem 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

Dictionary 279

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] 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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] 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]

280 Interstitial Cystitis

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 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] 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] 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]

Dictionary 281

Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire 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] 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] 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] 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] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] 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.

282 Interstitial Cystitis

(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] 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] 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] Topical: On the surface of the body. [NIH]

Dictionary 283

Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [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] 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] Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [NIH] Transitional cells: Cells that vary in shape depending on whether the tissue is being stretched. The cells may be stretched without breaking apart. They line hollow organs such as the bladder. [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]

284 Interstitial Cystitis

Tricyclic: Containing three fused rings or closed chains in the molecular structure. [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] 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; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] 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] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urethritis: Inflammation of the urethra. [EU] 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 Retention: Inability to urinate. The etiology of this disorder includes obstructive,

Dictionary 285

neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urinary urgency: Inability to delay urination. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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] 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] 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

286 Interstitial Cystitis

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] 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] 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] 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] 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] 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

Dictionary 287

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] Volition: Voluntary activity without external compulsion. [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]

289

INDEX 5 5-alpha, 161, 215, 241 A Abdomen, 167, 215, 224, 250, 253, 263, 265, 279, 281, 286 Abdominal, 5, 140, 149, 151, 154, 156, 159, 164, 215, 229, 251, 263, 265, 279, 284 Abdominal Cramps, 5, 215 Abdominal Pain, 140, 149, 215, 251, 284 Aberrant, 33, 69, 215 Abscess, 215, 241 Acceptor, 215, 244, 276 Acetylcholine, 215, 228, 260 Acetylglucosamine, 47, 215 Acne, 144, 215 Acoustic, 215, 250, 286 Actin, 66, 215 Activities of Daily Living, 22, 196, 215 Acute renal, 215, 245 Acute tubular, 34, 215 Adaptability, 215, 226, 227 Adaptation, 215, 266 Adenine, 215, 216 Adenoma, 99, 216 Adenosine, 78, 109, 155, 216, 265 Adenosine Triphosphate, 78, 109, 216, 265 Adhesions, 54, 216 Adjustment, 30, 215, 216 Adjuvant, 52, 158, 216, 242 Adjuvant Therapy, 52, 216 Adoptive Transfer, 31, 216 Adrenal Cortex, 216, 231, 239, 261, 268 Adrenal Medulla, 216, 226, 239, 260 Adrenergic, 56, 63, 98, 152, 153, 155, 216, 218, 235, 236, 239, 280 Adverse Effect, 11, 145, 216, 276 Aerobic, 140, 216, 256 Aeroembolism, 216, 222 Aerosol, 143, 216 Aetiology, 71, 93, 216 Afferent, 27, 28, 37, 40, 42, 56, 59, 61, 62, 67, 216 Affinity, 62, 65, 79, 216, 217, 253, 277 Agar, 217, 232 Agenesis, 217 Aggravation, 28, 217 Agonist, 27, 141, 159, 217, 235, 258 Airways, 142, 217

Albumin, 217, 262, 266 Algorithms, 11, 48, 217, 223 Alkaline, 217, 218, 225 Alkaloid, 217, 225, 257, 260 Alkylate, 34, 217 Alleles, 42, 217 Allergen, 217, 275 Aloe, 198, 217 Alopecia, 217, 232 Alpha Particles, 217, 271 Alpha-1, 217, 218 Alternative medicine, 174, 217 Amine, 218, 246 Amino Acid Sequence, 218, 219, 243 Amino Acids, 218, 232, 243, 259, 264, 267, 270, 274, 283, 284 Amitriptyline, 11, 51, 115, 176, 218 Ammonia, 218, 243, 284 Amplification, 75, 84, 103, 108, 218 Ampulla, 218, 237, 240 Anaerobic, 140, 156, 218 Anaesthesia, 218, 249 Anal, 218, 235, 238, 240, 241, 277 Anal Fissure, 218, 277 Analgesics, 63, 176, 218 Analogous, 20, 218, 267, 283 Anaphylactic, 218, 266 Anaphylatoxins, 218, 230 Anaphylaxis, 139, 153, 218 Anatomical, 9, 147, 156, 219, 224, 248, 275 Anemia, 219, 257 Anesthesia, 4, 8, 9, 25, 48, 96, 141, 153, 164, 194, 198, 218, 219, 232, 268 Anesthetics, 10, 219, 239 Angiogenesis, 72, 219, 254 Angiography, 90, 219 Animal model, 46, 55, 58, 67, 73, 219 Anionic, 46, 219 Annealing, 219, 267 Anomalies, 219, 257, 281 Antagonism, 219, 234, 236 Antibacterial, 142, 219, 278 Antibiotic, 15, 19, 139, 175, 198, 219, 233, 236, 278 Antibodies, 38, 61, 68, 79, 157, 219, 220, 221, 239, 245, 246, 254, 256, 257, 266 Antibody, 44, 68, 143, 217, 219, 220, 229, 245, 246, 248, 249, 254, 257, 271, 275, 278

290 Interstitial Cystitis

Anticholinergic, 218, 219, 227, 236 Anticoagulant, 219, 270 Antidepressant, 164, 218, 219 Antiemetic, 219, 247 Antifungal, 219, 252 Antigen-Antibody Complex, 220, 230 Antihypertensive, 220, 245 Anti-inflammatory, 33, 71, 139, 154, 220, 234, 243, 266 Anti-Inflammatory Agents, 154, 220 Antineoplastic, 220, 232, 236 Antioxidant, 220, 221 Antiproliferative, 17, 29, 70, 77, 80, 81, 102, 108, 126, 138, 152, 174, 220 Antiseptic, 220, 287 Antiserum, 66, 220 Antispasmodic, 156, 220 Antiviral, 220, 250, 264 Anus, 218, 220, 224, 265 Anxiety, 154, 155, 211, 220, 247 Aplasia, 169, 220 Apolipoproteins, 220, 253 Aponeurosis, 220, 242 Apoptosis, 44, 66, 220 Aqueous, 139, 220, 222, 233, 252 Arachidonic Acid, 46, 220, 236, 253, 269 Arginine, 7, 53, 56, 75, 86, 87, 104, 118, 123, 129, 160, 174, 218, 221, 232, 260, 262 Aromatic, 221, 281 Arrhythmia, 221, 286 Arterial, 221, 228, 247, 270, 281 Arteries, 221, 224, 231, 253, 255, 282 Arterioles, 221, 224 Ascites, 221, 261 Ascorbic Acid, 153, 221 Aspartate, 62, 221 Assay, 74, 174, 221, 248 Astringent, 221, 287 Asymptomatic, 145, 159, 221 Atopic, 45, 221 Attenuated, 221, 234 Autoantibodies, 23, 45, 78, 114, 149, 221 Autoantigens, 221 Autoimmune disease, 31, 149, 221, 258 Autoimmunity, 23, 146, 221 Autonomic, 58, 215, 221, 260, 265, 280 Autonomic Nervous System, 221, 265, 280 Axons, 38, 221, 259, 262, 268 B Bacillus, 30, 33, 45, 78, 106, 111, 139, 176, 221 Bacterial Infections, 53, 157, 222, 227

Bacterial toxin, 66, 222 Bactericidal, 142, 222 Bacteriophage, 222, 283 Bacterium, 65, 222, 245 Bacteriuria, 142, 222, 284 Basal Ganglia, 222, 242 Base, 29, 31, 38, 49, 52, 75, 77, 78, 104, 111, 120, 160, 215, 222, 225, 234, 243, 251, 281 Basement Membrane, 222, 226, 240 Basophil, 222, 246 Bends, 143, 222 Benign, 26, 57, 145, 147, 148, 156, 161, 169, 216, 222, 241, 242, 245, 259 Benign prostatic hyperplasia, 26, 147, 148, 161, 222, 241 Benzene, 222 Benzodiazepines, 155, 222 Beta-Thromboglobulin, 222, 250 Bile, 223, 242, 253, 279 Binding Sites, 46, 223 Biochemical, 41, 47, 49, 67, 141, 217, 223, 241, 252, 262, 276 Biological Markers, 23, 29, 61, 62, 223 Biological response modifier, 223, 250 Biological therapy, 223, 245 Biological Transport, 223, 234 Bioluminescence, 42, 223 Biomarkers, 71, 223 Biopsy, 4, 5, 9, 17, 21, 22, 29, 38, 48, 57, 79, 138, 141, 148, 164, 172, 212, 223, 264 Biopsy specimen, 22, 29, 38, 148, 223 Bioreactors, 42, 223 Biosynthesis, 46, 221, 223, 265 Biotechnology, 73, 174, 185, 223 Blepharitis, 139, 223 Blind spot, 5, 224 Bloating, 154, 224, 248, 251 Blood Coagulation, 224, 225, 282 Blood Platelets, 224, 267, 276, 282 Blood pressure, 215, 220, 224, 247, 257, 277 Blood vessel, 63, 142, 219, 224, 225, 226, 227, 237, 243, 245, 251, 255, 264, 271, 277, 279, 282, 285, 286 Body Fluids, 223, 224, 236, 277, 284 Body Regions, 224, 229 Bone Marrow, 222, 224, 248, 254, 257, 277, 279 Bowel, 9, 19, 80, 141, 156, 215, 218, 224, 234, 249, 250, 279, 284 Bowel Movement, 224, 234, 279 Bradykinin, 224, 260, 266

Index 291

Branch, 209, 224, 263, 271, 278, 280, 281, 282 Breakdown, 224, 234, 242 Bronchi, 224, 239 Bronchial, 142, 224, 246 Bronchitis, 144, 224, 228 Bronchoconstriction, 141, 224, 266 Bronchus, 224 Buccal, 143, 224, 254 Bupivacaine, 224, 253 Burns, 144, 224, 225 Burns, Electric, 224, 225 C Calcitonin Gene-Related Peptide, 45, 81, 225 Calcium, 11, 34, 80, 110, 118, 120, 147, 150, 155, 156, 198, 225, 230, 234, 254, 276, 286 Calcium Carbonate, 198, 225 Calcium channel blocker, 11, 147, 155, 225, 286 Calcium Channel Blockers, 11, 147, 155, 225 Calendula, 139, 225 Candidiasis, 190, 225 Candidosis, 225 Canonical, 62, 225 Capsaicin, 27, 28, 65, 133, 134, 225 Capsules, 225, 235, 242 Carbohydrate, 32, 225, 244, 267 Carboxy, 150, 225 Carcinogenesis, 147, 226, 265 Carcinogenic, 222, 226, 249, 269, 279 Carcinogens, 65, 147, 226, 258 Carcinoma, 10, 16, 31, 33, 57, 101, 148, 169, 226 Carcinoma in Situ, 10, 16, 57, 226 Cardiac, 144, 226, 236, 237, 239, 253, 258, 279 Cardiovascular, 226, 253, 276, 281 Carotenoids, 225, 226 Carrier Proteins, 226, 266 Case series, 226, 228 Catecholamine, 152, 153, 226, 235, 265 Catheterization, 201, 226, 251 Catheters, 33, 172, 226 Caudal, 226, 234, 247, 267 Causal, 226, 238 Cecum, 226, 252 Cell Adhesion, 42, 226 Cell Count, 22, 89, 91, 97, 105, 226 Cell Cycle, 72, 226 Cell Death, 66, 220, 226, 227, 258

Cell Division, 222, 226, 227, 245, 255, 256, 266, 269, 275, 277 Cell Lineage, 65, 226 Cell membrane, 223, 225, 226, 227, 239, 242, 265 Cell Physiology, 71, 227 Cell proliferation, 71, 138, 152, 159, 160, 227, 250, 276 Cell Respiration, 227, 256, 273 Cell Size, 227, 241 Cell Survival, 227, 245 Cell Transplantation, 227 Central Nervous System Infections, 227, 245 Cerebral, 27, 222, 227, 239, 241, 263, 278, 281 Cerebral Palsy, 227, 278 Cerebrovascular, 225, 227 Cerebrum, 227 Cetirizine, 227, 247 Checkup, 167, 227 Chemotactic Factors, 95, 113, 140, 227, 230 Chemotherapy, 216, 227 Chest Pain, 5, 227 Chiropractic, 190, 227 Cholesterol, 223, 227, 228, 253, 279 Cholesterol Esters, 228, 253 Cholinergic, 56, 63, 155, 218, 228 Chondroitin sulfate, 74, 111, 113, 118, 120, 228 Chromatin, 220, 228, 261, 278 Chromosomal, 218, 228 Chromosome, 54, 228, 253, 275 Chronic Disease, 10, 13, 112, 140, 157, 228 Chronic Obstructive Pulmonary Disease, 153, 228 Chronic prostatitis, 26, 32, 35, 36, 37, 39, 48, 51, 145, 161, 198, 228 Chronic renal, 149, 228, 267 Chylomicrons, 228, 253 Chymopapain, 228, 263 Cicatrix, 228, 251 Cimetidine, 17, 228 Citrus, 221, 228 Clear cell carcinoma, 228, 234 Clinical Protocols, 32, 49, 228 Clinical series, 8, 228 Clinical study, 228, 231 Cloning, 54, 223, 228 Cluster Analysis, 62, 229 Coagulation, 224, 229, 245, 252, 266, 282 Cochlear, 229, 282, 286

292 Interstitial Cystitis

Cochlear Diseases, 229, 282 Coenzyme, 221, 229 Cofactor, 229, 270, 282 Cohort Studies, 229, 238 Colic, 153, 229 Colitis, 191, 229, 251 Collagen, 222, 229, 240, 242, 251, 254, 266, 277 Collagenous Colitis, 85, 229 Collapse, 218, 224, 229 Colloidal, 217, 229, 237 Combination Therapy, 31, 229 Compassionate, 164, 165, 168, 197, 229 Complement, 34, 152, 218, 229, 230, 243, 254, 266, 275 Complementary and alternative medicine, 123, 129, 230 Complementary medicine, 123, 230 Complete remission, 230, 273 Computational Biology, 185, 230 Concomitant, 101, 230 Conduction, 143, 230, 281 Congestion, 5, 230, 239 Congestive heart failure, 153, 230 Conjugated, 47, 230, 233, 274 Conjunctiva, 230, 252 Conjunctivitis, 139, 230 Connective Tissue, 98, 148, 221, 224, 229, 230, 231, 240, 242, 244, 251, 255, 274, 281 Connective Tissue Cells, 230, 231 Consciousness, 218, 231, 235 Constipation, 156, 199, 231, 241, 245, 251 Constitutional, 231, 258 Constriction, 231, 251 Contracture, 84, 231 Contraindications, ii, 199, 231 Control group, 4, 5, 21, 231, 272 Controlled clinical trial, 36, 37, 38, 48, 51, 53, 231 Controlled study, 4, 75, 82, 231 Conventional therapy, 231 Conventional treatment, 171, 231 Cooperative group, 35, 231 Coordination, 53, 231, 257 Cornea, 231, 244, 252 Coronary, 150, 231, 255 Coronary Thrombosis, 231, 255 Corpus, 231, 264, 268, 281 Corpus Luteum, 231, 268 Cortex, 231, 239 Cortical, 34, 231 Cortisol, 86, 105, 217, 231

Cortisone, 232, 234 Cranial, 232, 245, 250, 262, 265, 286 Craniocerebral Trauma, 232, 245, 282 Creatine, 45, 232 Creatinine, 21, 232 Cromolyn Sodium, 138, 139, 232 Cross-Sectional Studies, 232, 238 Culture Media, 29, 217, 232 Cultured cells, 33, 42, 232 Curare, 232, 258 Curative, 13, 165, 232, 281 Cutaneous, 68, 225, 232, 251, 254, 263 Cyclic, 21, 56, 70, 114, 153, 232, 245, 260, 265, 269 Cyclophosphamide, 16, 37, 59, 232 Cystectomy, 17, 23, 63, 77, 89, 112, 158, 232 Cystine, 232 Cystinuria, 169, 232 Cystometrogram, 10, 21, 233 Cystoscopy, 4, 5, 9, 11, 12, 15, 18, 138, 140, 172, 176, 191, 194, 198, 212, 233 Cytochrome, 228, 233 Cytokine, 13, 33, 45, 56, 58, 67, 144, 233, 250 Cytoplasm, 220, 227, 233, 238, 244, 257, 274 Cytoprotection, 60, 233 Cytoskeleton, 42, 60, 233 Cytotoxic, 66, 225, 233, 248, 276 D Dairy Products, 196, 233 Data Collection, 38, 233 Databases, Bibliographic, 185, 233 Daunorubicin, 233, 236 Deamination, 233, 284 Decarboxylation, 233, 246 Decubitus, 143, 233 Decubitus Ulcer, 143, 233 Defense Mechanisms, 142, 234 Deletion, 220, 234 Delivery of Health Care, 197, 234 Denaturation, 234, 267 Dendrites, 234, 259 Density, 17, 22, 27, 234, 241, 253, 262, 278 Dermatitis, 45, 141, 144, 234, 236, 247 DES, 62, 218, 234 Dexamethasone, 87, 234 Diabetes Mellitus, 149, 234, 243 Diagnostic procedure, 137, 164, 175, 234 Diarrhea, 156, 234, 241, 251, 252 Diastolic, 234, 245, 247

Index 293

Diastolic blood pressure, 234, 245 Diencephalon, 234, 247, 281 Diffusion, 7, 223, 234, 249 Digestion, 43, 223, 224, 234, 248, 250, 253, 279, 285 Digestive system, 135, 234, 257 Dihydrotestosterone, 161, 215, 234, 272 Dilation, 141, 224, 234 Dilator, 155, 234 Diltiazem, 147, 234 Dilution, 172, 234 Dimethyl, 5, 9, 18, 20, 23, 85, 87, 90, 114, 139, 140, 164, 176, 178, 235 Direct, iii, 28, 41, 65, 71, 80, 142, 149, 157, 177, 235, 256, 272 Discriminant Analysis, 62, 235 Dissociation, 216, 235, 251 Distal, 56, 235, 236, 268, 270 Distention, 11, 25, 48, 52, 58, 70, 139, 140, 194, 198, 235 Diuretic, 235, 268 Diverticula, 9, 235 Diverticulum, 235 Dizziness, 5, 235 Domesticated, 235, 245 Dopamine, 154, 235 Dopamine Agonists, 154, 235 Dorsal, 235, 267, 278 Dorsum, 235, 242 Dosage Forms, 161, 235 Dose-dependent, 144, 235 Doxepin, 87, 236 Doxorubicin, 23, 236 Drive, ii, vi, 9, 12, 23, 45, 117, 148, 236 Drug Interactions, 178, 179, 236 Duct, 218, 226, 236, 239, 274 Duodenum, 223, 236, 237, 260, 279 Dysmenorrhea, 154, 236, 266 Dyspareunia, 5, 9, 12, 18, 24, 25, 155, 212, 236 Dystrophy, 23, 125, 236 Dysuria, 10, 20, 150, 151, 160, 168, 236 E Eczema, 139, 144, 236 Edema, 46, 148, 236, 251, 258, 261 Effector, 215, 229, 236, 260, 265 Efficacy, 7, 24, 49, 50, 51, 53, 63, 87, 104, 106, 107, 110, 111, 118, 120, 134, 158, 236, 283 Eicosanoids, 60, 236 Ejaculation, 236, 275 Electrode, 159, 236

Electrolyte, 236, 268, 277 Electron microscope, 149, 236 Electrons, 220, 222, 236, 251, 271 Electrophoresis, 62, 237 Embryo, 227, 237, 249, 261, 267 Emodin, 217, 237 Emollient, 237, 262 Emphysema, 228, 237 Empiric, 11, 24, 28, 46, 47, 138, 237 Empirical, 149, 167, 237 Encephalitis, 237 Encephalomyelitis, 149, 237 Endocarditis, 225, 237 Endocrine System, 237, 259 Endocrinology, 237, 245 Endocytosis, 40, 237 Endometrial, 237 Endometriosis, 16, 79, 190, 237 Endometrium, 237, 255 Endoscope, 237 Endoscopic, 8, 24, 57, 108, 196, 233, 237 Endoscopy, 57, 237 Endothelial cell, 34, 60, 72, 101, 237, 250, 282 Endothelium, 60, 72, 237, 238, 260 Endothelium, Lymphatic, 238 Endothelium, Vascular, 238 Endothelium-derived, 238, 260 Endotoxin, 238, 284 End-stage renal, 228, 238, 267 Enterocele, 77, 238 Environmental Exposure, 223, 238 Environmental Health, 184, 186, 238 Enzymatic, 56, 144, 225, 230, 238, 246, 263, 267 Enzyme Inhibitors, 238, 266 Eosinophil, 17, 92, 238 Eosinophilic, 16, 238 Epidemiologic Factors, 18, 238 Epidemiologic Studies, 19, 223, 238 Epidemiological, 4, 6, 22, 25, 58, 66, 238 Epidermal, 21, 70, 77, 79, 80, 108, 159, 160, 238, 251, 256 Epidermal Growth Factor, 21, 70, 77, 79, 80, 108, 159, 160, 238 Epidermis, 238, 251, 271 Epidural, 96, 239 Epidural block, 96, 239 Epinephrine, 216, 235, 239, 260, 284 Epithelial Cells, 24, 34, 42, 44, 67, 70, 79, 83, 84, 140, 146, 159, 238, 239

294 Interstitial Cystitis

Epithelium, 12, 23, 24, 33, 40, 42, 46, 55, 60, 64, 70, 138, 147, 159, 222, 237, 239 Epitopes, 67, 239 Erectile, 239, 264 Erythema, 239, 285 Erythrocytes, 219, 224, 239, 272, 275 Esophagus, 234, 239, 272, 279 Estradiol, 65, 239 Estrogen, 57, 64, 65, 155, 239 Estrogen receptor, 64, 65, 239 Eukaryotic Cells, 143, 239, 261, 262 Evacuation, 231, 239 Evoke, 239, 279 Excitability, 27, 67, 239, 258 Excitation, 239, 241 Exocrine, 141, 239, 263 Exocytosis, 40, 42, 239, 246 Exogenous, 30, 236, 239 Expectorant, 239, 268 Extensor, 240, 270 Extracellular, 42, 96, 230, 231, 237, 240, 254, 277 Extracellular Matrix, 230, 231, 240, 254 Extracellular Matrix Proteins, 240, 254 Extrapyramidal, 235, 240 Extravasation, 46, 66, 240 F Fallopian Tubes, 240, 273, 284 Family Planning, 185, 240 Fat, 146, 220, 224, 233, 240, 253, 258, 274 Fatigue, 22, 240, 245 Fatty acids, 217, 236, 240, 269, 282 Fecal Incontinence, 159, 240, 248 Feces, 54, 231, 240, 279 Fertilizers, 240, 260, 268 Fibrinogen, 240, 266, 281 Fibroblasts, 72, 231, 240, 250, 277 Fibrosis, 34, 72, 148, 169, 231, 240, 275 Finasteride, 161, 241 Fistulas, 143, 241 Fixation, 241, 275 Flatus, 240, 241, 242 Flow Cytometry, 71, 241 Fluorescence, 42, 241 Fluorescent Dyes, 241 Foetoplacental, 241, 261 Follicular Phase, 59, 241 Fourth Ventricle, 241, 253, 281 Functional Disorders, 73, 241 Fungi, 219, 223, 242, 256, 287 Fungicide, 34, 242 Fungus, 225, 242

G Gallbladder, 215, 234, 242 Ganglia, 37, 215, 242, 259, 265, 280 Ganglion, 38, 242, 262, 286 Gap Junctions, 242, 280 Gas, 216, 218, 222, 234, 241, 242, 247, 248, 251, 258, 260 Gastric, 141, 228, 235, 238, 242, 246, 247, 264 Gastric Acid, 141, 228, 242 Gastrin, 228, 242, 246 Gastritis, 4, 242 Gastrointestinal, 55, 58, 139, 142, 197, 224, 239, 242, 252, 253, 264, 266, 276, 280, 281, 284 Gastrointestinal tract, 142, 242, 252, 253, 264, 276, 284 Gelatin, 232, 242, 281 Gene, 13, 31, 34, 43, 63, 65, 69, 72, 81, 217, 223, 225, 242, 243, 266, 275 Gene Expression, 13, 43, 63, 69, 72, 81, 242 Generator, 62, 242 Genetic Code, 243, 261 Genetic Engineering, 223, 228, 243 Genetic testing, 243, 267 Genetics, 53, 243 Genital, 156, 228, 243, 245, 285, 287 Genitourinary, 37, 142, 146, 157, 243, 281, 285 Genotype, 243, 265 Gland, 190, 216, 232, 243, 263, 269, 275, 279, 280 Glomerular, 72, 243, 273 Glomeruli, 243, 271 Glomerulus, 243 Glucocorticoid, 234, 243 Glucose, 221, 234, 243, 244, 249, 274, 285 Glucose Intolerance, 234, 243 Glucuronic Acid, 243, 246 Glutamate, 62, 243 Glutamic Acid, 243 Glutamine, 66, 243 Glycerophosphates, 156, 244 Glycolysis, 156, 244 Glycoprotein, 17, 29, 70, 84, 113, 240, 244, 252, 276, 282, 284 Glycosaminoglycan, 23, 28, 43, 110, 113, 147, 228, 244 Glycosuria, 169, 244 Glycosyltransferases, 33, 244 Goats, 233, 244 Gonad, 244

Index 295

Gonadal, 58, 244, 279 Gonorrhea, 143, 244 Governing Board, 244, 268 Gp120, 244, 264 Grade, 147, 244 Graft, 244, 246, 248 Graft Rejection, 244, 248 Grafting, 63, 244, 248 Granulation Tissue, 22, 244 Granulocytes, 222, 244, 252, 276, 287 Gravis, 149, 153, 244 Growth, 21, 63, 66, 70, 72, 76, 77, 79, 82, 101, 108, 142, 143, 147, 159, 160, 174, 219, 220, 226, 227, 232, 238, 240, 244, 245, 250, 254, 259, 262, 265, 266, 273, 275, 277, 280, 283, 284 Growth factors, 63, 70, 72, 82, 245, 250 Guanfacine, 27, 245 Guanylate Cyclase, 245, 260 Guinea Pigs, 60, 245 Gynecology, 52, 85, 90, 93, 101, 126, 245 H Half-Life, 245, 266 Haptens, 216, 245 Headache, 5, 154, 245 Headache Disorders, 245 Health Services, 30, 234, 245 Heart failure, 245, 261 Hematuria, 7, 108, 169, 245 Hemodialysis, 225, 245 Hemolytic, 169, 245 Hemorrhage, 22, 153, 232, 245, 271, 279 Hemorrhoids, 144, 245, 277 Hemostasis, 245, 276 Heparin, 7, 11, 18, 21, 23, 25, 29, 46, 53, 55, 70, 77, 79, 80, 87, 108, 114, 139, 143, 144, 159, 160, 196, 198, 201, 246, 267 Hepatic, 169, 217, 246 Heredity, 242, 243, 246 Hernia, 238, 246 Heterogeneity, 217, 246 Hexosyltransferases, 244, 246 Histamine, 66, 85, 90, 91, 120, 134, 139, 141, 148, 218, 227, 228, 236, 246, 247 Histamine Release, 85, 141, 218, 246 Histidine, 246 Histology, 9, 89, 246 Homogeneous, 15, 246, 265 Homologous, 217, 246, 250, 275, 280 Hormonal, 58, 59, 153, 173, 175, 203, 246

Hormone, 64, 65, 83, 216, 223, 231, 232, 234, 236, 239, 242, 246, 249, 263, 268, 274, 276, 281 Hormone therapy, 216, 246 Host, 32, 54, 63, 222, 225, 246, 248, 253, 286 Hybrid, 246 Hybridization, 34, 246 Hybridomas, 246, 250 Hydrochloric Acid, 246, 263 Hydrogen, 215, 218, 222, 225, 234, 240, 247, 256, 257, 260, 261, 270 Hydrolysis, 244, 247, 267, 270 Hydrophilic, 147, 247 Hydrophobic, 247, 253 Hydroxyzine, 7, 75, 91, 176, 247 Hyperaemia, 230, 247 Hyperalgesia, 46, 64, 68, 247 Hyperplasia, 145, 247 Hypersensitivity, 15, 40, 46, 62, 79, 217, 218, 238, 247, 253, 274, 275 Hypertension, 150, 153, 225, 247, 251 Hypertrophy, 156, 222, 247 Hypotension, 153, 247, 259, 266 Hypothalamic, 65, 247 Hypothalamus, 65, 221, 234, 247, 259, 281 Hypoxia, 72, 247 Hysterectomy, 16, 22, 247 I Id, 121, 128, 202, 208, 210, 247 Idiopathic, 15, 18, 86, 95, 148, 247 Ileal, 186, 247 Ileum, 226, 247, 259 Immune function, 175, 247, 248 Immune response, 107, 158, 216, 220, 221, 232, 244, 245, 247, 248, 254, 275, 280, 286 Immune system, 45, 49, 149, 221, 223, 247, 248, 253, 254, 258, 285, 287 Immunity, 31, 44, 248 Immunization, 216, 248, 275 Immunoassay, 72, 248 Immunofluorescence, 248, 256 Immunogenic, 149, 248 Immunoglobulin, 143, 219, 248, 257 Immunologic, 31, 58, 73, 91, 216, 227, 248 Immunology, 54, 73, 91, 101, 107, 115, 216, 241, 248 Immunosuppressive, 11, 149, 232, 243, 248 Immunosuppressive Agents, 11, 248 Immunosuppressive therapy, 248 Immunotherapy, 78, 158, 216, 223, 248 Impairment, 73, 248, 255 Implantation, 7, 9, 33, 248, 261

296 Interstitial Cystitis

In situ, 54, 60, 72, 248 In vitro, 27, 34, 38, 42, 44, 56, 63, 70, 71, 74, 84, 142, 143, 144, 248, 267, 282 In vivo, 34, 37, 40, 44, 54, 57, 63, 64, 65, 71, 144, 246, 248, 282 Incision, 248, 251 Incontinence, 59, 124, 128, 151, 159, 164, 165, 167, 168, 199, 212, 248 Indicative, 165, 248, 263, 285 Indigestion, 248, 252 Induction, 31, 46, 56, 59, 249 Infarction, 222, 231, 249, 255 Infertility, 155, 249, 285 Infiltration, 15, 97, 105, 249, 268 Inflammatory bowel disease, 156, 249 Inhalation, 216, 249, 267 Initiation, 44, 51, 56, 151, 249 Innervation, 63, 148, 236, 249, 275, 282 Inorganic, 244, 249, 254, 257, 260 Inotropic, 235, 249 Insight, 29, 43, 53, 249 Insomnia, 154, 249 Instillation, 5, 12, 20, 25, 31, 34, 48, 81, 133, 164, 176, 201, 249 Insulator, 249, 258 Insulin, 21, 70, 149, 249, 250, 277 Insulin-dependent diabetes mellitus, 249 Insulin-like, 21, 70, 250, 277 Insulin-Like Growth Factor Binding Protein 3, 70, 250 Interferometry, 57, 250 Interferon, 51, 250 Interferon-alpha, 51, 250 Interleukin-2, 45, 250 Interleukin-4, 98, 250 Interleukin-6, 45, 66, 70, 250 Interleukin-8, 70, 250 Interleukins, 248, 250 Intermittent, 5, 9, 250 Internal Medicine, 36, 237, 250 Intestinal, 141, 156, 250 Intestine, 97, 105, 224, 238, 250, 252 Intoxication, 250, 287 Intracellular, 38, 42, 67, 69, 120, 225, 249, 250, 260, 268, 269, 272, 276 Intracranial Hypertension, 245, 250, 282 Intravenous, 144, 251 Intrinsic, 65, 139, 142, 217, 222, 251 Intubation, 226, 251 Invasive, 9, 138, 141, 155, 158, 176, 199, 203, 248, 251

Involuntary, 155, 240, 251, 258, 272, 277, 278, 279, 282 Ion Channels, 27, 28, 251, 260, 280 Ionization, 62, 251 Ions, 222, 235, 236, 247, 251, 256 Irrigation, 142, 251 Irritable Bowel Syndrome, 56, 73, 97, 153, 156, 190, 199, 200, 241, 251 Irritants, 65, 147, 251 Ischemia, 60, 72, 233, 251 J Joint, 53, 216, 251, 262, 280, 281 K Kb, 54, 184, 251 Keloid, 143, 251 Keratinocytes, 250, 251 Keratitis, 139, 252 Keratoconjunctivitis, 139, 252 Ketoconazole, 139, 252 Kidney Pelvis, 252, 284 Kinetic, 65, 252 L Labile, 229, 252 Labyrinth, 252, 286 Lactation, 252, 262, 263 Lactose Intolerance, 156, 252 Large Intestine, 156, 226, 234, 250, 252, 272, 277 Laser Surgery, 200, 252 Latent, 30, 252 Lavage, 23, 252 Lectins, 46, 252 Leisure Activities, 22, 252 Lens, 252, 273 Lesion, 252, 253, 276, 284 Lethal, 222, 252, 258 Lethargy, 154, 252 Leucocyte, 217, 238, 252 Leukemia, 236, 252 Leukocytes, 46, 60, 66, 224, 227, 244, 250, 252, 253, 257, 284 Leukocytosis, 145, 253 Leukotrienes, 221, 236, 253 Library Services, 208, 253 Lidocaine, 10, 76, 87, 178, 253 Ligament, 253, 269 Ligands, 46, 142, 253 Ligation, 253 Light microscope, 149, 253 Linkage, 42, 253 Lipid, 220, 249, 253, 258 Lipophilic, 56, 253

Index 297

Lipopolysaccharide, 64, 253 Lipoprotein, 144, 253 Liver, 34, 170, 215, 217, 221, 223, 232, 234, 240, 242, 243, 246, 253, 277, 281, 284 Localization, 34, 56, 64, 146, 253 Localized, 139, 151, 215, 241, 249, 253, 261, 266, 275, 284, 285 Locus Coeruleus, 27, 253 Low-density lipoprotein, 253 Luciferase, 42, 253 Lumbar, 96, 254, 275, 282 Lumen, 142, 147, 238, 254 Lupus, 254, 281 Lymph, 237, 238, 254, 280 Lymphatic, 238, 249, 254, 255, 261, 277 Lymphocyte, 96, 220, 254 Lymphoid, 219, 244, 252, 254 Lysine, 232, 254 M Magnesium Hydroxide, 198, 254 Major Histocompatibility Complex, 250, 254 Malformation, 254, 273 Malignancy, 33, 57, 158, 254 Malignant, 158, 220, 226, 254, 257, 259 Malignant tumor, 158, 226, 254, 257 Mastocytosis, 65, 254 Matrix metalloproteinase, 43, 254 Medial, 254, 262, 282 Mediate, 56, 235, 254 Mediator, 46, 56, 64, 66, 68, 250, 254, 267, 276 Medical Records, 12, 254 MEDLINE, 5, 17, 185, 255 Medullary, 169, 255 Meiosis, 255, 280 Melanin, 253, 255, 284 Meninges, 227, 232, 255 Menopause, 255, 262, 267 Menstrual Cycle, 59, 64, 113, 153, 241, 255, 261, 268 Menstruation, 236, 241, 255, 268 Mental Disorders, 135, 255 Mental Health, iv, 14, 26, 108, 135, 184, 187, 255, 271 Menthol, 160, 255 Mercury, 241, 255 Mesencephalic, 253, 255 Mesenchymal, 238, 255 Meta-Analysis, 87, 255 Metabolite, 35, 235, 247, 255 Metastasis, 57, 254, 255, 259

Methionine, 235, 255 MI, 86, 152, 213, 255 Microbe, 255, 283 Microbiological, 146, 256 Microbiology, 53, 54, 66, 73, 215, 222, 256 Microorganism, 229, 256, 263, 286 Microscopy, 53, 57, 222, 256, 261 Microscopy, Polarization, 57, 256 Micturition, 37, 55, 63, 151, 154, 256 Migration, 63, 72, 140, 256 Milliliter, 143, 144, 256 Mitochondria, 34, 256, 262 Mitochondrial Swelling, 256, 258 Mitosis, 220, 252, 256 Mixed Connective Tissue Disease, 149, 256 Modeling, 30, 256 Modification, 10, 19, 20, 23, 52, 72, 167, 169, 172, 243, 256, 271 Modulator, 49, 256 Molecular mass, 43, 110, 256 Molecular Structure, 256, 284 Monitor, 17, 55, 232, 257, 260 Monoclonal, 33, 67, 246, 257, 271 Monoclonal antibodies, 33, 67, 257 Monocytes, 250, 252, 257, 266 Mononuclear, 17, 257, 284 Monophosphate, 21, 257 Morphine, 257, 258 Morphological, 28, 41, 57, 150, 237, 242, 257 Morphology, 34, 57, 63, 149, 257 Motility, 156, 242, 257, 276 Motion Sickness, 257, 258 Motor nerve, 257, 258 Mucinous, 242, 257 Mucosa, 22, 34, 54, 134, 140, 142, 254, 257 Mucosal Lining, 31, 257 Mucositis, 257, 282 Mucus, 239, 257, 284 Multicenter Studies, 48, 257 Multicenter study, 257 Multiple Myeloma, 169, 257 Multiple sclerosis, 141, 149, 257 Muscle relaxant, 139, 176, 258 Muscle tension, 258 Muscular Dystrophies, 236, 258 Musculature, 52, 60, 258 Mustard Gas, 251, 258 Myasthenia, 149, 258 Mydriatic, 234, 258 Myelin, 258

298 Interstitial Cystitis

Myocardium, 143, 255, 258 Myopathy, 84, 258 N Naloxone, 258 Naltrexone, 148, 258 Narcosis, 258 Narcotic, 148, 257, 258 Narcotic Antagonists, 148, 258 Nausea, 5, 219, 235, 248, 258, 284 NCI, 1, 134, 183, 258 Necrosis, 34, 116, 220, 249, 255, 258 Neodymium, 115, 259 Neonatal, 40, 259 Neoplasia, 18, 259 Neoplasms, 216, 220, 226, 233, 259 Nephropathy, 73, 169, 252, 259 Nephrotoxic, 35, 259 Nerve Endings, 259, 260 Nerve Fibers, 63, 65, 97, 134, 259, 282 Nerve Growth Factor, 37, 61, 64, 88, 106, 147, 259 Nervous System, 27, 59, 73, 215, 216, 221, 222, 227, 242, 243, 245, 253, 254, 257, 258, 259, 260, 262, 265, 270, 276, 280, 281 Networks, 34, 62, 259 Neural, 27, 62, 67, 142, 151, 216, 225, 259 Neuroendocrine, 69, 73, 259 Neurogenic, 39, 46, 56, 67, 118, 142, 259, 285 Neuromuscular, 215, 259, 281 Neuronal, 28, 40, 55, 63, 258, 259 Neurons, 27, 28, 38, 42, 56, 67, 234, 242, 258, 259, 260, 280, 286 Neuropeptide, 225, 259 Neurotensin, 65, 259 Neurotransmitters, 218, 236, 257, 259, 260, 268 Neutrons, 217, 260, 271 Neutropenia, 260, 266 Neutrophil, 56, 113, 140, 260 Nitrates, 21, 260 Nitric acid, 260 Nitric Oxide, 56, 61, 67, 70, 86, 87, 114, 118, 157, 260 Nitrocamptothecin, 123, 260 Nitrogen, 217, 218, 232, 240, 241, 243, 256, 260, 284 Nociceptors, 27, 260 Nocturia, 7, 8, 12, 16, 17, 21, 33, 55, 150, 160, 168, 260 Nonmalignant, 7, 11, 260 Norepinephrine, 27, 88, 216, 218, 235, 260

Nuclear, 33, 61, 66, 69, 103, 222, 236, 239, 242, 256, 258, 260, 261 Nuclear Matrix, 61, 260 Nuclear Pore, 261 Nucleic acid, 158, 243, 246, 260, 261 Nucleic Acid Hybridization, 246, 261 Nucleolus, 261, 274 Nucleus, 61, 69, 220, 221, 228, 232, 233, 239, 253, 255, 257, 260, 261, 269, 270, 279, 286 Nurse Practitioners, 92, 93, 261 Nursing Care, 261, 264 Nursing Staff, 10, 261 O Observational study, 30, 261 Odds Ratio, 261, 273 Oedema, 141, 261 Oestrogen, 79, 100, 261 Office Visits, 145, 262 Ointments, 139, 235, 262, 287 Opacity, 234, 262 Optic Chiasm, 247, 262 Optic Nerve, 224, 262, 274 Organ Culture, 262, 282 Organelles, 54, 233, 257, 262, 266 Ornithine, 232, 262 Osteoarthritis, 262, 266 Osteoporosis, 262 Outpatient, 32, 262 Ovalbumin, 31, 44, 60, 262 Ovaries, 240, 262, 273, 276, 281, 284 Ovary, 231, 239, 244, 261, 262, 263, 267 Overactive bladder, 153, 160, 262 Ovulation, 241, 262, 263 Ovum, 231, 263, 268 Oxygen Consumption, 34, 263, 273 Oxygenation, 72, 263 Oxytocin, 58, 73, 263 P Pain Measurement, 38, 263 Painful bladder syndrome, 28, 61, 164, 168, 263 Palliative, 13, 52, 262, 263, 281 Pancreas, 215, 223, 234, 249, 263, 284 Pancreatic, 123, 263 Pancreatic cancer, 123, 263 Papain, 154, 263 Paralysis, 232, 255, 263, 278, 281 Paresthesia, 263, 281 Parietal, 141, 263, 267 Parietal Cells, 141, 263 Parietal Lobe, 263

Index 299

Partial remission, 138, 160, 263, 273 Partial response, 263 Particle, 263, 278, 283 Partnership Practice, 263, 268 Patella, 169, 263 Pathogen, 54, 263 Pathologic, 12, 24, 56, 70, 164, 220, 223, 225, 231, 247, 263, 270 Pathologic Processes, 220, 263 Pathologies, 33, 101, 119, 264 Pathophysiology, 5, 7, 9, 17, 37, 43, 46, 49, 61, 66, 67, 93, 101, 264 Patient Advocacy, 43, 194, 202, 264 Patient Care Management, 19, 264 Patient Education, 17, 25, 171, 172, 193, 206, 208, 213, 264 Pelvic inflammatory disease, 194, 264 Penis, 25, 236, 264, 273 Pentosan polysulfate, 9, 18, 43, 46, 55, 75, 87, 96, 104, 139, 161, 164, 176, 264 Pentosyltransferases, 244, 264 Pepsin, 228, 264 Pepsin A, 228, 264 Peptide, 38, 70, 150, 225, 264, 267, 270 Peptide T, 70, 264 Perception, 26, 156, 264, 274 Percutaneous, 7, 102, 106, 126, 264 Perforation, 80, 264 Perfusion, 223, 247, 264 Pericardium, 264, 281 Perineal, 11, 29, 146, 150, 164, 264 Perineum, 25, 145, 264, 265 Peripheral blood, 250, 265 Peripheral Nervous System, 151, 265, 268, 280 Peritoneal, 221, 261, 265 Peritoneal Cavity, 221, 261, 265 Perivascular, 141, 225, 265 Phagocytosis, 56, 265 Pharmaceutical Solutions, 235, 265 Pharmacologic, 27, 28, 67, 219, 245, 265, 283, 285 Pharmacotherapy, 10, 23, 265 Phenotype, 24, 40, 223, 265 Phosphodiesterase, 155, 265 Phosphodiesterase Inhibitors, 155, 265 Phospholipids, 240, 253, 265 Phosphorus, 225, 265 Phosphorylation, 46, 265 Phosphotyrosine, 140, 265 Physical Examination, 12, 77, 164, 227, 265 Physical Therapy, 10, 25, 110, 266

Physician Assistants, 12, 266 Physiologic, 18, 56, 63, 86, 217, 223, 245, 255, 266, 269, 272 Physiology, 16, 33, 72, 164, 215, 223, 237, 245, 252, 266 Pilot study, 49, 53, 98, 102, 266 Piroxicam, 87, 266 Placenta, 239, 241, 266, 268 Plants, 217, 228, 237, 243, 257, 260, 266, 267, 274, 283, 284 Plasma cells, 219, 244, 257, 266 Plasma protein, 62, 217, 238, 266 Plasticity, 37, 266 Plastids, 262, 266 Platelet Activating Factor, 60, 266 Platelet Aggregation, 218, 260, 266, 267, 282 Platelet Factor 4, 250, 267 Platelets, 222, 260, 266, 267, 282 Pleural, 261, 267 Pleural cavity, 261, 267 Poisoning, 250, 255, 258, 267 Pollen, 94, 227, 267, 271 Polycystic, 157, 169, 267 Polycystic Kidney Diseases, 169, 267 Polymerase, 103, 108, 267 Polymerase Chain Reaction, 108, 267 Polypeptide, 38, 218, 229, 238, 240, 246, 264, 267, 287 Polysaccharide, 47, 99, 220, 244, 267, 270 Posterior, 127, 218, 235, 263, 267 Postmenopausal, 11, 103, 262, 267 Postnatal, 267, 279 Postoperative, 266, 267 Postsynaptic, 268, 276, 280 Potassium Chloride, 25, 191, 195, 268 Potassium Citrate, 172, 268 Potentiating, 218, 268 Practicability, 268, 283 Practice Guidelines, 187, 268 Precursor, 221, 232, 235, 236, 238, 260, 268, 284 Premenstrual, 19, 153, 268 Presumptive, 10, 18, 268 Presynaptic, 236, 259, 268, 280 Presynaptic Terminals, 236, 259, 268 Prevalence, 6, 8, 12, 41, 48, 103, 120, 145, 261, 268 Private Practice, 47, 268 Procaine, 253, 268 Progesterone, 154, 268, 279

300 Interstitial Cystitis

Progression, 39, 48, 72, 147, 149, 158, 164, 219, 268 Progressive, 37, 148, 228, 244, 258, 262, 267, 268, 273, 284 Projection, 234, 260, 262, 269 Promoter, 31, 34, 269 Prone, 57, 269 Prophase, 269, 280 Prophylaxis, 149, 269 Proportional, 143, 263, 269 Prospective study, 75, 104, 107, 115, 269 Prostaglandin, 56, 81, 118, 134, 269, 282 Prostaglandins A, 269 Prostate gland, 146, 161, 228, 269 Prostatic Hyperplasia, 161, 269 Prostatitis, 11, 13, 20, 35, 36, 37, 41, 48, 49, 50, 52, 66, 100, 129, 145, 151, 161, 169, 270 Protease, 60, 154, 229, 270 Protective Agents, 225, 270 Protein C, 61, 217, 218, 220, 222, 253, 270, 284 Protein Kinases, 42, 270 Protein S, 223, 243, 270, 274 Proteinuria, 257, 270 Proteoglycans, 72, 74, 118, 140, 222, 240, 270 Proteolytic, 154, 217, 230, 240, 263, 270 Protocol, 19, 38, 48, 50, 51, 52, 172, 270 Protons, 217, 247, 270, 271 Protozoa, 223, 256, 270 Proximal, 34, 64, 235, 268, 270 Pruritic, 236, 270 Pruritus, 247, 270 Pseudorabies, 65, 270 Psoriasis, 139, 143, 258, 270 Psychiatric, 223, 255, 270, 277 Psychic, 270, 271 Psychogenic, 271, 285 Psychosomatic, 198, 271 Puberty, 146, 271 Public Health, 41, 187, 271 Public Policy, 185, 271 Pulmonary, 143, 224, 238, 253, 271 Pulse, 257, 271 Pupil, 231, 234, 258, 271 Purpura, 169, 271 Purulent, 271, 285 Pyelonephritis, 54, 66, 186, 271 Q Quality of Life, 7, 12, 14, 15, 29, 35, 38, 41, 48, 52, 73, 84, 148, 162, 271

Quercetin, 112, 120, 128, 154, 198, 271 R Race, 50, 256, 271 Radiation, 16, 59, 216, 238, 241, 264, 271, 287 Radiation therapy, 216, 264, 271 Radical cystectomy, 158, 271 Radioactive, 245, 247, 248, 251, 257, 260, 271, 272 Radiological, 191, 264, 271 Radiopharmaceutical, 243, 271 Random Allocation, 272 Randomization, 38, 272 Randomized, 31, 35, 36, 37, 38, 47, 48, 51, 52, 53, 75, 104, 118, 133, 236, 272 Randomized clinical trial, 35, 104, 272 Reagent, 157, 246, 254, 272 Receptors, Serotonin, 272, 276 Recombinant, 106, 160, 223, 272, 286 Reconstitution, 65, 272 Rectum, 220, 224, 234, 241, 242, 248, 249, 252, 269, 272 Recurrence, 158, 272 Red blood cells, 239, 245, 272, 274 Reductase, 155, 161, 241, 272 Refer, 1, 161, 224, 229, 235, 241, 242, 253, 260, 272, 286 Reflex, 23, 28, 37, 39, 125, 272 Reflux, 157, 272 Refraction, 272, 278 Refractory, 7, 16, 78, 100, 107, 113, 186, 272 Regeneration, 63, 272 Regimen, 6, 228, 236, 265, 272 Regression Analysis, 235, 273 Relapse, 165, 273 Relative risk, 42, 273 Relaxant, 273 Remission, 6, 9, 12, 165, 171, 272, 273 Renal agenesis, 169, 273 Renal failure, 72, 273 Renal pelvis, 64, 273, 283 Renal tubular, 232, 273 Reproductive system, 269, 273 Research Design, 37, 273 Resection, 9, 82, 124, 158, 273 Resolving, 70, 273 Respiration, 232, 257, 273 Response rate, 8, 31, 45, 273 Restoration, 266, 272, 273, 287 Retina, 224, 252, 262, 274 Retrospective, 20, 21, 274 Rheumatism, 274

Index 301

Rheumatoid, 68, 149, 157, 266, 274 Rheumatoid arthritis, 68, 149, 157, 266, 274 Ribonuclease, 256, 274 Ribonucleoproteins, 261, 274 Ribose, 216, 274, 282 Ribosome, 274, 283 Risk factor, 18, 22, 28, 41, 169, 238, 269, 273, 274 Rod, 221, 222, 274 Rutin, 271, 274 S Saccule, 274, 286 Saline, 256, 274 Saliva, 274 Salivary, 143, 234, 263, 274, 280 Salivary glands, 234, 274 Saponins, 225, 274, 279 Schizoid, 274, 287 Schizophrenia, 274, 275, 287 Schizotypal Personality Disorder, 274, 287 Sciatic Nerve, 275, 282 Scleroderma, 141, 256, 275 Sclerosis, 141, 151, 258, 275 Screening, 22, 30, 38, 228, 275, 284 Scrotum, 25, 275, 281 Sebaceous, 251, 275 Sebaceous gland, 251, 275 Secondary tumor, 255, 275 Secretion, 13, 66, 120, 141, 228, 238, 246, 249, 250, 252, 257, 275, 285 Secretory, 143, 275, 280 Sedative, 218, 247, 275 Sediment, 145, 275, 284 Segregation, 222, 275 Self Care, 163, 167, 215, 275 Self-Help Groups, 112, 127, 275 Semen, 144, 236, 269, 275 Sensibility, 218, 247, 275 Sensitization, 27, 39, 56, 62, 68, 275 Sensor, 159, 275 Sepsis, 157, 276 Sequence Homology, 264, 276 Sequencing, 54, 267, 276 Serologic, 248, 276 Serotonin, 154, 218, 265, 272, 276, 284 Serous, 238, 276 Serum, 62, 72, 149, 216, 217, 218, 220, 229, 253, 256, 272, 276, 284 Sex Characteristics, 261, 271, 276, 281 Sexually Transmitted Diseases, 98, 194, 276

Shedding, 66, 276 Shock, 153, 218, 276, 283 Sialyltransferases, 244, 276 Side effect, 49, 53, 149, 150, 177, 179, 196, 197, 201, 216, 223, 227, 232, 266, 276, 283 Signal Transduction, 265, 276 Signs and Symptoms, 10, 157, 273, 276 Sitz Bath, 13, 139, 277 Skeletal, 232, 257, 258, 277, 278 Skeleton, 215, 251, 269, 277 Skull, 232, 277, 281 Sleep Deprivation, 6, 277 Small intestine, 226, 228, 236, 246, 247, 250, 277 Smooth muscle, 63, 80, 118, 151, 155, 156, 218, 225, 231, 246, 257, 277, 278, 280 Sneezing, 276, 277, 279 Social Environment, 271, 277 Social Isolation, 159, 274, 277 Social Support, 12, 14, 277 Social Work, 200, 277 Sodium, 23, 40, 104, 107, 138, 139, 142, 164, 172, 176, 179, 277 Solid tumor, 219, 236, 277 Soma, 277 Somatic, 28, 39, 58, 59, 255, 256, 265, 277 Somatomedins, 250, 277 Sound wave, 230, 278 Spasm, 101, 155, 220, 255, 278 Spasmodic, 215, 278 Spastic, 100, 147, 251, 278 Spasticity, 278 Spatial disorientation, 235, 278 Specialist, 203, 234, 278 Specificity, 5, 39, 108, 217, 278 Spectrum, 7, 30, 39, 49, 50, 58, 158, 168, 252, 278 Sperm, 228, 267, 278, 281 Spermatozoa, 275, 278 Sphincter, 28, 151, 278 Spinal cord, 37, 227, 237, 239, 242, 255, 259, 265, 272, 275, 278, 280 Spinal Nerves, 265, 278 Staging, 57, 278 Statistically significant, 22, 278 Stem cell transplantation, 65, 278 Stem Cells, 65, 278, 279 Sterile, 33, 58, 142, 168, 279 Sterility, 232, 249, 279 Steroid, 139, 231, 232, 261, 274, 279 Stimulant, 178, 246, 279

302 Interstitial Cystitis

Stimulus, 40, 236, 239, 249, 250, 251, 272, 279, 281 Stomach, 4, 141, 215, 234, 239, 242, 246, 252, 258, 263, 264, 265, 272, 277, 279 Stool, 248, 251, 252, 279 Strand, 267, 279 Streptococcal, 143, 279 Streptococcus, 142, 279 Stress incontinence, 159, 279 Stricture, 64, 151, 279 Stroke, 135, 184, 191, 279 Stromal, 237, 279 Stupor, 252, 258, 279 Subacute, 65, 249, 279 Subarachnoid, 241, 245, 279 Subclinical, 249, 279 Subcutaneous, 144, 236, 261, 280 Submaxillary, 238, 280 Subspecies, 278, 280 Substance P, 150, 255, 272, 275, 280 Succinimides, 35, 280 Superoxide, 155, 280 Support group, 18, 20, 211, 280 Suppression, 34, 280 Sympathetic Nervous System, 221, 280 Sympathomimetic, 153, 235, 239, 260, 280 Symphysis, 269, 280 Symptomatic, 9, 15, 16, 18, 33, 104, 107, 146, 154, 161, 280 Symptomatic treatment, 104, 107, 280 Symptomatology, 14, 20, 59, 75, 109, 173, 280 Synapsis, 280 Synaptic, 37, 276, 280 Synaptic Transmission, 37, 280 Synergistic, 281, 282 Systemic lupus erythematosus, 80, 81, 100, 149, 256, 281 Systolic, 245, 247, 281 T Tachykinins, 150, 281 Tear Gases, 251, 281 Temporal, 59, 68, 245, 281 Teratogenic, 234, 281 Testicles, 275, 281 Testis, 239, 261, 281 Testosterone, 57, 155, 161, 215, 241, 272, 281 Tetrodotoxin, 27, 28, 281 Therapeutics, 45, 65, 119, 120, 179, 281 Thermal, 59, 235, 260, 267, 281 Third Ventricle, 247, 281

Thorax, 215, 254, 281 Threonine, 264, 281 Threshold, 40, 239, 247, 281 Thrombin, 240, 266, 267, 270, 281, 282 Thrombocytopenia, 266, 282 Thrombolytic, 144, 282 Thrombomodulin, 270, 282 Thrombosis, 144, 222, 270, 279, 282 Thromboxanes, 221, 236, 282 Thrombus, 231, 249, 267, 282 Thymidine, 83, 101, 282 Thymidine Phosphorylase, 101, 282 Tibial Nerve, 127, 275, 282 Tic, 94, 282 Tin, 5, 263, 282 Tinnitus, 5, 282, 286 Tissue Culture, 143, 282 Tissue Extracts, 43, 282 Tomography, 57, 282 Topical, 134, 139, 144, 160, 178, 221, 263, 282, 287 Topoisomerase inhibitors, 260, 283 Toxic, iv, 34, 45, 222, 232, 233, 237, 238, 248, 259, 260, 283 Toxicity, 34, 236, 237, 255, 283 Toxicology, 45, 186, 283 Toxins, 67, 220, 237, 243, 249, 257, 283 Trace element, 282, 283 Transcutaneous, 19, 25, 124, 127, 172, 176, 283 Transduction, 42, 72, 276, 283 Transfection, 223, 283 Transitional cell carcinoma, 158, 283 Transitional cells, 88, 283 Translating, 35, 283 Translation, 33, 40, 283 Translational, 47, 56, 69, 283 Transmitter, 215, 235, 251, 254, 260, 283 Transplantation, 157, 228, 248, 254, 283 Transurethral, 82, 124, 158, 283 Trauma, 71, 143, 147, 258, 283 Treatment Outcome, 52, 283 Triage, 13, 283 Tricyclic, 18, 139, 172, 218, 236, 284 Tropism, 32, 284 Tryptophan, 229, 276, 284 Tubal ligation, 105, 284 Tumor marker, 223, 284 Tumor Necrosis Factor, 33, 68, 284 Tumour, 242, 284 Tyrosine, 235, 265, 284

Index 303

U Ulcer, 22, 84, 92, 128, 150, 167, 233, 244, 284 Ulceration, 138, 233, 284 Ulcerative colitis, 90, 119, 249, 284 Unconscious, 219, 234, 247, 284 Urea, 40, 147, 178, 262, 284 Uremia, 273, 284 Ureter, 64, 71, 252, 273, 283, 284 Urethra, 19, 27, 28, 64, 139, 175, 222, 264, 269, 283, 284, 285 Urethritis, 18, 164, 284 Urinalysis, 12, 284 Urinary Retention, 151, 199, 284 Urinary tract infection, 47, 54, 56, 66, 114, 139, 140, 146, 157, 167, 222, 285 Urinary urgency, 11, 17, 22, 29, 33, 47, 58, 71, 140, 149, 156, 176, 200, 201, 212, 285 Urinate, 8, 12, 25, 160, 167, 175, 200, 212, 284, 285, 287 Urine, 10, 17, 18, 21, 24, 25, 27, 33, 39, 40, 43, 45, 53, 54, 56, 58, 61, 62, 65, 66, 70, 71, 72, 74, 77, 82, 83, 85, 86, 88, 89, 108, 114, 115, 118, 121, 138, 141, 143, 145, 146, 147, 151, 152, 157, 159, 160, 166, 167, 168, 172, 174, 194, 200, 222, 223, 232, 235, 238, 244, 245, 248, 256, 270, 273, 279, 284, 285 Urine Testing, 194, 285 Urodynamic, 5, 16, 29, 48, 52, 77, 78, 114, 115, 148, 172, 285 Urogenital, 155, 157, 243, 244, 285 Urogenital Diseases, 285 Urologic Diseases, 169, 193, 285 Urologist, 13, 17, 24, 176, 200, 285 Urothelium, 22, 27, 28, 31, 43, 47, 55, 60, 64, 67, 68, 71, 140, 285 Urticaria, 141, 218, 227, 247, 285 Uterine Contraction, 263, 285 Uterus, 231, 237, 240, 247, 255, 260, 262, 268, 273, 284, 285 V Vaccine, 30, 54, 216, 270, 285 Vacuoles, 237, 262, 285 Vagina, 19, 139, 155, 175, 225, 234, 255, 273, 285, 287 Vaginal, 138, 139, 167, 285, 287 Vaginitis, 9, 18, 138, 139, 225, 285 Valves, 157, 285

Vascular, 22, 46, 65, 72, 89, 115, 142, 218, 225, 238, 244, 245, 249, 260, 261, 266, 282, 285 Vascular endothelial growth factor, 72, 285 Vasoactive, 65, 72, 286 Vasodilatation, 148, 286 Vasodilator, 224, 225, 235, 246, 286 Vector, 283, 286 Vein, 251, 260, 286 Venous, 144, 222, 245, 261, 270, 286 Venules, 224, 238, 286 Verapamil, 147, 286 Vertebrae, 278, 286 Vesicular, 42, 286 Vestibular, 139, 286 Vestibule, 138, 139, 274, 286 Vestibulocochlear Nerve, 282, 286 Vestibulocochlear Nerve Diseases, 282, 286 Veterinary Medicine, 185, 286 Viral, 237, 283, 286 Virulence, 54, 142, 221, 283, 286 Virus, 65, 68, 222, 227, 243, 244, 250, 283, 286 Viscera, 73, 277, 286 Visceral, 7, 28, 58, 59, 62, 68, 73, 221, 286 Visual field, 224, 262, 286 Vitro, 44, 63, 71, 143, 246, 286 Vivo, 44, 57, 63, 287 Void, 21, 22, 55, 151, 200, 287 Volition, 251, 287 Vulva, 18, 139, 287 W Weight Gain, 154, 287 White blood cell, 146, 160, 219, 222, 252, 254, 257, 260, 266, 287 Withdrawal, 154, 287 Wound Healing, 60, 65, 144, 159, 228, 254, 287 X Xenograft, 219, 287 X-ray, 241, 260, 271, 287 Y Yeasts, 225, 242, 265, 287 Z Zinc Oxide, 139, 287 Zymogen, 270, 287

304 Interstitial Cystitis

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

Cystitis - 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

Influenza A - 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

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

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

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

Pubic Lice: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Breech Birth: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Naproxen Sodium: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Motrin: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cystocele: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Irbesartan: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Batten Disease: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Endometrioma: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Aromasin: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Tricor: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cretinism: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Capital Punishment: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Malepattern Baldness: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cylert: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lowprotein Diet: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lodine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Omnicef: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Birth Injuries: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Heart Palpitations: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Norwalk Virus Infection: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Impacted Teeth: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Cystitis - 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

Influenza A - 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

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

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

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

Pubic Lice: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Breech Birth: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Naproxen Sodium: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Motrin: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cystocele: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Irbesartan: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Batten Disease: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Endometrioma: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Aromasin: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Tricor: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cretinism: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Capital Punishment: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Malepattern Baldness: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cylert: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lowprotein Diet: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lodine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Omnicef: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Birth Injuries: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Heart Palpitations: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Norwalk Virus Infection: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Impacted Teeth: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

Recommend Documents