Irritable Bowel Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

IRRITABLE BOWEL SYNDROME A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENC...

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IRRITABLE BOWEL SYNDROME A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©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., 1960Irritable Bowel Syndrome: 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: 0-597-83946-8 1. Irritable Bowel Syndrome-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on irritable bowel syndrome. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON IRRITABLE BOWEL SYNDROME ................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Irritable Bowel Syndrome ........................................................... 27 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 64 CHAPTER 2. NUTRITION AND IRRITABLE BOWEL SYNDROME ..................................................... 109 Overview.................................................................................................................................... 109 Finding Nutrition Studies on Irritable Bowel Syndrome .......................................................... 109 Federal Resources on Nutrition ................................................................................................. 117 Additional Web Resources ......................................................................................................... 117 CHAPTER 3. ALTERNATIVE MEDICINE AND IRRITABLE BOWEL SYNDROME ............................... 119 Overview.................................................................................................................................... 119 National Center for Complementary and Alternative Medicine................................................ 119 Additional Web Resources ......................................................................................................... 119 General References ..................................................................................................................... 126 CHAPTER 4. DISSERTATIONS ON IRRITABLE BOWEL SYNDROME ................................................. 127 Overview.................................................................................................................................... 127 Dissertations on Irritable Bowel Syndrome ............................................................................... 127 Keeping Current ........................................................................................................................ 128 CHAPTER 5. CLINICAL TRIALS AND IRRITABLE BOWEL SYNDROME ............................................ 129 Overview.................................................................................................................................... 129 Recent Trials on Irritable Bowel Syndrome ............................................................................... 129 Keeping Current on Clinical Trials ........................................................................................... 131 CHAPTER 6. PATENTS ON IRRITABLE BOWEL SYNDROME ............................................................ 133 Overview.................................................................................................................................... 133 Patents on Irritable Bowel Syndrome ........................................................................................ 133 Patent Applications on Irritable Bowel Syndrome..................................................................... 151 Keeping Current ........................................................................................................................ 182 CHAPTER 7. BOOKS ON IRRITABLE BOWEL SYNDROME ............................................................... 183 Overview.................................................................................................................................... 183 Book Summaries: Federal Agencies............................................................................................ 183 Book Summaries: Online Booksellers......................................................................................... 186 The National Library of Medicine Book Index ........................................................................... 191 Chapters on Irritable Bowel Syndrome ...................................................................................... 191 Directories.................................................................................................................................. 196 CHAPTER 8. MULTIMEDIA ON IRRITABLE BOWEL SYNDROME ..................................................... 199 Overview.................................................................................................................................... 199 Video Recordings ....................................................................................................................... 199 Bibliography: Multimedia on Irritable Bowel Syndrome ........................................................... 201 CHAPTER 9. PERIODICALS AND NEWS ON IRRITABLE BOWEL SYNDROME .................................. 203 Overview.................................................................................................................................... 203 News Services and Press Releases.............................................................................................. 203 Newsletters on Irritable Bowel Syndrome.................................................................................. 207 Newsletter Articles .................................................................................................................... 207 Academic Periodicals covering Irritable Bowel Syndrome......................................................... 210 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 211 Overview.................................................................................................................................... 211 U.S. Pharmacopeia..................................................................................................................... 211 Commercial Databases ............................................................................................................... 212

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APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 217 Overview.................................................................................................................................... 217 NIH Guidelines.......................................................................................................................... 217 NIH Databases........................................................................................................................... 219 Other Commercial Databases..................................................................................................... 222 APPENDIX B. PATIENT RESOURCES ............................................................................................... 223 Overview.................................................................................................................................... 223 Patient Guideline Sources.......................................................................................................... 223 Finding Associations.................................................................................................................. 235 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 237 Overview.................................................................................................................................... 237 Preparation................................................................................................................................. 237 Finding a Local Medical Library................................................................................................ 237 Medical Libraries in the U.S. and Canada ................................................................................. 237 ONLINE GLOSSARIES................................................................................................................ 243 Online Dictionary Directories ................................................................................................... 245 IRRITABLE BOWEL SYNDROME DICTIONARY ................................................................ 247 INDEX .............................................................................................................................................. 325

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with irritable bowel syndrome 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 irritable bowel syndrome, 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 irritable bowel syndrome, 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 irritable bowel syndrome. 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 irritable bowel syndrome, 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 irritable bowel syndrome. The Editors

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

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CHAPTER 1. STUDIES ON IRRITABLE BOWEL SYNDROME Overview In this chapter, we will show you how to locate peer-reviewed references and studies on irritable bowel syndrome.

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

Irritable Bowel Syndrome: Still Far from a Positive Diagnosis Source: Digestive Diseases and Sciences. 37(2): 164-167. February 1992. Summary: A scoring system has been proposed for the positive diagnosis of irritable bowel syndrome (IBS) where more than 44 points excluded organic digestive disease. This article reports on a study that attempted to determine the usefulness of this scoring system in a different setting. Patients (1257) consecutively referred to the authors' medical division were admitted to the study and 270 of these, complaining of abdominal symptoms, were scored on the Kruis system method. The positive predictive value and the sensitivity of the system did not appear to be adequate. The negative predictive value and the specificity gave higher results, but did not identify 11 cases of organic

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digestive diseases. The authors conclude that the scoring system may be useful only as a first step in a diagnostic flow chart. 4 tables. 5 references. (AA-M). •

Antibiotic Use, Childhood Affluence and Irritable Bowel Syndrome (IBS) Source: European Journal of Gastroenterology and Hepatology. 10(1): 59-62. January 1998. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866. Summary: Antibiotics cause well-defined short-lived disturbances in bowel habits. There is evidence to suggest that antibiotics may play a role in the pathogenesis of irritable bowel syndrome (IBS). This article reports on a study that consisted of a survey examining the relationship between drug use and other epidemiological correlates of IBS. Subjects were 421 people (46 percent male, mean age 47 years) attending a general practice health screening clinic. Subjects were interviewed by a research nurse and completed a previously validated questionnaire. IBS symptoms were said to be present if abdominal pain with two or more Manning criteria symptoms occurred more than once a month over the previous 6 months. Results showed 48 subjects with symptoms of IBS. The following were strongly related to its presence: antibiotic use, female sex, childhood living density of less than 1 person per room, and a manual occupation for the father. The use of nonsteroidal anti-inflammatory drugs, H2 antagonists, or other types of medication was not greater in this group. The authors conclude that antibiotic use is associated with IBS and call for further research into this association. In addition, privileged childhood living conditions were also an important risk factor consistent with an allergic etiology for IBS. 2 tables. 12 references. (AA).

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Diarrhea-Constipation-Pain: When is It Irritable Bowel Syndrome? Source: Consultant. 41(8): 1089-1091, 1095-1096. July 2001. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: Central to the diagnosis of irritable bowel syndrome (IBS) are the symptoms of abdominal pain and disordered defecation of at least 3 months' duration. This article helps physicians determine when the symptoms of diarrhea, or constipation, or pain are indeed due to IBS. Either diarrhea or constipation can predominate, although the defecation pattern may vary from day to day in some patients. In the absence of evidence of more serious disease, diagnosis is based largely on the results of a thorough history and examination. For most patients, general screening tests include a complete blood cell count, erythrocyte sedimentation rate, serum chemistry panel, stool guaiac test, and stool examination for ova (eggs) and parasites. For patients older than 50 years, flexible sigmoidoscopy, colonoscopy, or barium enema may be indicated. Management of IBS consists of patient education and reassurance; dietary modification, including increased fiber intake in patients with constipation; and in some cases, judicious use of medications or psychological interventions. 2 tables. 35 references.

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Impact of Irritable Bowel Syndrome on Health-Related Quality of Life Source: Gastroenterology. 119(3): 654-660. September 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: Few data are available to evaluate health related quality of life (HRQOL) of people with irritable bowel syndrome (IBS). This article reports on a study that evaluated and compared the impact of IBS on HRQOL using previously reported HRQOL data for the United States general population and for people with selected chronic diseases. Using the SF 36 Health Survey, the authors compared the HRQOL of IBS patients (n = 877) with previously reported SF 36 data for the general U.S. population and for patients with gastroesophageal reflux disease (GERD), diabetes mellitus, depression, and dialysis-dependent end stage renal disease (ESRD). On all 8 SF 36 scales, IBS patients had significantly worse HRQOL than the U.S. general population. Compared with GERD patients, IBS patients scored significantly lower on all SF 36 scales except physical functioning. Similarly, IBS patients had significantly worse HRQOL on selected SF 36 scales than patients with diabetes mellitus and ESRD. IBS patients had significantly better mental health SF 36 scale scores than patients with depression. The authors conclude that IBS patients experience significant impairment in HRQOL. Decrements in HRQOL are most pronounced in energy and fatigue, role limitations caused by physical health problems, bodily pain, and general health perceptions. 3 figures. 4 tables. 44 references. •

Symptomatic Presentations of the Irritable Bowel Syndrome Source: Gastroenterology Clinics of North America. 20(2): 235-247. June 1991. Summary: Functional gastrointestinal disorders have no reliable physiologic, biochemical, or structural markers, therefore, they must be defined by their symptoms. This article discusses the classification of functional bowel disorders and describes the symptoms, particularly those of irritable bowel syndrome (IBS). Possible mechanisms underlying the symptoms are also mentioned. Disorders discussed include psychological disorders, IBS, burbulence, functional constipation, functional diarrhea, and unspecified functional bowel disorder. 1 figure. 2 tables. 71 references.

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High-Fiber Diet Supplementation in Patients with Irritable Bowel Syndrome (IBS): A Multicenter, Randomized, Open Trial Comparison Between Wheat Bran Diet and Partially Hydrolyzed Guar Gum (PHGG) Source: Digestive Diseases and Sciences. 47(8): 1697-1704. August 2002. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Distribution Centre, P.O. Box 322, 3300 AH Dordrecht, The Netherlands. 31 78 6392392. Fax: 31 78 6546474. E-mail: [email protected]. Summary: High fiber diet supplementation is commonly used in irritable bowel syndrome (IBS), although it poses several management problems. Partially hydrolyzed guar gum (PHGG) has shown beneficial effects in animal and human studies, but its potential role in IBS symptom relief has not been evaluated. This article reports on a study that investigated PHGG in IBS patients and compared it to a wheat bran diet. Abdominal pain, bowel habits, and subjective overall rating were longitudinally evaluated in 188 adults IBS patients (138 women, 49 men) for 12 weeks. Patients were classified as having diarrhea predominant, constipation predominant, or changeable bowel habits and were randomly assigned to PHGG or wheat bran. After four weeks, patients were allowed to switch group, depending on their subject evaluation of their symptoms. Significantly more patients switched from fiber to PHGG (49.9 percent) than from PHGG to fiber (10.9 percent) at four weeks. Per protocol analysis showed that both

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fiber and PHGG were effective in improving pain and bowel habits, but no difference was found between the two groups. Intention-to-treat analysis showed a significantly greater success in the PHGG groups (60 percent) than in the fiber group (40 percent). In conclusion, improvements in core IBS symptoms (abdominal pain and bowel habits) were observed with both bran and PHGG, but the latter was better tolerated and preferred by patients, revealing a higher probability of success than bran and a lower probability of patients abandoning the prescribed regimen. 3 tables. 43 references. •

Psychophysiological Factors Associated with Irritable Bowel Syndrome Source: Gastroenterology Nursing. 17(2): 61-67. September-October 1994. Summary: In this article, the author reviews the psychophysiological factors associated with irritable bowel syndrome (IBS). The author addresses gastrointestinal neuroendocrinology; the effects of stress on gastrointestinal motility; and the nursing implications related to this syndrome. The mechanisms underlying the etiology of IBS remain to be elucidated. However, the author suggests that IBS is a stress-induced syndrome that involves the complex interactions between external or internal stressors, the central nervous system, and the enteric nervous system. 1 figure. 1 table. 44 references. (AA-M).

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Serotonin-Transporter Polymorphism Pharmacogenetics in Diarrhea-Predominant Irritable Bowel Syndrome Source: Gastroenterology. 123(2): 425-432. August 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Irritable bowel syndrome (IBS) affects approximately 15 percent of adults, causes abdominal pain, discomfort, and altered bowel habits, and predominantly affects women. This article reports on a study of the use of serotonin (5HT) receptor antagonists in women with diarrhea- predominant IBS (DIBS). 5HT undergoes reuptake by a transporter protein (SERT). In the study, 30 patients (15 men, 15 women) with DIBS received 1 milligram twice a day of alosetron for 6 weeks; colonic transit was measured by scintigraphy at baseline and at the end of treatment. Results showed that SERT polymorphisms tended to be associated with colonic transit response; there was a greater response in those with long homozygous than heterozygous polymorphisms. Age, gender, and duration of IBS were not significantly different in the three groups (long, short, heterozygous). The authors conclude that genetic polymorphisms at the SERT promoter influence response to a 5HT antagonist in DIBS and may influence benefit to risk ratio with this class of compounds. 3 figures. 1 table. 57 references.

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Compliance, Tone and Sensitivity of the Rectum in Different Subtypes of Irritable Bowel Syndrome Source: Neurogastroenterology and Motility. 14(3): 241-247. June 2002. Contact: Available from Blackwell Science, Ltd. Journal Subscriptions, P.O. Box 88, Oxford OX2 OEL, UK. +44 1865 206180 Fax +44 1865 206219. E-mail: [email protected]. Summary: Irritable bowel syndrome (IBS) consists of various subtypes; it is unknown whether these subtypes share a common pathophysiology. Evaluation of motor and sensory function of the rectum using a barostat may help to explore a common pathophysiological background or differences in pathophysiology in subtypes of BIS.

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This article reports on a study in which authors evaluated compliance, tone, and sensitivity of the rectum, in both fasting state and postprandially (after a meal), using a computerized barostat in 15 patients with diarrhea-predominant IBS (IBSD), 14 patients with constipation-predominant IBS (IBSC), and 12 healthy controls. Rectal compliance was decreased in both IBS groups compared with controls. The perception of urge was increased only in IBSD patients, whereas pain perception was significantly increased in both IBS groups. Spontaneous adaptive relaxation was decreased in IBSD patients. Postprandially, rectal volume decreased significantly in the controls and in IBSD patients, but not in IBSC patients. In conclusion, both rectal motor and sensory characteristics are different between IBSD and IBSC patients. Therefore, testing of rectal visceroperception, adaptive relaxation, and the rectal response to a meal may help distinguish groups of patients with different subtypes of IBS. 5 figures. 2 tables. 23 references. •

Advances in the Management of Irritable Bowel Syndrome Source: Journal of Gastroenterology and Hepatology. 17(4): 503-507. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Irritable bowel syndrome (IBS) is a chronic, relapsing disorder of brain-gut regulation that can have disabling symptoms that significantly affect daily life. Recent advances in different aspects of IBS have led to a need to reassess the overall management of this common, complex disorder. Important areas include: first, the heterogeneity of symptom patterns and the role of specific diagnostic symptom criteria for use in both clinical practice and in clinical research; second, the growing interest in the potential interaction between 'peripheral' and 'central' pathophysiological mechanisms; and third, the development of new and effective drugs designed to target specific receptor systems in the enteric nervous system. This review article covers each of these aspects and emphasizes an approach to the management of patients based on pathophysiological considerations. 1 figure. 2 tables. 15 references.

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Epidemiology of Irritable Bowel Syndrome in Chinese Source: Digestive Diseases and Sciences. 47(11): 2621-2624. November 2002. Contact: Available from Kluwer Academic Publishers. Customer Service Department, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Distribution Centre, P.O. Box 322, 3300 AH Dordrecht, The Netherlands. 31 78 6392392. Fax: 31 78 6546474. E-mail: [email protected]. Summary: Irritable bowel syndrome (IBS) is common in Caucasians and Japanese persons, but its epidemiology has not been studied in urbanized Chinese populations. This study compares diagnostic criteria and explores the epidemiology of IBS in Hong Kong Chinese. In all, 964 subjects from public housing and 334 subjects from private housing were recruited for face-to-face interviews in Shatin, Hong Kong. A structured questionnaire was used to measure the prevalence of IBS. The prevalence of IBS, based on the Rome II criteria, was 3.6 percent in men and 3.8 percent in women. Men with IBS had significantly lower vitality scores on the SF-36 scale than the controls and women with IBS had significantly lower mental health scores than controls. The authors conclude that IBS is quite prevalent in Hong Kong Chinese and the quality of life of subjects with IBS is significantly affected. 3 tables. 35 references.

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Use of Antidepressants in Irritable Bowel Syndrome Source: Practical Gastroenterology. 26(3): 13-14, 19-20, 22-23, 27. March 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Irritable bowel syndrome (IBS) is the most common bowel disorder seen in gastroenterology practice. IBS is characterized by a pattern of waxing and waning abdominal pain, bloating, and disturbance of bowel habits. This article describes the rationale for the use of antidepressants in IBS, the results of clinical trials, suggested treatment plan, and directions for future research. The authors note that IBS is a complex biopsychosocial disorder whose precise pathophysiology is unknown, although it is generally accepted that abnormal brain-gut interactions play a major role. At the time of clinical presentation, about 50 percent of IBS patients have a definable psychiatric disorder. Psychosocial stressors have been demonstrated to have an important modulatory role in IBS, affecting not only the illness experience but also health care seeking behavior and the clinical outcome. Antidepressants represent an attractive therapeutic approach for the treatment of IBS, not only for their psychotropic effects, but also for their neuromodulatory and analgesic properties. However, there is still a lack of well-designed, appropriately powered, randomized clinical trials examining the use of antidepressants in IBS. 1 figure. 4 tables. 51 references.

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Irritable Bowel Syndrome: Streamlining the Diagnosis Source: Postgraduate Medicine. 102(3): 197-198, 201-204, 207-208. September 1997. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: Irritable bowel syndrome (IBS), a common gastrointestinal disorder, is the condition for which patients are most often referred to gastroenterologists. Symptoms may be distressing enough to cause avoidance of work and social activities. Stress often exacerbates symptoms, and sensory abnormalities are common in patients with the disease. In this article, the authors describe how careful history taking and physical examination can avoid the overuse of diagnostic testing and point to the most effective treatment. Differential diagnosis for IBS includes consideration of many common gastrointestinal illnesses, including parasitic infections, salmonellosis, celiac sprue (gluten intolerance), chronic pancreatitis, Crohn's disease, ulcerative colitis, peptic ulcer disease, colon cancer, Campylobacter jejuni infection, and endometriosis. A strong physician-patient relationship at the time of IBS diagnosis improves the patient's ability to cope with the disease and reduces the number of subsequent office visits. The physician needs to involve the patient as a collaborative partner in the decision-making process and to avoid extensive invasive procedures if there is no firm indication for them. The patient's concerns and fears need to be addressed. Dietary changes, specifically elimination of troublesome foods, such as sorbitol, alcohol, caffeine, fats, legumes, sugar and, in lactose-intolerant patients, milk products, may benefit IBS patients. Relief of colonic spasm may be obtained with short-acting anticholinergics and other antispasmodic medications. Loperamide may also prove to be beneficial, especially in reducing post-meal diarrhea. Antidepressants are now being evaluated as potential therapeutic agents for IBS. One sidebar lists sources of information on IBS for physicians and patients, including organizations and Internet sites. 1 figure. 1 table. 21 references. (AA-M).

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Does a Physically Active Lifestyle Improve Symptoms in Women with Irritable Bowel Syndrome? Source: Gastroenterology Nursing. 24(3): 129-137. May-June 2001. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: It has been proposed that physical activity moderates physiological or psychological responses to chronic conditions. This article reports on a study undertaken to determine if women with a chronic functional gastrointestinal (GI) disorder (irritable bowel syndrome, or IBS) had less active lifestyles than healthy controls. The study also tested whether active women with IBS had less severe recalled or daily reports of GI, psychological, and somatic symptoms than inactive women with irritable bowel syndrome. Questionnaires were used to measure GI and psychological distress and somatic symptoms in 89 women who participated in the study. A daily symptom and activity diary was kept for one menstrual cycle. Women with IBS were significantly less likely to be active (48 percent) than control women (71 percent). Within the IBS group, active women were less likely to report a feeling of incomplete evacuation following a bowel movement than inactive women, yet active women did not have less severe recalled psychological or somatic symptoms than inactive women. Active women with IBS reported less severe daily somatic symptoms, which were accounted for by a lower level of fatigue, but not daily GI or psychological symptoms. These results suggest that physical activity may produce select symptom improvement in women with IBS. 4 tables. 55 references.

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Naloxone Treatment for Irritable Bowel Syndrome: A Randomized Controlled Trial with an Oral Formulation Source: Alimentary Pharmacology and Therapeutics. 16(9): 1649-1654. September 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Opioids change gut motility and secretion, causing delayed intestinal transit and constipation. Endorphins play a role in the constipation troubling some patients with irritable bowel syndrome (IBS); hence naloxone, an opioid antagonist, may have a therapeutic role. This article reports on a study undertaken to assess the efficacy and safety of an oral formulation of naloxone in IBS patients with constipation. The randomized, double-blind, placebo-controlled trial included 25 patients with IBS (constipation-predominant and alternating types) who received 8 weeks of treatment with naloxone capsules, 10 milligrams twice daily, or identical placebo. Adequate symptomatic relief was recorded in six of 14 on naloxone and three of 11 on placebo. Whilst the differences were not significant, improvements in severity gradings and mean symptom scores for pain, bloating, straining and urgency to defecate were greater with naloxone than placebo for all parameters. In addition, quality of life assessments improved to a greater extent in patients taking naloxone. The authors conclude that preliminary results suggest that naloxone is well tolerated and beneficial in patients with irritable bowel syndrome and constipation. A larger clinical trial is needed to provide sufficient statistical power to assess efficacy. 4 figures. 2 tables. 29 references.

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Double-Blind Study of Nicardipine in Irritable Bowel Syndrome Source: European Journal of Gastrenterology and Hepatology. 3(2): 181-184. February 1991. Summary: Previous studies have suggested that calcium antagonists inhibit colonic motility and therefore may have therapeutic potential in irritable bowel syndrome (IBS). This article reports on a double-blind cross-over trial of the calcium antagonist nicardipine in 62 patients with IBS. Nicardipine significantly decreased whole gut transit time in constipated patients, but there was no effect on transit time in those with diarrhea, or on those with an alternating bowel habit. However, significant effects on general well-being, abdominal pain, abdominal distension or bowel habit were not observed. The authors conclude that this study suggests that nicardipine does not have a useful therapeutic effect in irritable bowel syndrome. 1 figure. 2 tables. 19 references. (AA-M).

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Irritable Bowel Syndrome and Psychiatric Illness Source: American Journal of Psychiatry. 147(5): 565-572. May 1990. Summary: Psychiatric illnesses such as mood, anxiety, and somatization disorders share many common features with irritable bowel syndrome. The authors of this article review recent developments in the definition of irritable bowel syndrome (IBS) and its relationship to psychiatric illness, discuss the diagnostic validity of IBS from several perspectives, and offer a pathophysiological model of IBS that integrates many of the biological and psychosocial findings of earlier studies. Psychiatric evaluation appears to be an important factor in the diagnosis and treatment of patients with IBS. 1 table. 96 references. (AA).

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Anxiety and the Irritable Bowel Syndrome: Psychiatric, Medical, or Both? Source: Journal of Clinical Psychiatry. 58(supplement 3): 51-61. 1997. Contact: Available from Physicians Postgraduate Press, Inc. P.O. Box 752870, Memphis, TN 38175-2870. Summary: The association between the irritable bowel syndrome (IBS) and psychiatric disorders is well-known to most clinicians, but the nature of the relationship is far from clear. There is an increased prevalence of psychiatric illness in IBS patients and an increase in IBS in psychiatric patients. Whether this association exists outside of treatment-seeking populations (i.e., in people with IBS who do not seek treatment) has not been well investigated. This article selectively reviews the existing literature regarding the association of IBS and psychiatric illness in both patient and nonpatient samples. The author presents a model of the brain-gut interaction, and offers a discussion of the practical implications of this model for treating individuals with IBS. The author considers patients with IBS and general anxiety disorder (GAD), panic disorder, posttraumatic stress disorder (PTSD), social phobia, and mood disorders. The treatment model suggests that, even in patients without psychiatric disorders, neuroactive medications may be a useful tool in improving functioning in individuals whose functional GI disorders have not responded to standard, conservative measures. Appended to the article is a discussion between three physicians on the concepts presented. 2 figures. 2 tables. 51 references. (AA-M).

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Irritable Bowel Syndrome: Managing the Patient With Abdominal Pain and Altered Bowel Habits Source: Medical Clinics of North America. 79(2): 373-390. March 1995. Contact: Available from W.B. Saunders Company, Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: The authors of this article outline the management of the patient with irritable bowel syndrome (IBS), particularly for abdominal pain and altered bowel habits. One goal of the article is to assist the practitioner in reaching a diagnosis of IBS efficiently by using a carefully obtained history, physical examination, and appropriate laboratory tests. The authors also hope to make the practitioner aware of advances in the understanding of pathophysiologic and psychosocial processes in IBS so that treatment may be tailored to an individual patient's needs. Specific topics include epidemiology, pathophysiology, diagnostic tests, and management, particularly the role of a supportive and empathetic physician-patient relationship. 5 tables. 107 references.

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Treatment of Irritable Bowel Syndrome Source: Alimentary Pharmacology and Therapeutics. 16(8): 1395-1406. August 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The efforts of clinical researchers, lay organizations and pharmaceutical companies have increased the public profile of irritable bowel syndrome (IBS) and made it a respectable diagnosis. Diagnostic symptom criteria encourage a firm clinical diagnosis, which is the foundation of a logical management strategy. This article reviews the treatment of IBS, emphasizing that any plan of patient care begins with education. Reassurance that no structural disease threatens should be tempered with the reality that symptoms are likely to recur over many years. Patients expect diet and lifestyle advice, even if this is not specific to irritable bowel syndrome. Only a few of those with IBS see doctors, and even fewer see specialists. Therefore, the treating physician should ascertain the reason for the visit, the patient's fears and the presence of any comorbid illness, such as depression, that might require treatment in its own right. No drug treatment is useful for all of the symptoms of IBS, and many patients require no drug at all. If used, drugs should target the predominant symptom. Most patients with IBS need psychological support. Reassurance, discussion, and relaxation techniques can be provided by the family doctor. In all cases, successful treatment depends on a confident diagnosis and the strength of the doctor-patient relationship. 1 figure. 3 tables. 100 references.

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Health-Related Quality of Life and Health Care Costs in Severe, Refractory Irritable Bowel Syndrome Source: Annals of Internal Medicine. 134(9 Part 2): 860-868. May 1, 2001. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: The irritable bowel syndrome (IBS) may lead to considerable impairment of health related quality of life (HRQOL) and high health care costs. It is not clear whether these poor outcomes directly result from severe bowel symptoms or if they reflect a

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coexisting psychiatric disorder. This article reports on a study undertaken to determine whether bowel symptom severity and psychological symptoms directly influence HRQOL and health care costs. The cross sectional survey took place at secondary and tertiary gastroenterology clinics and included 257 patients with severe IBS who did not respond to usual treatments and who were recruited for a trial of psychological treatment. Predictors were abdominal pain, entries in a diary of 10 IBS symptoms, and measures of psychological symptoms. Outcomes were inability to work, HRQOL, and health care and productivity costs. Abdominal pain occurred on average 24 days per month and activities were restricted on 145 days of the previous 12 months. The mean Hamilton depression score was 11.3 plus or minus 6.1. The physical component summary score was low and the patients had incurred high health care costs over the previous year. Global severity and somatization scores on the Symptom Checklist, abdominal pain, and Hamilton depression scores independently contributed to the physical component score, but only psychological scores were associated with disability due to ill health. These variables did not accurately predict health care or other costs. History of sexual abuse was not an independent predictor of outcome. The authors conclude that both abdominal and psychological symptoms are independently associated with impaired health related quality of life in patients with severe IBS. Optimal treatment is likely to require a holistic approach. Since health care and loss of productivity costs are not clearly associated with these symptoms, alleviation of them will not necessarily lead to reduced costs. 2 figures. 3 tables. 28 references. •

Irritable Bowel Syndrome in Twins: Heredity and Social Learning Both Contribute to Etiology Source: Gastroenterology 121(4): 799-804. October 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: The irritable bowel syndrome is a chronic functional gastrointestinal disorder characterized by abdominal discomfort or pain that beings with a change in the frequency or consistency of stool (diarrhea or constipation), that is relieved by defecation, and that is present in the absence of other diseases that could explain the symptoms. Heredity has been suggested to explain the finding that irritable bowel syndrome (IBS) tends to run in families. This article reports on a study undertaken to assess the relative contribution of genetic and environmental (social learning) influences on the development of IBS by comparing concordance rates in monozygotic (identical) and dizygotic (fraternal) twins to concordance between mothers and their children. Questionnaires soliciting information on the occurrence of more than 80 health problems, including IBS, in self and other family members were sent to both members of 11,986 twin pairs. The authors' analysis is based on 10,699 respondents representing 6,060 twin pairs. Concordance for IBS was significantly greater in monozygotic (17.2 percent) than in dizygotic (8.4 percent) twins, supporting a genetic contribution to IBS. However, the proportion of dizygotic twins with IBS who have mothers with IBS (15.2 percent) was greater than the proportion of dizygotic twins with IBS who have co-twins with IBS (6.7 percent). Logistic regression analysis showed that having a mother with IBS and having a father with IBS are independent predictors of irritable bowel status; both are stronger predictors than having a twin with IBS. Addition of information about the other twin accounted for little additional predictive power. The authors conclude that heredity contributes to development of IBS, but social learning (what an individual learns from those in his or her environment) has an equal or greater influence. 1 figure. 2 tables. 18 references.

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Review Article: An Integrated Approach to the Irritable Bowel Syndrome Source: Alimentary Pharmacology and Therapeutics. 13(Supplement 2): 3-14. May 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The medical understanding of the pathophysiology of irritable bowel syndrome (IBS) has evolved from a motility disorder to a more integrated understanding of enhanced motility and visceral hypersensitivity associated with brain gut dysfunction. This article reviews recent work that supports an integrated approach to managing IBS. Psychosocial factors contribute to the predisposition, precipitation, and perpetuation of IBS symptoms and affect the clinical outcome. Newer brain imaging techniques (MRI, PET) may help physicians understand the relationship between altered emotional states with pain enhancement and other gastrointestinal symptoms. The author recommends diagnosis using symptom based (e.g., Rome) criteria and a conservative approach. A careful history will identify the need for diagnostic studies and treatments as determined by the nature and severity of the predominant symptoms. Treatment is based on an effective relationship between physician and patient and a combined pharmacologic and behavioral approach. For most patients with mild symptoms, dietary and lifestyle changes are usually sufficient for treatment. Newer medications acting at the 5-HT receptor may help reduce pain and bowel dysfunction. For more severe pain, antidepressants may be considered. 1 figure. 2 tables. 90 references.

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Long-term Safety of Tegaserod in Patients with Constipation-Predominant Irritable Bowel Syndrome Source: Alimentary Pharmacology and Therapeutics. 16(10): 1701-1708. October 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The oral administration of the drug tegaserod causes gastrointestinal (GI) effects resulting in increased gastrointestinal motility (movement of contents through the GI tract) and attenuation of visceral sensation. This article reports on a study undertaken to determine the long term safety and tolerability of tegaserod in patients with irritable bowel syndrome (IBS) with constipation as the predominant symptom of altered bowel habits. The multicenter, open label study included 579 patients. Of these, 304 (53 percent) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhea (10.1 percent), headache (8.3 percent), abdominal pain (7.4 percent), and flatulence (5.5 percent). Forty serious adverse events were reported in 25 patients (4.4 percent of patients) leading to discontinuation in 6 patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated for the first time in this study. The authors conclude that tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant IBS. The adverse event profile, clinical laboratory evaluations, vital signs, and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12 month period. 1 figure. 4 tables. 23 references.

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Diet and the Irritable Bowel Syndrome Source: Gastroenterology Clinics of North America. 20(2): 313-324. June 1991. Summary: There is a prevailing patient perception that diet plays a key role in precipitating or perpetuating symptoms of irritable bowel syndrome (IBS). This article provides dietary information for the physician treating patients with IBS. The author focuses special attention on diagnostic and therapeutic suggestions directed toward reducing the intensity and frequency of symptoms. Topics covered include diagnostic considerations; lactose intolerance; fructose intolerance; sorbitol intolerance; and dietary considerations in functional gastrointestinal disorders including the esophagus, gastricduodenum, small bowel, colonic motor dysfunction and gas syndrome. 29 references.

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New Directions in the Irritable Bowel Syndrome Source: Gastroenterology Clinics of North America. 20(2): 335-349. June 1991. Summary: This article about irritable bowel syndrome (IBS) focuses on possible subgroups of IBS and methods of diagnosis and treatment. The authors discuss treatments of IBS based on motility disturbances, psychologic problems, dietary intolerance, hormonal imbalance, and the effects of peptides such as cholecystokinin (CCK) and motilin. The authors note that future directions for psychologic treatment of IBS will likely depend on further investigation of the relative importance of psychologic factors in the etiology of and patient response to IBS. 349 references.

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Treatment of the Irritable Bowel Syndrome Source: Gastroenterology Clinics of North America. 20(2): 325-333. June 1991. Summary: This article addresses treatment issues in the management of irritable bowel syndrome (IBS). The author stresses that although there is not a specific agent to treat IBS, once organic illness has been ruled out, a basis for therapy options can be formulated. Topics covered include psychologic factors, including stress, anxiety, depression, and the use of anti-anxiety agents; the use of antidepressant agents; anticholinergic medications; food-related factors, including gas-related agents; the treatment of functional constipation; treatment of diarrhea; and the role of the physician-patient relationship. The author concludes that careful, continued follow-up assessment of therapeutic endeavors, a sincere interest in the patient's concerns, and surveillance for intercurrent organic illness are the basics of complete ongoing care. 2 tables. 31 references.

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Irritable Bowel Syndrome: A Quick Review of a Common GI Problem Source: IM. Internal Medicine. 19(8): 24-25. August 1998. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Summary: This article briefly brings readers up-to-date on the diagnosis and treatment strategies used for irritable bowel syndrome (IBS). IBS is a functional disorder of the gastrointestinal tract that occurs in 10 to 22 percent of adults. The most common symptoms are abdominal pain and altered bowel habits, including diarrhea or constipation or a combination of the two. The author discusses pathophysiology, the criteria for confirming a diagnosis of IBS, laboratory tests that may contribute to this diagnosis of exclusion, and treatment options. Criteria for confirming a diagnosis require that symptoms be present for at least 3 months. Management begins with the

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need for the physician to establish a therapeutic relationship. Because of their safety and frequent placebo effect, a trial of fiber supplements is reasonable in all patients with IBS. The author discusses the treatments for patients in whom diarrhea predominates; those in whom pain, gas, and bloating predominate; and those in whom constipation is the primary problem. The author notes that, in all cases of IBS, regardless of the predominating symptom, the use of antidepressants, anxiolytics, and psychotherapy may be indicated for patients with associated affective disorders. 1 figure. 4 references. •

Mental Medicine for Irritable Bowel Syndrome: Treatment Approaches for IBS Source: Mental Medicine Update. 1(1): 4-5. Spring-Summer 1992. Contact: Available from Center for Health Sciences, ISHK. P.O. Box 176, Los Altos, CA 94023. (415) 948-9428. Summary: This article brings readers up-to-date on irritable bowel syndrome (IBS). Topics include the symptoms of IBS; the role of stress and other psychosocial factors; and treatment modalities, including medical treatments, diet therapy, and psychological techniques for managing stress. Techniques covered in the latter section include the use of a symptom diary, relaxation techniques, psychotherapy, and hypnosis. The article concludes with a list of six references for readers who wish to obtain more information about IBS.

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Irritable Bowel Syndrome Defined by Factor Analysis: Gender and Race Comparisons Source: Digestive Diseases and Sciences. 40(12): 2647-2655. December 1995. Summary: This article describes a study to examine the applicability across subgroups of the Manning criteria commonly used to diagnose the irritable bowel syndrome (IBS). A 22-item symptom questionnaire was administered to male and female African-American and Caucasian adults (n=1344). Consistent with the findings of a previous factor analytic study, three of the six Manning symptoms (loose stools and more frequent bowel movements with onset of pain, pain relieved by defecation) formed a cluster corresponding to the IBS in all subgroups. The researches conclude that the three core Manning symptoms have equal applicability to both genders and to African-Americans as well as to Caucasians. They are useful symptoms criteria for the diagnosis of IBS when used in conjunction with medical evaluation. 1 figure. 2 tables. 18 references. (AAM).

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Diagnosis and Treatment of Irritable Bowel Syndrome Source: American Family Physician. 55(3): 875-880. February 15, 1997. Summary: This article discusses the diagnosis and treatment of irritable bowel syndrome (IBS), a common disorder characterized by symptoms of abdominal pain with diarrhea and or constipation. IBS is associated with significant disability and health care costs. The authors advocate a practical approach to diagnosis utilizing the symptombased Rome criteria. Management of patients has been helped by recent findings relating to the pathophysiology of the disorder. Dysregulation of intestinal motor functions, sensory functions and central nervous system functions is currently believed to be the basis for IBS symptoms. Symptoms are a result of both abnormal intestinal motility and enhanced visceral sensitivity. Psychosocial factors can affect the illness experience and the clinical outcome. The authors stress that an effective physicianpatient relationship is required for a successful outcome. Individualized treatment

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involves an integrated pharmacologic and behavioral approach determined by the predominant symptom type, the severity of the symptoms, and the degree of disability. 5 tables. 11 references. (AA). •

Diagnostic Evaluation of the Irritable Bowel Syndrome Source: Gastroenterology Clinics of North America. 20(2): 269-278. June 1991. Summary: This article explores the diagnostic evaluation of Irritable Bowel Syndrome (IBS), one of the most common of all gastrointestinal disorders. Topics include a definition of IBS; diagnostic accuracy; historical features, including pain, altered bowel habits, distention, and extracolonic and extraintestinal symptoms; significant clinical features, physical findings, and laboratory features; and a philosophy of diagnosis as it applies to IBS. 4 tables. 35 references.

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Ileocecal Area and the Irritable Bowel Syndrome Source: Gastroenterology Clinics of North America. 20(2): 297-311. June 1991. Summary: This article focuses on irritable bowel syndrome (IBS) and the ileocecal area, or the ileocolonic junction (ICJ). Topics covered include a summary of the normal physiology of the region; the symptoms of IBS; the role of altered functions of the distal small bowel-proximal colon in IBS; the role of ileal and colonic contractions; regulation of the motility of the ICJ; motility-transit relationships; and IBS as a grouping of symptoms that fulfill at least three of the Manning criteria. The author conclude that the ICJ, lying as it does at the gateway between the absorptive regions of the small intestine and the storage and excretory regions of the colon, may be important in the pathophysiology of pain, bloating, and altered bowel movements in patients with IBS. 8 figures. 52 references.

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Irritable Bowel Syndrome: A Cost-Effective Approach for Primary Care Physicians Source: Postgraduate Medicine. 101(3): 215-216, 219, 220, 223-226. March 1997. Summary: This article outlines for primary care physicians a cost-effective approach to patients with irritable bowel syndrome (IBS). IBS is a symptom complex of altered bowel habits, abdominal discomfort, and the absence of detectable organic disease. The author stresses that the key to cost-effective management is identification of the characteristic symptom pattern. Topics include pathophysiologic factors, clinical features, diagnosis, treatment options, medications commonly used to treat IBS, and medications currently being developed that may be of use in IBS. The author stresses that patient education and reassurance about the benign course of the disease are important aspects of effective treatment. 1 figure. 2 tables. 20 references. (AA-M).

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Interventions for Irritable Bowel Syndrome: A Nursing Model Source: Gastroenterology Nursing. 18(6): 224-230. November-December 1995. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-6423 or (410) 528-8555. Summary: This article presents a nursing model for interventions for irritable bowel syndrome (IBS). Using the Human Response Model, the authors review intervention studies for IBS. The model provides a context for integration of Person (vulnerability) and Environment (risk) factors that may modify the patient's response to a given therapeutic regimen. Human responses are categorized as Physiological,

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Pathophysiological, and Behavioral/Experiential. The authors discuss interdisciplinary therapeutic strategies including modility manipulations via pharmacological agents, dietary modifications, and self-care enhancement. Areas for nursing research are also described. 1 figure. 1 table. 34 references. (AA-M). •

Roundtable Conference on Irritable Bowel Syndrome, Part I Source: Practical Gastroenterology. 16(8): 12, 14-18, 21. September 1992. Summary: This article presents an edited transcript of a videotaped roundtable conference on irritable bowel syndrome (IBS) sponsored by Schwarz Pharma that took place in Chicago on June 13, 1992. Roundtable participants were Marshall Sparberg; Gerald Friedman; Norton Greenberger; Marvin Schuster; and William Snape. Topics include a definition of IBS; symptoms; etiology of IBS; the emotional components of IBS; extraintestinal manifestations of IBS; the interrelationship of IBS with menstruation and with diet; foods that may trigger, perpetuate, or accentuate IBS symptoms; the importance of a food diary in diagnosis and management of IBS; lactose sensitivity; dietary fiber; the use of psyllium products; bowel motility and dietary fat; motor dysfunctions in IBS; pain in IBS; and functional versus organic disease. 10 references.

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American Gastroenterological Association Medical Position Statement: Irritable Bowel Syndrome Source: Gastroenterology. 112(6): 2118-2119. June 1997. Summary: This article presents guidelines to help physicians in the diagnosis and management of patients with irritable bowel syndrome (IBS). These guidelines were developed from a comprehensive review of the medical literature pertaining to IBS. The IBS is a combination of chronic or recurrent gastrointestinal (GI) symptoms not explained by structural or biochemical abnormalities, which is attributed to the intestines and associated with symptoms of pain and disturbed defecation and or symptoms of bloating and distension. The authors note that psychological stress exacerbates GI symptoms in everyone, but to a greater degree in patients with IBS. IBS adversely affects health-related quality of life, including impairment of physical and psychosocial function, disability, work absenteeism, and physician visits. A physical examination and the following studies are recommended for routine evaluation: complete blood count; sedimentation rate; chemistries; stool for ova, parasites, and blood; and flexible sigmoidoscopy or colonoscopy or barium enema with sigmoidoscopy if older than 50 years. The treatment strategy is based on the nature and severity of the symptoms, the degree of physiological disturbance and functional impairment, and the presence of psychosocial difficulties affecting the course of the illness. Patients with mild symptoms usually respond to education and reassurance and simple treatments not requiring prescription medication. A smaller proportion of patients with moderate symptoms have more disability and require pharmacological treatments directed at altered gut physiology or psychological treatments. 1 table. 1 reference. (AA-M).

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Roundtable Conference on Irritable Bowel Syndrome, Part II Source: Practical Gastroenterology. 16(9): 30-39. October 1992. Summary: This article presents the second part of a videotaped conference on irritable bowel syndrome (IBS) that took place in Chicago in June 1992. Topics include the symptom of painless diarrhea; the role of fatty acids; the causes of constipation; hypersensitivity of the smooth muscle of the rectum and colon; colonic motility;

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problems with excessive gas, including classification, etiology, and treatment; dealing with aerophagic patients ('air swallowers'); the role of biofeedback and other behavioral therapies; handling patients who have excessive bloating; problems with excessive rectal gas, including excessively odorous rectal gas; the role of rice and rice products in the diet; medical history and physical examination; and diagnostic tests used after the determination of IBS. 3 figures. 7 references. •

Challenge of Irritable Bowel Syndrome Source: American Family Physician. 53(4): 1229-1236. March 1996. Summary: This article provides general practitioners with an overview of irritable bowel syndrome (IBS), a common disorder with symptom complexes that can include diarrhea, constipation, pain, and bloating. Topics include epidemiology, pathophysiology, diagnosis and diagnostic criteria, treatment options, and the course to follow when initial treatment fails. Treatments include the use of dietary fiber, addressing the psychological factors involved, a bowel-training regimen, diet therapy, antispasmodic drugs, and antidepressants. The authors stress the importance of a supportive professional-patient relationship in treating patients with IBS. 4 tables. 52 references.

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Health-Related Quality of Life Among Persons With Irritable Bowel Syndrome: A Systematic Review Source: Alimentary Pharmacology and Therapeutics. 16(6): 1171-1185. June 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This article reports on a literature review undertaken with three objectives: to compare the health related quality of life (HRQoL) of patients with irritable bowel syndrome (IBS) with that of health controls; to compare the HRQoL of irritable bowel syndrome patients to those with other diseases; and to examine therapy-associated changes in HRQoL of IBS patients. Searches of all English and non English articles from 1980 to 2001 were performed in MEDLINE and EMBASE and two investigators performed independent data abstraction. Seventeen articles met the selection criteria. Thirteen studies addressed objective number one; 11 of these studies showed a significant reduction in HRQoL among IBS patients. Of these, only one study was considered of high quality. Four studies addressed objective number two, none of which was considered to be high quality in addressing this objective. Four trials (three of high quality) addressed objective number three. One of these showed that symptomatic improvement with Leupron compared to placebo was accompanied by an improvement only in the comparative health domain of the HRQoL. The second study reported significant positive changes in HRQoL after 12 weeks of cognitive behavioral therapy. The third report of two placebo controlled studies indicated significant improvement with alosetron on most domains of IBS quality of life assessment instruments. The authors conclude that there is reasonable evidence for a decrease in HRQoL in patients with moderate to severe IBS. HRQoL in IBS patients is impaired to a degree comparable to other chronic disorders such as GERD and depression. A therapeutic response in IBS related pain has a corresponding improvement in HRQoL. 4 tables. 34 references.

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Office-Based Physician Visits: A Comparison of Irritable Bowel Syndrome with Other Gastrointestinal Disorders Using National Ambulatory Medical Care Survey Data Source: Practical Gastroenterology. 26(9): 58, 60-62, 65-66, 68. September 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: This article reports on a study in which National Ambulatory Medical Care Survey data were used to compare health care resource utilization and frequency of physician visits for irritable bowel syndrome (IBS) with other functional and organic gastrointestinal (GI) disorders. IBS accounted for more than four million ambulatory office visits between 1997 and 1999. A substantial proportion of these IBS visits were by female patients, and a high percentage of the visits were to a gastroenterologist. IBS visits frequently included diagnostic or screening tests and mentions of medications. This evidence suggests that patients with IBS require considerable medical attention, which incurs substantial costs. The emergence of effective medications, as well as education of both patients and providers, may reduce resource utilization associated with IBS and facilitate the delivery of quality health care to patients. 4 figures. 3 tables. 9 references.

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Sleep Disturbance Influences Gastrointestinal Symptoms in Women with Irritable Bowel Syndrome Source: Digestive Diseases and Sciences. 45(5): 952-959. May 2000. Contact: Available from Kluwer Academic/Plenum Publishers. 233 Spring Street, New York, NY 10013-1578. (212) 620-8000. Fax (212) 807-1047. Summary: This article reports on a study that evaluated the association between sleep disturbance and gastrointestinal symptoms in women with and without irritable bowel syndrome (IBS). The study also examined the role of psychological distress in this relationship. Women with IBS (n = 82) reported considerably higher levels of sleep disturbance compared with controls (n = 35), using both retrospective 7 day recall and daily diary recall for two menstrual cycles. The authors used daily diary data to estimate the association between sleep disturbance and gastrointestinal symptoms, both across women (i.e., whether women with high average sleep disturbance have higher average gastrointestinal symptoms) and within women (i.e., whether poorer than average sleep on one night is associated with higher than average gastrointestinal symptoms the following day). The regression coefficients for the across women effect are large and highly significant in both groups. The regression coefficients for the within woman effect are considerably smaller and statistically significant only in the IBS group. These regression coefficients showed little change when daily psychological distress or stress was controlled for, the one exception being the coefficient for the across women effect in the IBS group, which decreased substantially but still remained highly significant. Because it is possible that gastrointestinal symptoms could, in fact, cause poor sleep, the authors also fitted the temporally reversed model to evaluate the association between gastrointestinal symptoms on one day and sleep disturbance that night. The authors conclude that their results are consistent with the hypothesis that poor sleep leads to higher gastrointestinal symptoms on the following day among women with IBS. 1 figure. 2 tables. 41 references.

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Abdominal Pain and Irritable Bowel Syndrome in Adolescents: A Community-Based Study Source: Journal of Pediatrics. 129(2): 220-226. August 1996. Summary: This article reports on a study to determine the prevalence of gastrointestinal (GI) symptoms, including abdominal pain in a community-based population of adolescents; whether a subgroup of these subjects have symptoms resembling irritable bowel syndrome (IBS); and whether anxiety and depression are more commonly found in adolescents with IBS-type symptoms compared with unaffected adolescents. The study included 507 subjects; abdominal pain was noted by 75 percent of all students. The pain occurred weekly in 13 to 17 percent of the subjects and was severe enough to affect activities in approximately 21 percent. IBS-type symptoms were noted by 17 percent of high school students and 8 percent of middle school students who reported abdominal pain. Anxiety and depression scores were significantly higher for students with IBS-type symptoms compared with those without symptoms. Eight percent of all students had seen a physician for abdominal pain in the previous year. These visits were correlated with abdominal pain severity, frequency, duration, and disruption of normal activities but not with anxiety, depression, gender, family structure, or ethnicity. 3 tables. 23 references. (AA-M).

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Pharmacologic Treatment of the Irritable Bowel Syndrome: A Systematic Review of Randomized, Controlled Trials Source: Annals of Internal Medicine. 133(2): 136-147. July 18, 2000. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: This article reports on a study undertaken to evaluate the efficacy of pharmacologic agents (drugs) for irritable bowel syndrome (IBS). The study featured an electronic literature search (1966 to 1999) and a manual search of references from bibliographies of identified articles. Studies chosen for inclusion were randomized, double blind, placebo controlled, parallel or crossover trials of a pharmacologic intervention for adult patients; the studies had to report outcomes of improvement in global or IBS specific symptoms. Seventy studies met the inclusion criteria. The most common medication classes were smooth muscle relaxants (16 trials), bulking agents (13 trials), prokinetic agents (6 trials), psychotropic agents (7 trials), and loperamide (4 trials). The strongest evidence for efficacy was shown for smooth muscle relaxants in patients with abdominal pain as the predominant symptom. Loperamide seems to reduce diarrhea but does not relieve abdominal pain. Although psychotropic agents were shown to produce global improvement, the evidence is based on a small number of studies of suboptimal quality. Other treatment options, including psychotropic drugs, 5 hydroxytryptamine (5 HT) receptor antagonists, peppermint oil, and Chinese herbal medicine, require further study. 3 tables. 109 references.

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Management of Irritable Bowel Syndrome: A European, Primary and Secondary Care Collaboration Source: European Jounral of Gastroenterology and Hepatology. 13(8): 933- 939. August 2001. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866 or (215) 574-2210.

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Summary: This article reports on the development of recommendations for the diagnosis and management of irritable bowel syndrome (IBS) for European doctors delivering primary medical care. These recommendations can be adapted by local medical groups according to their language, custom, and health care systems. The workshop, planned by a steering committee, was attended by 21 general practitioners and gastroenterologists from Europe. After a state of the art symposium, four working groups considered the following aspects of IBS management: what to tell the patient, diagnosis, non medical treatment, and psychosocial management. Current and future drug management was reviewed by the steering committee. The process permitted a unique dialog between general practitioners and gastroenterologists, in which it was necessary to reconcile the specialists' emphasis on thoroughness with the practical, epidemiological, and economic realities of primary care. The recommendations emphasize education of the patient, a positive symptom based diagnosis, dietary and lifestyle advice, psychological support, and a critical analysis of current specific psychological and pharmacological (drug) treatments. Patient education should be tailored to the patient's ideas, fears and expectations and should take into account their understanding of their IBS symptoms. The information can include the following elements: the symptoms are real, not imagined or merely psychological; IBS is chronic and fluctuates in severity and duration; factors that trigger symptoms are multiple and vary among patients and over time; the mind-gut link explains how stress, emotions, perceptions and thoughts can affect the symptoms; and the symptoms are not life threatening. The recommendations remind readers that some symptoms cannot be explained by IBS and should trigger further diagnosis; these include: fever, anemia, bleeding from the gut, significant weight loss, family history of cancer or inflammatory bowel disease, recent change in bowel habit, over 45 years of age, and physical findings (e.g., an abdominal mass). 2 tables. 48 references. •

Roundtable Conference on Irritable Bowel Syndrome, Part III Source: Practical Gastroenterology. 16(10): 20, 23-26, 28. November/December 1992. Summary: This article reprints part of an edited transcript of a videotape conference on irritable bowel syndrome (IBS) sponsored by Schwarz Pharma, that took place in Chicago in June 1992. Topics include dietary recommendations for patients with IBS; the role of dietary habits, including the aesthetics of mealtime; the role of stress; the link between anorexia nervosa and delayed gastric emptying; psychological factors that impact the motor function of the gastrointestinal tract; the use of anticholinergic medication; other medications used to treat IBS; timing of the dosing for IBS; sublingual administration of medications; the side effect of xerostomia; the importance of tailoring drug therapy for each individual with IBS; the emotional components of IBS; the role of sedatives or tranquilizers in IBS therapy; the effect of the menstrual cycle on symptoms of IBS; and the recent advances related to IBS. 5 references.

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Review Article: Irritable Bowel Syndrome Source: Alimentary Pharmacology and Therapeutics. 11(1): 3-15. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This article reviews current knowledge on irritable bowel syndrome (IBS), the most common disease diagnosed by gastroenterologists and one that affects about 20 percent of all people at any one time. IBS can be diagnosed positively on the basis of an established series of criteria and limited exclusion of organic disease. Symptoms

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fluctuate, and the overall prevalence rate is relatively constant in Western communities. Ten percent of patients present to their physicians. The illness has a large economic impact on health care utilization and absenteeism. IBS is a biopsychosocial disorder in which three major mechanisms interact: psychosocial factors, altered motility, and or sensory function of the intestine. Management of patients is based on positive diagnosis of the symptom complex, limited exclusion of underlying organic disease, and institution of a therapeutic trial. If patient symptoms are intractable, further investigations are needed to exclude significant motility or other disorders. Symptomatic treatment includes fiber for constipation, loperamide for diarrhea, and low-dose antidepressants or infrequent use of antispasmodics for pain. The authors note that new pharmacological agents, psychotherapy, and hypnotherapy are being evaluated for their use in treating IBS. 5 figures. 6 tables. 109 references. (AA-M). •

Evolving Concepts in Irritable Bowel Syndrome Source: Current Opinion in Gastroenterology. 15(1): 16-21. January 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: This article reviews recent research in irritable bowel syndrome (IBS). The authors note that converging evidence from investigations of the peripheral and central aspects of bidirectional brain gut interactions is beginning to shape a pathophysiological model of IBS and related functional gastrointestinal (GI) disorders. This neurobiological model includes alterations in autonomic, neuroendocrine, and pain modulatory mechanisms. The frequent association of IBS and other functional GI disorders with comorbid affective disorders and the temporal association of symptom exacerbation with psychosocial or physical stressors are consistent with alterations in the neurobiological mechanisms underlying the central stress response. The author discusses work in the area of alterations in central nervous system responses of the brain, neuroendocrine responses, autonomic dysfunction, and altered viscerosomatic sensitivity; peripheral modulators of visceral sensitivity; symptom based diagnosis; and affective disorders and psychosocial stressors. Depression and anxiety are the most common comorbid affective disorders in IBS. Classification of functional disorders according to these evolving biological markers holds the promise of a rational treatment design for subgroups of patients in the future. Renewed interest in drug development for IBS treatment has resulted in the development of diagnostic instruments for assessing the impact of symptoms on quality of life and in the development of compounds (drugs) undergoing clinical evaluation. 53 references (16 annotated).

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Psychologic Considerations in the Irritable Bowel Syndrome Source: Gastroenterology Clinics of North America. 20(2): 249-267. June 1991. Summary: This article reviews recent studies regarding the psychological considerations in the irritable bowel syndrome (IBS). Topics covered include the self-selection hypothesis; diagnostic criteria; the psychologic symptoms and personality traits associated with IBS; learned illness behavior; the role of psychologic stress; psychologic treatment of IBS, including education and reassurance, managing fears and misconceptions, and scheduling return appointments; the use of antidepressant medications; and the role of psychotherapy, including behavior therapy and hypnosis. The authors conclude that psychologically-oriented treatments have a role in the management of IBS, even in patients who do not have a psychiatric disorder. 5 figures. 1 table. 51 references.

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Irritable Bowel Syndrome: A Continuing Dilemma Source: Gastroenterology Clinics of North America. 20(2): 363-367. June 1991. Summary: This article summarizes some of the dilemmas surrounding the diagnosis and treatment of the irritable bowel syndrome (IBS). The authors discuss the classification of IBS; the diagnostic challenge of demonstrating absence of organic disease; and therapeutic dilemmas including dietary adjustments, drug therapy, and limiting the diagnostic tests performed. The article serves as a concluding summary to a series of articles in this issue devoted to IBS. 34 references.

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OTC Therapy of the Irritable Bowel Syndrome Source: U.S. Pharmacist. 15(8): 43-48. August 1990. Summary: This article was written to help pharmacists understand irritable bowel syndrome (IBS). The author notes that although the exact cause of IBS is still unknown, the symptoms may be treated by psychotherapy, changes in diet, and drug therapy. Possible causes of IBS are discussed, including food, drugs, dysentery, and stress. The use of fiber, simethicone, and/or lactase replacement as methods of treatment are discussed. Two sidebars present patient information on the proper use of over-thecounter fiber supplements and relieving IBS. References are available on request. 1 table.

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Questions and Answers: Food Allergy and Irritable Bowel Syndrome; Elective Appendectomy During Abdominal Surgery Source: JAMA. Journal of American Medical Association. 265(13): 1736, 1738. April 3, 1991. Summary: This brief article, one of a regular series of questions and answers, addresses two issues of interest to digestive diseases professionals. The first exchange discusses the possible role of food allergy in triggering or exacerbating irritable bowel syndrome (IBS). The responding author discusses the difference between food allergy and IBS, mentions research support for this hypothesis, and concludes that food allergy as a contributing factor in the pathogenesis of IBS is valid. The second exchange involves elective appendectomy during abdominal surgery. The responding author notes that there is little, if any, morbidity and that there is apparent benefit gained from incidental appendectomies, provided certain contraindications are taken into account. 7 references.

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Consensus Report: Clinical Perspectives, Mechanisms, Diagnosis and Management of Irritable Bowel Syndrome Source: Alimentary Pharmacology and Therapeutics. 16(8): 1407-1430. August 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This consensus document reviews the current status of the epidemiology, social impact, patient quality of life, pathophysiology, diagnosis, and treatment of irritable bowel syndrome (IBS). Current evidence suggests that two major mechanisms may interact in IBS: altered gastrointestinal motility and increased sensitivity of the intestine. However, other factors, such as psychosocial factors, intake of food, and prior infection, may contribute to its development. Management of patients is based on a positive diagnosis of the symptom complex, careful history and physical examination to exclude risk factors for organic disease, and, if indicated, investigations to exclude other

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disorders. Treatment choices include dietary fiber for constipation, opioid agents for diarrhea, and low-dose antidepressants or infrequent use of antispasmodics for pain, although the evidence basis for efficacy is limited or in some cases absent. Psychotherapy and hypnotherapy are the subject of ongoing study. Treatment should be tailored to patient needs and fears. Patient and physician education, early identification of psychosocial issues, and better therapies are important strategies to reduce the suffering and societal cost of IBS. 2 figures. 9 tables. 236 references. •

'It's Not All in Your Head': Irritable Bowel Syndrome Source: AJN. American Journal of Nursing. 101(1): 26-34. January 2001. Contact: Available from Lippincott Williams and Wilkins. AJN, P.O. Box 50480, Boulder, CO 80322-0480. (800) 627-0484 or (303) 604-1464. Summary: This continuing education article reviews the nursing care for patients with irritable bowel syndrome (IBS). The authors note that it is now believed that IBS has a basis in visceral hypersensitivity (of the bowel wall) and abnormal gut motor function, possibly caused by anomalies in the gut brain connection. The syndrome is neither life threatening nor associated with the development of gastrointestinal diseases such as cancer, but IBS accounts for a significant number of medical visits and prescribed medications, as well as lost work time and reduced productivity. The syndrome tends to manifest with either diarrhea or constipation or with an alternating pattern of the two. Other common symptoms include mucus in the stool, a sensation of incomplete evacuation, looser or more frequent stools with pain, and relief of abdominal pain after defecation. It has been postulated that there are differences related to sex in motility patterns, symptom and psychological profiles, pain sensitivity, and access to health care. No one factor appears to be responsible for the symptoms in all patients with IBS. Diet, stressful events, and psychological distress may also exacerbate symptoms in vulnerable patients. Diagnosis of IBS occurs by exclusion; there is no biologic marker. Therapy usually focuses on the patient's predominant symptoms and can include patient education and reassurance, nonpharmacologic interventions, and pharmacologic (drug) interventions. One sidebar explores the connection between emotional (sexual) abuse and IBS, notably assessing the effect of self blame and self silencing. A posttest for receiving continuing education credits is appended to the article. 3 figures. 1 table. 50 references.

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Treatment of Irritable Bowel Syndrome: New Approaches for a New Century Source: Practical Gastroenterology. 25(8): 13-14. August 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: This editorial serves as an introduction to a series of articles on irritable bowel syndrome (IBS). The authors note that major events have occurred in the last five years that demonstrate the role of heightened sensation to visceral pain in patients with IBS. This work has been followed by a rapidly enlarging body of knowledge using PET scanning and functional MRI imaging to detect alterations in brain activation in IBS patients. The authors emphasize that IBS does not occur in a biological vacuum, i.e., patients who seek treatment for IBS are more psychologically disturbed than patients with IBS who do not choose to seek medical care, and patients with functional GI disorders are more likely to have suffered physical or sexual abuse than patients with structurally originated GI conditions. It has become clear that gender, psychosocial trauma, concomitant psychiatric disorders, and a patient's health beliefs all can influence

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the acceptance of, adherence to, and improvement on a treatment regimen for IBS. The development of psychotherapeutic approaches, improvements in our understanding of the impact of gender and family history on treatment response, and the importance of screening for psychological disorders and psychosocial stress are all now recognized as key elements of optimal treatment. The series of articles (published in the same journal issue) reviews recent developments in the treatment of IBS using serotonergically active agents, antidepressants and antispasmodics, as well as the psychosocial dimensions that have an impact on optimal care of patients with IBS. 4 references. •

Irritable Bowel Syndrome: Simple Measures Often Relieve Symptoms Source: Mayo Clinic Health Letter. 10(12): 1-3. December 1992. Summary: This patient education article provides basic information about irritable bowel syndrome (IBS). Written in a question-and-answer format, the article covers topics including a definition of IBS; typical symptoms; and treatment options, including diet therapy and drug therapy. The author concludes that, with help from a physician and/or dietitian, patients can adopt diet and lifestyle changes that can help keep symptoms in check, usually without medication. 1 figure.

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Management of Irritable Bowel Syndrome Source: Journal of Gastroenterology and Hepatology. Volume 8: 287-293. 1993. Summary: This review article discusses recent advances in the understanding of irritable bowel syndrome (IBS) that may help the clinician design a more effective management plan. Topics include the symptom complexes that constitute IBS; the objective measurement of patient symptoms; specific intestinal motor abnormalities that may exist in patients with IBS; abnormalities in visceral perception in IBS; the role of behavioral factors in IBS; the initial patient approach and management of mild to moderate symptoms; the role of dietary manipulation, explanation and reassurance, medications, and behavioral therapy; managing patients in whom symptoms are severe and intractable; and priorities for future work in this area. 3 figures. 2 tables. 10 references.

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Review Article: Clinical Evidence to Support Current Therapies of Irritable Bowel Syndrome Source: Alimentary Pharmacology and Therapeutics. 13(Supplement 2): 48-53. May 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This review article summarizes the clinical evidence to support current therapies in irritable bowel syndrome (IBS). In patients with constipation predominant IBS, fiber is indicated at a dose of at least 12 grams per day. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhea predominant IBS; loperamide may also aid continence by enhancing resting anal tone. In general, smooth muscle relaxants are best used sparingly, on an as needed basis, since their overall efficacy is unclear. Psychotropic agents are important in relieving depression and are of proven benefit for pain and diarrhea in patients with depression associated with IBS. Further trials with selective serotonic reuptake inhibitors (SRRIs) are underway. Psychological treatments, including hypnotherapy are less widely available but may play an

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important role in pain relief. The author concludes that current therapies targeted on the predominant symptoms in IBS are moderately successful. However, therapies are needed to more effectively relieve this syndrome, not just symptoms. 1 figure. 3 tables. 60 references. •

Meta-Analysis of Smooth Muscle Relaxants in the Treatment of Irritable Bowel Syndrome Source: Alimentary Pharmacology and Therapeutics. 15(3): 355-361. March 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This review article updates previous overviews of placebo controlled double blind trials assessing the efficacy and tolerance of smooth muscle relaxants used to treat irritable bowel syndrome (IBS). A total of 23 randomized clinical trials were selected for meta analyses of their efficacy and tolerance. Six drugs were analyzed: cimetropium bromide (five trials), hyoscine butyl bromide (three trials), mebeverine (five trials), otilium bromide (four trials), pinaverium bromide (two trials), and trimebutine (four trials). The total number of patients included was 1,888, of which 945 received an active drug and 943 a placebo. The mean percentage of patients with global improvement was 38 percent in the placebo group (n = 925) and 56 percent in the myorelaxant group (n = 927). The percentage of patients with pain improvement was 41 percent in the placebo group (n = 568) and 53 percent in the myorelaxant group (n = 567). There was no significant difference for adverse events. The authors conclude that myorelaxants are superior to placebo in the management of IBS. These drugs showed significant efficacy on the global assessment despite a high placebo effect (38 percent global improvement), with a range of difference from 31 percent for cimetropium to 11 percent for hyoscin. The efficacy was also significant and in the same range for pain relief, as well as for abdominal distension relief, although lower. There was no significant difference for transit abnormalities, diarrhea, or constipation. 4 figures. 1 table. 37 references.

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Characteristics of Patients with Irritable Bowel Syndrome Recruited from Three Sources: Implications for Clinical Trials Source: Alimentary Pharmacology and Therapeutics. 15(7): 959-964. July 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Variation in the characteristics of irritable bowel syndrome (IBS) patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results. This article reports on a study undertaken to describe and compare the characteristics of three different groups of IBS patients recruited into a 'mock clinical trial.' The authors enrolled 245 irritable bowel syndrome patients from three sources: 121 patients from British primary practitioners; 72 patients from California newspaper advertisements; and 52 from a California gastroenterologist's practice. The authors obtained demographic, clinical, and Hospital Anxiety and Depression (HAD) Scale data for each patient. Most patients were young to middle aged women; in all three groups, the majority reported symptoms for longer than 5 years. Subject characteristics varied among the groups. Typically, primary care patients were anxious, smokers, and daily alcohol drinkers who had sought care recently for IBS and had tried antispasmodic drugs. Their symptoms were intermediate in severity between

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those of the other two groups. Advertisement subjects were the oldest, most highly educated, most often depressed, and were least likely to have sought care recently for symptoms, which were almost uniformly only moderate in severity. Gastroenterologist patients tended to be anxious and had nearly all sought care recently for symptoms, which were the most severe and most likely to include all three pain related Rome I criteria. The authors conclude that recruitment methodology affects important characteristics of an IBS study group. Trial reports should describe as completely as possible the recruitment method and the relevant subject characteristics to aid clinicians in deciding how the results might apply to their patients. 1 table. 26 references. •

Irritable Bowel Syndrome in the Elderly Source: Gastroenterology Clinics of North America. 20(2): 369-390. June 1991. Summary: Very little has been written about irritable bowel syndrome (IBS) in the elderly, although epidemiologic studies suggest that it is a common problem in this age group. This article discusses the definition, clinical features, epidemiology, causes and pathogenesis, diagnosis and differential diagnosis, treatment, and prognosis of IBS in the elderly. The authors stress that more study is needed, particularly in the areas of pathophysiology of IBS in the aged, investigation of personality, psychiatric symptomatology, mental state, and functional status in the elderly with IBS, and in documenting the prevalence and incidence of this phenomenon. 6 tables. 125 references.

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Menstrual Cycle and Its Effect on Inflammatory Bowel Disease and Irritable Bowel Syndrome: A Prevalence Study Source: American Journal of Gastroenterology. 93(10): 1867-1872. October 1998. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-6423 or (410) 528-8555. Summary: Women with bowel disease commonly report that their symptoms worsen in relation to their menstrual cycle. This article reports on a study undertaken to determine the nature of gastrointestinal (GI) symptoms correlating with the menstrual cycle in women with inflammatory bowel disease and irritable bowel syndrome (IBS). This retrospective study involved 49 women with ulcerative colitis, 49 women with Crohn's disease (CD), 46 women with IBS, and 90 healthy community controls. Participants were interviewed using a questionnaire that included information on general health, medication history, pregnancy, and premenstrual and menstrual symptoms. Premenstrual symptoms were reported by 93 percent of all women but statistically more often by patients with CD. Patients with CD were also more likely to report increased GI symptoms during menstruation; diarrhea was the symptom reported most often. All disease groups had a cyclical pattern to their bowel habits significantly more than controls. Cyclical symptoms included diarrhea, abdominal pain, and constipation. The authors conclude that the prevalence of menstruation related symptoms is high and appears to affect bowel patterns. The physiological and clinical effects of the menstrual cycle should be taken into consideration when assessing disease activity. 3 figures. 2 tables. 13 references. (AA-M).

Federally Funded Research on Irritable Bowel Syndrome The U.S. Government supports a variety of research studies relating to irritable bowel syndrome. These studies are tracked by the Office of Extramural Research at the National

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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 irritable bowel syndrome. 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 irritable bowel syndrome. The following is typical of the type of information found when searching the CRISP database for irritable bowel syndrome: •

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

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

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Project Title: A SYNDROMEN

NOVEL

DIAGNOSTIC

TEST

FOR

IRRITABLE

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Principal Investigator & Institution: Wagner, David A.; Metabolic Solutions, Inc. 460 Amherst St Nashua, Nh 03063 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Irritable Bowel Syndrome (IBS) is a life altering disorder of the intestines that effects approximately 20 percent of the general population. There is no single diagnostic test for positive confirmation of IBS. Physicians arrive at an lBS diagnosis following a protocol that uses standard endoscopic tests to exclude structural or biochemical abnormalities, a physical examination and a symptom questionnaire. This inefficient process leads to an enormous use of healthcare resources estimated at 3.5 million office visits and 2.2 million prescriptions at a direct and indirect cost of $29 billion annually. Our objective is to develop an easy to use, low cost breath test to diagnosis lBS. The test developed by Metabolic Solutions (MSI) is based on the principle that lBS patients malabsorb fructose. In preliminary studies MSI has demonstrated a novel technology using a carbon 13 tracer and unlabeled fructose to identify individuals with lBS by whether or not they can absorb the administered fructose. This is the first test to assay fructose malabsorption directly from the small intestine and correlate it to the diagnosis of LBS. The proposed test will significantly reduce national health care expenditures because proper diagnosis will lead to fewer office visits, more prudent use of drugs and better general health and well-being for a large number of Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A NURSING STUDY OF GUT FUNCTION IN MENSTRUATING WOMEN Principal Investigator & Institution: Heitkemper, Margaret M.; Professor & Director; Biobehavioral Nursing and Health Systems; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 15-SEP-1984; Project End 29-FEB-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A TWIN STUDY OF CHRONIC FATIGUE SYNDROME IN SWEDEN Principal Investigator & Institution: Pedersen, Nancy L.; Karolinska Institute Tomtebodavagen 11F Stockholm, Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Despite considerable research, fundamental questions about CFS remain at best partially answered. These questions include its definition, validity, the degree to which it results from genetic versus environmental factors, the nature of the substantial comorbidity observed with other conditions, and the basis of the female preponderance. The overarching aim of this project is to shed light on a number of basic questions about CFS via a large, population-based classical twin study. First, we will collect data on approximately 32,000 adults aged 42-65 years (13,000 complete twin pairs) who are members of the population- based Swedish Twin Registry for persistent fatigue, several overlapping conditions (fibromyalgia, irritable bowel syndrome, tension headache, allergy/eczema, generalized anxiety disorder, and major depression), and a detailed medical history. Second, the medical records of all twins who appear to have CFS-like illness and a subset of those with "CFS-explained" will be requested via an efficient

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national retrieval system. Following expert review, these individuals will be classified in regard to the CDC CFS criteria. Obtaining these unique data will allow us to address a set of critical questions regarding CFS. First, we will estimate the prevalence of CFS and its common comorbidities (fibromyalgia, irritable bowel syndrome, tension headache, allergy/eczema, generalized anxiety disorder, and major depression) in one of the largest samples yet studied. Second, we will use a variety of multivariate techniques to derive an empirical typology of prolonged fatigue and to assess how this typology compares to the CFS definition. Third, we will quantify the genetic and environmental sources of variation for CFS and its comorbid conditions. Fourth, critically, we will examine the influence of gender on these sources of variation. Finally, we will analyze the patterns of comorbidity between CFS and fibromyalgia, irritable bowel syndrome, tension headache, allergy/eczema, generalized anxiety disorder, and major depression using multivariate twin analyses and thereby to estimate the extent of overlap between the shared and unique genetic and environmental sources of variation. In concert with other twin studies being conducted by the investigators and their collaborators, we hope to hasten progress in understanding the etiology of CFS by parallel studies in multiple populations. The current proposal has several unique aims and represents a costeffective means to extend this work in an epidemiological sample that is arguably the best twin registry in the world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALPHA-2 ADRENERGIC CONTROL OF COLONIC FUNCTION IN IBS Principal Investigator & Institution: Camilleri, Michael L.; Professor of Medicine and Physiology; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001 Summary: Our hypotheses are that alpha-2 adrenergic mechanisms modulate colonic sensation in health and in patients with irritable bowel syndrome associated with increased frequency of bowel movements and urgency; and that lower doses of the alpha-2 agonist, clonidine, are required to reduce colonic sensation in IBS compared to health; these antinociceptive effects are achieved without altering colonic compliance or motor function in patients with irritable bowel syndrome. The specific aims of the study are to study the alpha-2 adrenergic modulation of colonic compliance, tone and sensation in healthy human volunteers; to study the alpha-2 adrenergic modulation of gastrointestinal and colonic transit time in healthy human volunteers; and to study the alpha-2 adrenergic modulation of colonic transit, tone, compliance, and sensation in patients with well-characterized autonomic function who have irritable bowel syndrome associated with increased frequency of bowel movements and/or urgency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUTONOMIC CONTROL OF BODY WEIGHT AND FEEDING Principal Investigator & Institution: Powley, Terry L.; Distinguished Professor; Psychological Sciences; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2002; Project Start 01-JAN-1980; Project End 30-NOV-2006 Summary: The proposed project continues a programmatic investigation of the neural mechanisms of feeding and body weight regulation. The long- range goal of the project is a comprehensive functional neuroanatomy of energy homeostasis. For the immediate future, the proposed experiments concentrate on a series of structure-function analyses of the vagus nerve. Extensive evidence has established that the vagus, the Xth cranial

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nerve, is critically involved in controlling ingestion and body energy regulation. Presently, however, continued progress in analyzing vagal mechanisms involved in ingestive behavior and physiology is seriously limited by a lack of fundamental structural information about the vagal projections to the gastrointestinal tract. Hence, the immediate goal of the project is the completion of a series of promising analyses that are characterizing the morphological types, regional topographies and functions of vagal projections linking the brain and GI tract. The first aim is to complete a series of experiments on vagal afferent, or sensory, endings in the alimentary canal. This aim includes characterizing structurally and then classifying afferent terminals in the mucosa and submucosa of the GI tract. It also includes developing topographic maps of the concentrations of these chemo-, osmo-, thermo- and mechano- receptors throughout the GI tract. The second aim is to characterize the patterns and timetables of regeneration of each of the different types of vagal projections to the GI tract. These experiments will also correlate the newly identified patterns of structural plasticity with recovery of function. The third aim is to extend our structure-function analyses by screening mutant mice with selective afferent vagal ablations for potential alterations in feeding behavior. Inventories of the different vagal endings, surveys of their terminal distributions, and characterizations of the plasticity in these vagal projections produced by damage or mutation will yield information needed to design, guide and interpret both experimental and surgical manipulations of the autonomic nervous system and GI tract. The program outlined also will extend our understanding of major neural mechanisms implicated in metabolic and digestive diseases including obesity, eating disorders, anorexia, disorders of swallowing, diabetes, vagal dysfunction, autonomic neuropathies, visceral pain, irritable bowel syndrome, and peptic ulcers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOMECHANICS OF ESOPHAGEAL WALL AND VISCERAL SENSATION Principal Investigator & Institution: Mittal, Ravinder K.; Professor of Medicine; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, Ca 92161 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): The biomechanical properties of the esophagus have relevance to its motor and sensory function. These properties have been studied in the animals and humans by several investigators using various techniques. However, there are limitations with each of these techniques. We have developed a novel system of balloon ultrasonography that measures esophageal pressure, radius and wall thickness simultaneously, in vivo, in humans. Our technique, therefore, allows accurate measurement of the wall stress, strain and elastic modulus (wall rigidity) on a continuous time basis. Our preliminary data show that in normal subjects there is a close temporal correlation between increase in intraluminal pressure and esophageal wall thickness, which allows the esophagus to maintain a low wall stress. Patients with motility disorders of the esophagus have a thicker esophageal muscularis propria compared to normal subjects. We hypothesize that difference in the biomechanical properties of the esophageal wall between normal subjects and patients is the reason for impaired esophageal transport and dysphagia in patients with motility disorders of the esophagus. The current understanding is that hypersensitivity of the esophagus is the cause of esophageal pain. Patients with presumed esophageal pain respond to distension of the esophagus at lower balloon volumes than normal subjects. The site of esophageal hypersensitivity may be at either the peripheral (esophageal wall) or at the central level (CNS). The latter is currently the favored site. The differences in the

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Irritable Bowel Syndrome

biomechanical properties of the esophageal wall in patients and normal subjects may result in different wall stress and strain in response to the same volume of distension. We hypothesize that differences in the biomechanical properties of the esophagus may be the reason for a hypersensitive esophagus. The specific aims of our studies are: 1: In vitro validation of the novel technique of balloon-ultrasonography. 2: To determine biomechanical properties of the esophagus in normal human subjects using balloon ultrasonography and to determine the relationship between esophageal pain and its biomechanical properties. 3: To define the abnormalities of muscularis propria thickness in patients with primary motility disorders of the esophagus. 4: To determine the biomechanical properties of the esophageal wall in patients with a normal and thick muscularis propria and its relationship to esophageal hypersensitivity. 5: To study biomechanics of the esophageal wall in patients with esophageal dysphagia. We believe that our observations have important implications in understanding the mechanisms of esophageal motor and sensory function in healthy and diseased states. Furthermore, the principles discussed in the esophagus may be applicable to the understanding of visceral hypersensitivity seen in irritable bowel syndrome and other functional disorders of the GI tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALGESIA

BRAIN

IMAGING

AND

PAIN:

ANALYSIS

OF

PLACEBO

Principal Investigator & Institution: Robinson, Michael; Clinical & Health Psychology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 31-DEC-2006 Summary: (provided by applicant): This project is designed to investigate the neural mechanisms of placebo analgesia. An innovative placebo protocol that assesses the placebo response to both visceral and cutaneous pain stimulation will be employed. Functional Magnetic Resonance Imaging (fMRI) will enable the characterization of brain mechanisms involved in placebo analgesia in a clinical population which experiences visceral pain as part of their clinical syndrome. This project will capitalize on previous work with Irritable Bowel Syndrome (IBS) patients where differential brain activation was demonstrated to visceral and cutaneous pain stimuli. In this same population a powerful and reliable placebo response to specific expectancy response sets has been demonstrated. The proposed project will combine these protocols to obtain brain images of IBS subject during natural history, placebo, and active agent (rectal lidocaine) conditions. It is anticipated that results will show that the placebo response will selectively activate specific brain regions. Neural activity (as measured by rCBF) will be greater in natural history conditions as compared to placebo conditions in the following brain regions: - lateral and/or medial thalamus, somatosensory areas 1 and 2, insular cortex, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and prefrontal cortex. Furthermore, placebo mechanisms that operate primarily through attenuation of nociceptive signals at lower nervous system levels (spinal cord) will be evidenced by decreased thalamic, somatosensory, ACC, and PCC activation. Previous research indicates that expectancy and desire for pain relief will significantly predict the pain reduction from placebo. It is anticipated that these measures will also be associated with the above described brain activation patterns. By comparing the placebo conditions to the rectal lidocaine condition, brain and central nervous system related mechanisms versus peripheral (receptor site) related mechanisms will be differentiated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BRAIN/PELVIC VISCERA INTERACTIONS IN PSYCHIATRIC DISEASE Principal Investigator & Institution: Valentino, Rita J.; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 05-SEP-1998; Project End 31-AUG-2003 Summary: A striking feature of mood and anxiety disorders is their frequent coexistence with functional bowel disorders, such as irritable bowel syndrome. Conversely, psychiatric symptoms are prevalent in subjects diagnosed with functional bowel disorders, which occur in 10-20% of adults. These clinical observations implicate neural substrates linking the brain and gastrointestinal tract in pathology that is prevalent in the adult population. In the current application, a specific circuit linking the forebrain and gastrointestinal tract is proposed. It is proposed that Barrington's nucleus, via divergent projections to the brain noradrenergic nucleus, locus coeruleus (LC) and autonomic parasympathetic nuclei, is in a position to co-regulate brain noradrenergic activity and autonomic parasympathetic activity and thereby coordinate forebrain activity with gastrointestinal function. The proposed aims will provide anatomic and functional evidence for this hypothesis: The specific aims are: (1) Identify regions of the gastrointestinal tract that are linked to the LC via Barrington's nucleus. Transsynaptic tracing (using pseudorabies virus) from the colon, cecum and bladder will be combined with retrograde tract tracing from the LC to determine whether Barrington's LCprojecting neurons also project to preganglionic neurons innervating these organs; (2) Characterize the physiological impact of Barrington's sacral spinal-projections on colon function. Barrington's nucleus has been studied only with regard to its role in micturition. Its projections to the sacral parasympathetic nucleus suggest that it also regulates distal colon function. This hypothesis will be tested by characterizing the effects of selective chemical stimulation of Barrington's nucleus on colonic intraluminal pressure: (3) Determine the role of Barrington's LC-projections in arousal elicited by colon or bladder distension. Colon and bladder distension increase LC discharge and produce arousal as indicated by forebrain electroencephalographic (EEG) activation. The hypothesis that forebrain arousal elicited by colon or bladder distension is mediated by Barrington's projections to the LC will be determined using micro infusion of drugs to selectively inactivate the LC or Barrington's nucleus. Together, these AIMS will begin to elucidate the anatomy and functions of a novel circuit that it is in a position to coordinate forebrain and gastrointestinal activity; a circuit that could play a role in the prevalent disorders that are characterized by a coexistence of psychiatric and gastrointestinal symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE Principal Investigator & Institution: Sandler, Robert S.; Professor of Medicine; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-DEC-1994; Project End 30-NOV-2004 Summary: (Taken from the application) Members of the Center for Gastrointestinal Biology and Disease (CGIBD) are basic and clinical scientists from diverse disciplines dedicated to advancing our understanding of gastrointestinal biology, physiology and epidemiology with a special emphasis on inflammatory bowel diseases. Research on mechanisms responsible for gastrointestinal diseases can be grouped into four major categories: inflammation, fibrogenesis, proliferation and epidemiology/clinical research.

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Irritable Bowel Syndrome

The goal of the center is to promote and enhance multidisciplinary digestive disease research. The center achieves this goal through: 1) core facilities that provide training, technical support, laboratory animals, assays, imaging and purified cell populations; 2) a pilot feasibility program that offers startup funds to junior investigators, or to established digestive disease research. The center achieves this goal through: 1) core facilities that provide training, technical support, laboratory animals, assays, imaging and purified cell populations; 2) a pilot feasibility program that offers startup funds to junior investigators, or to established investigators who wish to pursue a new research direction; 3) a scientific enrichment program consisting of seminars, symposia and workshops to improve the intellectual climate for digestive disease research and to promote cooperation, collaboration and communication among involved personnel; 4) a professional development and training program that fosters the development of junior faculty. To support the research of members, the center proposes the following cores: 1) Biostatistics and Data Management; 2) Immunotechnologies 3) Advanced Cell Technologies and Tissue Engineering (cell culture and multiparametric cell sorting); 4) Molecular Imaging (confocal microscopy, in-situ hybridization, histology); 5) Gene Delivery; and 6) Gnotobiotic Animal. Gastrointestinal diseases and their complications have a significant health and economic impact. Research by members of this center has led to fundamental breakthroughs in our understanding of mechanisms responsible for inflammatory bowel diseases, cirrhosis, irritable bowel syndrome, and colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CENTRAL HYPERSENSITIVITY

MECHANISMS

MODULATING

VISCERAL

Principal Investigator & Institution: Greenwood-Van Meerveld, Beverly; Scientific Director; Oklahoma Foundation for Digestive Res Digestive Research Oklahoma City, Ok 73104 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 28-FEB-2003 Summary: Irritable bowel syndrome (IBS) symptoms are due in part to alterations in visceral sensation. IBS symptoms are frequently exacerbated by stress and anxiety, which suggests a link between cognitive and peripheral autonomic activity. The amygdala has been implicated as a key limbic structure involved in anxiety and activation of the hypothalamic-pituitary-adrenocortical axis. It has been demonstrated that administration of glucocorticoids in the area of the amygdala increases anxiety in rats. Furthermore, rats genetically predisposed to heightened levels of anxiety display a hypersensitive response to colonic distention. The PI hypothesizes that manipulation of amygdala function by glucocorticoids induces colonic hypersensitivity through modulation of spinal neuronal activity. The PI proposes to modulate anxiety by manipulating amygdala function directly with corticosterone and specific glucocorticoid antagonists to determine mechanisms by which the CNS regulates visceral sensitivity. Visceromotor reflexes in response to colorectal distention will be used to determine visceral hypersensitivity in rats with normal and "hypersensitive" colons. It is proposed that chronic stress resulting in elevated glucocorticoid levels could, through the amygdala, modulate the function of critical spinal neurons involved in the colonic stimuli. To further explore the mechanisms involved the PI will modulate amygdala function with glucocorticoids and its effect on spinal cord neuronal activity. Recordings will be made from rat lumbosacral spinal nerves in response to colonic distention following treatment with corticosterone or specific antagonists delivered to the amygdala. This R21 proposal will develop collaborations among scientists in GI neurophysiology, pharmacology, and neuroendocrinology.

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

Project Title: MOTILITY

CHOLECYSTOKININ--ROLE

IN

POSTPRANDIAL

GASTRIC

Principal Investigator & Institution: Raybould, Helen E.; Associate Professor; Clinical Research Center; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 01-AUG-1989; Project End 31-AUG-2004 Summary: Nutrients in the intestinal lumen initiate changes in motor function of the gastrointestinal tract. Intestinal lipid acts via a cholecystokinin A receptor- (CC.-AR) and a vagal afferent-dependent pathway. The hypothesis to be tested is that intestinal lipidinduced inhibition of gastric motility is dependent on absorption of lipid by enterocytes, formation and release of chylomicrons and apolipoprotein A-IV (apoA-IV), release of CCK. by apo A-IV and CCK acting on CCK-ARs on intestinal afferent nerve terminals. To test this hypothesis, studies are proposed to determine that: (1) inhibition of gastric emptying by lipid in the intestinal lumen depends on chylomicron formation and release of apo A-IV; (2) release of CCK in response to lipid is dependent on chylomicron formation and release of ap A-IV; (3) activation of vagal afferents in response to intestinal lipid is dependent on release of apo A-IV and CCK-AR activation and (4) to demonstrate the expression of CCK-AR on neuronal elements in the stomach and duodenum and their functional regulation by CCK. The role of chylomicron formation in lipid- induced inhibition of gastric emptying or motility and release of CCK will be determined in rats using the surfactant pluronic L81. Postabsorptive chylomicron products in mesenteric lymph will be given intra-arterially to demonstrate their effectiveness to inhibit gastric motility and act via a CCK-AR- and vagal capsaicindependent pathway. The role of apo A-IV in inhibition of gastric motility and CCK release in response to lipid will be determined by in vivo immunoneutralization, removal of apo A-IV from chylous lymph by immunoprecipitation, and by exogenous administration of apo A-I. Lipid-induced inhibition of gastric emptying and release of CCK will be measured in apo A-IV over-expressing and apo A-IV knockout mice. CCK secretion from STC-1;cells will be measured in vitro to determine that apo A-IV acts direct on endocrine cells. Intestinal vagal afferent fiber discharge will be measured in response to intestinal perfusion of lipid and exogenous administration of apo A- IV acts directly on endocrine cells. Intestinal vagal afferent fiber discharge will be measured in response to intestinal perfusion of lipid and exogenous administration of apo A-IV and determine that both of these responses are CCK-AR- dependent using the CCK-AR antagonist devazepide. A direct effect of Cck on vagal afferents innervating the gastroduodenum will be determined by measuring calcium fluxes in response to CCK in nodose neurons in vitro. The cellular sites of expression and origins of Cck-ARs will be determined in immunohistochemical studies using antisera raised to different regions of the rat CCK-AR in tissue from intact, extrinsically denervated or capsaicin treated rats The co- localization of CCK-AR with other enteric neuropeptides, and with neuronal and endocrine CCK will be determined in double labeling experiments. The functional regulation of Cck- Ars in the stomach and duodenum will by investigated using exogenous and endogenous CCK and devazepide. These studies address sensory transduction in the gastrointestinal tract which is important in the regulation of normal digestive function. There is evidence that sensory function of the intestine is altered in pathological conditions such as inflammatory bowel disease, irritable bowel syndrome and obesity. A greater understanding of these sensory mechanisms will help in understanding the pathophysiology of these diseases.

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Irritable Bowel Syndrome

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

Project Title: COGNITIVE APPROACHES TO MODIFYING HUMAN PAIN PERCEPTION Principal Investigator & Institution: Bushnell, M. Catherine.; Professor; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The vast majority of analgesic research has focused on pharmacological agents, addressing particularly the peripheral and spinal cord mechanisms of opioid and anti-inflammatory therapy. It is now recognized, however, that a variety of modulatory mechanisms exists in the nervous system, and more importantly, that many of these endogenous pathways can be accessed through cognitive manipulations. The proposed research investigates a number of cognitive factors that modulate pain perception, examines their interrelationships, and explores possible cerebral mechanisms underlying their action. Study 1 will test the hypothesis that emotional context influences pain perception independent of attentional factors. Psychophysical studies in normal human subjects will employ cross-modality attention tasks, hedonically charged olfactory stimuli (to modify emotional context), and noxious heat as a painful stimulus. Functional magnetic resonance imaging (fMRl) will subsequently examine cerebral activation associated with these cognitively activated pain-modulatory systems. Study 2 will test the general hypothesis that cognitive modulation of pain perception is more pronounced for visceral than for cutaneous stimuli, as suggested by clinical evidence indicating a strong influence of emotional state on chronic visceral pain, such as the pain of irritable bowel syndrome or non-cardiac chest pain. This study will address the issue experimentally, using psychophysical and fMRl testing to compare directly the influence of emotional context and/or attentional state on sensory and affective aspects of visceral and cutaneous pain perception in normal human subjects. Finally, based on recent suggestions of gender dissimilarities in endogenous pain-modulatory systems, we will examine, in the above studies, sexrelated differences in the modulatory influences of emotional context and attention on both the sensory and affective dimensions of pain perception. The influence of a patient's cognitive state on pain has been largely ignored in western medicine. Results of the proposed studies may help educate both physicians and patients about cognitive effects on pain and guide future development of cognitive strategies for pain control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGNITIVE THERAPY FOR IBS--OUTCOME, PROCESS & PREDICTION Principal Investigator & Institution: Blanchard, Edward B.; Distinguished Professor; Psychology; State University of New York at Albany 1400 Washington Ave Albany, Ny 12222 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: (adapted from investigator's abstract): Irritable Bowel Syndrome (IBS) is a widespread, chronic, disorder of the lower gastrointestinal tract which seems relatively refractory to standard medical care. Recent research from our laboratory strongly suggests that cognitive therapy (CT) is highly effective (70-80 percent clinically improved) in the short-term (out to 3 months post-treatment). The current application seeks to replicate and extend our previous small-scale studies by conducting a controlled clinical trial of CT vs. a self-help support group as an attention placebo

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control and symptoms monitoring wait list of 240 chronic IBS patients and follow up the treated patients for at least 12 months. To complete the project in a timely fashion a second site, University of Buffalo Medical Scholl, will be added to run half of the sample. Within this overall project 5 studies will be conducted: (a) examination of relations between stress, especially minor stressful events, and IBS symptoms; (b) controlled comparison of brief (10 sessions) CT administered in small groups to (SG) and to (sic) symptom monitoring. The latter will subsequently be treated to increase the sample sizes for studies c, d, and e; (c) identification of the processes of change within the CT treatment of IBS by examining, at various levels of analysis, the relations between changes in cognitive variables and changes in GI symptoms; (d) prospective one-year follow-up of the effect of CT and SG on IBS; (e) prediction algorithm for the results of the CT treatment of IBS from variables derived from the careful pretreatment assessment of participants; we will determine prediction schemes of end of treatment and a 3-month follow-up as well as what variables predict maintenance of symptom relief over the 12 month follow-up. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROLLED FIBROMYALGIA

FAMILY

STUDY

IN

PATIENTS

WITH

Principal Investigator & Institution: Arnold, Lesley M.; Associate Professor; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: Fibromyalgia, a chronic musculoskeletal pain disorder of unknown etiology, is a significant public health problem. Evidence from studies of phenomenology, comorbidity, family history, and pharmacologic treatment response suggest that fibromyalgia may be associated with major mood disorder, and possibly to a proposed group of conditions known as affective spectrum disorders. Prior psychiatric research has demonstrated that major mood disorder is highly familial. Family history studies provide a method by which to assess how medical disorders co-aggregate in families and, therefore may share a common risk factor or pathophysiologic mechanism. To date, few studies have explored the morbid risk of major mood disorder (and other proposed affective spectrum disorders) in probands with fibromyalgia and their first- degree relatives. All of these studies have used the family history method, which entails interviewing probands regarding their knowledge of psychiatric illness in relatives. Although most of these studies have provided important preliminary data suggesting an association between fibromyalgia and major mood disorder, this method has been demonstrated to be less sensitive in detecting illness in relatives than direct interview (the family interview method). In order to provide further evidence of a relationship between fibromyalgia and major mood disorder, we propose to study the prevalence of psychiatric and rheumatologic disorders in probands with fibromyalgia and their firstdegree relatives as compared to probands with rheumatoid arthritis and their relatives using the family interview method. In addition to assessing the degree of co-aggregation of these disorders within families, we will also study the occurrence of other conditions within the proposed group of affective spectrum disorders in relation to fibromyalgia, and the association between the severity of fibromyalgia symptoms and the presence of major mood disorder within families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--HUMAN STUDIES Principal Investigator & Institution: Jensen, Dennis M.; Professor of Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: (Adapted from the application) The mission of the Human Studies Core is to provide shared resources, personnel, services, education, and consultation to CURE investigators, trainees, and their collaborators for the study of patients with selected digestive diseases. The primary goal of this core is to facilitate collaboration, education about, and performance of GI clinical trials, human physiological studies, and health service studies in digestive diseases. The traditional focus of the core has been the investigation of peptic diseases and upper GI physiology, including secretion, motility, and hormonal regulation. This focus has been broadened to include the study of other important gastrointestinal illnesses such as complicated ulcer disease, gastroesophageal reflux disease (GERD), Barrett's epithelium, GI hemorrhage, non-ulcer dyspepsia, Helicobacter pylori infection, pre-cancer conditions (gastritis, polyposis, and ulcerative colitis), and inflammatory bowel disease. An overriding theme of the core is the study of the physiology of visceral pain which may be associated with all of these disorders. The importance of this area in GI diseases is highlighted by the impact of GI symptoms on quality of life and demand for health care services. With this in mind, the core has greatly expanded the study of neuroenteric diseases such as irritable bowel syndrome (IBS), non-ulcer dyspepsia, and non-cardiac chest pain. The specific goals of this core are to provide CURE investigators, trainees, and their collaborators with access to: (1) a quality clinical research unit for performance of GI clinical research at a low cost, (2) utilization of fully equipped endoscopy units for GI clinical and physiologic research studies, (3) laboratory services for GI secretory tests, GI motility and pH testing, and H. pylori assessments (ELISA, C-14 breath testing, and histopathology), (4) teaching of clinical research techniques and consultation about study design, data management, statistical analysis, and routine outcomes, (5) tissue and clinical data banks of patients with selected GI diseases (the largest data bases are for GI hemorrhage and functional GI disease), (6) consultation about conducting health services research including design of studies, cost assessments, quality of life instruments, effectiveness studies, and modeling cost-effectiveness studies, (7) specialized equipment for GI studies (such as equipment for ablating Barrett's epithelium or endoscopic ultrasound instruments), (8) psychophysiology and GI motility laboratories for the study of neuroenteric diseases, and (9) utilization of a brain imaging unit for the study of neuroenteric diseases. The instruments and personnel required for these services and functions are expensive, so that sharing them among various investigators in a core is cost effective and promotes collaboration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENHANCING THE PLACEBO EFFECT IN IRRITABLE BOWEL SYNDROMEN Principal Investigator & Institution: Kaptchuk, Ted J.; Director of Complementary Specialties; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-DEC-2006 Summary: (provided by applicant): This grant continues our ongoing research on how placebo effects can be enhanced and provides crucial data on the placebo effect's

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scientific validity and clinical significance. Our model uses Irritable Bowel Syndrome (IBS) to study the placebo effects elicited by different patient-practitioner contexts. In phase one, 260 patients will be randomized to a 3 week three arm RCT comparing: 1. sham needle treatment (a validated sham acupuncture placebo device) given in the context of a patient-practitioner interaction 'augmented' with positive cognitive, emotional and symbolic interactions, 2. identical sham given within a 'limited' contextual interaction, 3. a no treatment control. The primary question tested is whether the 'nonspecific' effects across the two sham device arms and the no treatment arm behave monotonically in a manner analogous to 'dose dependence' i.e. is 'augmented' arm > 'limited arm' > wait-list natural history. This trial also allows us to answer whether 1. the placebo effect in IBS can be enhanced, i.e., does an 'augmented' placebo intervention elicit a greater placebo effect than a 'limited' placebo intervention and 2. whether the 'limited' placebo intervention elicits a greater placebo effect than natural history arm with any 'non-specific' effects attendant to being in a no-treatment control. To maintain ethical norms, phase two will continue the same context, but sham acupuncture will seamlessly be switched to verum acupuncture to explore acupuncture's efficacy in IBS. In addition, a second parallel qualitative study will follow 27 additional patients (whose outcome data will be excluded from the larger study's analysis) through the same three arms; the study will use interviews to explore the relationships between patients' interpretations and understandings (what anthropologists call 'meaning') of IBS, and their responses to placebo and verum treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL BOWEL DISORDERS IN CHINESE MEDICINE Principal Investigator & Institution: Berman, Brian M.; Director; Family Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-MAR-2005 Summary: (provided by applicant): This application is for a Planning Grant for International Centers for Research on Complementary and Alternative Medicine (PICRC) in response to RFA AT-03-002. The goal of planning phase activities is to begin creation of the Functional Bowel Disorders and Traditional Chinese Medicine Research Group, with the participation of consortium members of three universities, The University of Maryland Center for Integrative Medicine, the Chinese University of Hong Kong, and the University of Illinois at Chicago Program for Collaborative Research in the Pharmaceutical Sciences. The consortium will develop a grant application for an International Center for Research on Complementary and Alternative Medicine (ICRC) to be submitted during the two-year planning phase, which will request funding to support three pilot projects related to irritable bowel syndrome and three cores: a Pharmacologic Core, a Data Management, Analysis, and Coordination Core, and an Administrative Core. The projects to be proposed will include 1) a rat model irritable bowel syndrome treatment trial using acupuncture and herbs, 2) a human pathophysiology pilot study on the effect of TCM on cerebral cortical activation and visceral sensation to rectal distension in IBS patients and non-IBS volunteers, and 3) Phase I and II clinical trials of TCM treatment in diarrhea-type IBS patients. Pilot studies in the animal model, standardization and authentication of the herbal preparation, and the techniques of human rectal distension in the functional MRI environment will be conducted in the planning phase to facilitate the projects to be proposed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Irritable Bowel Syndrome

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Project Title: GDNF IN THE ENTERIC NERVOUS SYSTEM Principal Investigator & Institution: Xia, Yun; Anesthesiology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This is a proposal for a KO8 Mentored Clinical Scientist Development Award for a physician scientist who holds an M.D. and Ph.D. in Physiology. The applicant aims to acquire the skills and conceptual knowledge necessary for conducting research on the nervous system of the digestive tract. This requires advanced training in electrophysiological methods, fluorescent immunohistochemistry and molecular biology to be obtained during the 5-year tenure of the Award. A lifelong career as a clinician scientist in an academic medical center is the applicant's goal. The proposed research is in the new and rapidly developing field of neurogastroenterology. The focus in this proposal on the enteric nervous system as a "brain-in-the-gut" addresses an important aspect of neurogastroenterology that is related to functional gastrointestinal disorders. Functional gastrointestinal disorders are believed to reflect neuropathic changes in the enteric nervous system that may be manifest as the irritable bowel syndrome (IBS), nonulcer dyspepsia or non-cardiac chest pain. The research is directed to understanding the role of glial derived neurotropic factor (GDNF) in the enteric nervous system. GDNF came to scientific and clinical life as a promising treatment to reverse neuronal degenerative changes in the brain that lead to Parkinson's disease. GDNF is a protective factor for neurons in the brain and peripheral nervous system. Mutations in the GDNF gene leads to Hirschsprung's disease in animals and humans. Parkinsonian patients in recombinant GDNF therapy trials experienced IBS-like diarrhea and cramping abdominal pain. Human trials showed evidence of a prokinetic action on gastrointestinal transit. The general scientific aim of the proposed work is to understand how GDNF works in the "brain-in-the-gut" to alter motility and secretory functions. The investigative work is based on results of pilot/feasibility studies that show significant actions of applied GDNF on both neuronal excitability and neurotransmission. Experimental protocols are designed to: 1) determine the action of GDNF on electrical and synaptic behavior of neurons in the enteric nervous system; 2) identify the morphological types of enteric neurons on which GDNF acts; 3) determine the localization and distribution of GDNF receptors in the enteric nervous system; 4) identify subtype/s of GDNF receptors that mediate its action on enteric neurons; 5) investigate factors that influence gene expression for the GDNF receptors in enteric neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GRADUAL EXPOSURE TREATMENT FOR IRRITABLE BOWEL SYNDROMEN Principal Investigator & Institution: Decola, Joseph P.; Psychology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-APR-2001 Summary: The most commonly used non-medical treatment for Irritable Bowel Syndrome (IBS) is a combination of traditional stress management techniques and nonspecific cognitive therapy methods. This general approach is used to treat patients with divergent target symptoms (i.e., constipation and diarrhea). A limitation of this approach is that the treatment is not derived from a clear theoretical model that identifies a specific process underlying the disorder or treatment. The present study is based on a strong theoretical model that offers specific predictions and treatment

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methods. The model assumes that hypervigilance and hypersensitivity to internal sensations in the gut are the critical perceptual mechanisms underlying IBS. These perceptual filters are the result of learning and conditioning processes and can be reversed with a cognitive-behavioral treatment that incorporates gradual exposure to internal sensations. Subject recruitment will be limited to IBS patients with diarrhea as the predominant symptom and the treatment will be implemented with a multiple baseline across subject design. The treatment will consist of several phases: education about the role of learning in the development of IBS symptoms; relaxation training; cognitive restructuring for overestimation and catastrophization errors; exposure to the feared internal sensations; and exposure to avoided situations. The goal of this treatment is to reverse the hypersensitivity and hyperviligance through gradual exposure to these stimuli. The broad objective of this research is to enhance the treatment for IBS and to test the predictions of this theoretical model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERGENERATIONAL TRANSMISSION OF ILLNESS BEHAVIOR Principal Investigator & Institution: Levy, Rona L.; Professor; None; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: U.S. health care costs may reach $2 trillion by the year 2000. Over- utilization is one of the major reasons given for rising health care costs. Illness behavior patterns, including health care utilization and disability days, run in families, and parental modeling and reinforcement have been proposed as likely mechanisms to explain family aggregation patterns. However, studies of parental reinforcement of illness behavior have been limited by retrospective reports from adults about their childhood experiences. The first aim of this study is to assess the way parents respond to their children's somatic complaints and to assess the relationship of parental reinforcement and modeling to various measures of illness behavior in their children. The long term goal is the development of an intervention model for prevention or reducing inappropriate illness behavior. A second aim is to determine whether the effects of modeling and reinforcement are independent of the psychosocial variables of family stress, competence, and parent and child psychological symptoms in determining child illness behavior. The proposed study will focus on gastrointestinal illness behavior in the children of adults with irritable bowel syndrome (IBS). Subjects will consist of children aged 8-16 years whose mothers have sought care for IBS from a defined managed care (HMO) population, control children whose mothers have sought care for asthma. All families will be randomly selected from the same population. For the IBS and non-IBS controls, questionnaire, interview and diary data will be obtained from parents and children on illness behavior, reinforcement, psychological symptoms, stress coping, and beliefs about illness, and school attendance data will be obtained from the schools. For all subjects, data will be collected from the HMO database on number, cost, type, and diagnosis for all parent and child health care visits. Data from the HMO and schools will be obtained prospectively for two years after entering the study and retrospectively for the two years prior to entering the study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYMPTOMS

INTESTINAL

GAS

DYNAMICS

AND

FUNCTIONAL

GUT

Principal Investigator & Institution: Azpiroz, Fernando; Vall D'hebron Foundation Pg Vall D'hebron, 119-129 Barcelona,

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Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS AND MODULATION OF VISCERAL PAIN Principal Investigator & Institution: Gebhart, Gerald F.; Professor and Chair; Pharmacology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-JUL-1983; Project End 30-JUN-2005 Summary: (adapted from applicant's abstract): Visceral pain, particularly visceral hyperalgesia such as is associated with the functional bowel disorders like irritable bowel syndrome, is poorly understood. Because functional bowel disorders are characterized by increased sensitivity to gastrointestinal stimulation, pain and discomfort, they represent a visceral hyperalgesia. Increasing interest over the past decade or more has contributed significant knowledge about visceral pain mechanisms. The current application proposes to build on this base of knowledge to develop and characterize models of visceral hyperalgesia that relate closely to clinical conditions typified by irritable bowel syndrome. Specifically, this proposal will focus on examination and characterization of peripheral contributions to the development and maintenance of visceral hyperalgesia. The first aim will be to develop appropriate models of irritable bowel syndrome and contrast those models with a model of colonic inflammation/colitis. It is hypothesized that changes in the excitability of visceral sensory fibers contribute significantly to development of visceral hyperalgesia and the second aim of this proposal will be in vivo electrophysiological examination of pelvic nerve afferent fiber excitability. Because increases in excitability of pelvic nerve sensory fibers must arise from changes in the function of ion channels or receptors in their cell bodies and terminals, the third aim of this proposal is to study the excitability of identified colon sensory neurons. These aims are a logical extension of the current project and will continue important investigations into the mechanisms of visceral hyperalgesia. The proposed experiments comprise a quantitative study of visceral hyperalgesia, pelvic nerve sensory afferent fibers and colon sensory neurons that will lead to better understanding of the mechanisms responsible for visceral hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF CHRONIC VISCERAL HYPERALGESIA Principal Investigator & Institution: Al-Chaer, Elie D.; Professor; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 05-APR-2001; Project End 31-MAR-2005 Summary: Visceral hyperalgesia is a hallmark of the irritable bowel syndrome (IBS), an extremely common disorder, affecting up to 15 percent of the US population with a major socioeconomic impact. Our understanding of the hyperalgesia in functional pain syndromes such as lBS lags behind our knowledge of the mechanisms of other types of visceral pain that are mechanically-induced or caused by inflammatory reactions mainly because of the lack of a valid animal model. Recently, it was shown that functional abdominal pain can be modeled in animals. Colon irritation (CI) in neonatal but not adult rats, can cause a long lasting visceral hyperalgesia that persists long after the initial injury has resolved. In this study, the central hypothesis is that persistent colonic hyperalgesia, residual to neonatal colon irritation, is associated with central neural sensitization maintained by an interactive exchange of information between the spinal cord and thalamus. HYPOTHESIS 1: There exists a postnatal window of time when

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minimal colon irritation can induce permanent changes in the nervous system that leads to chronic visceral hyperalgesia. SPECIFIC AIM] will define this window of time in postnatal development using noxious mechanical distension or chemical irritation of the colon to cause chronic visceral hyperalgesia. HYPOTHESIS 2: The persistent visceral hyperalgesia residual to neonatal CI is maintained by central plastic changes in neuronal sensitivity. SPECIFIC AIM 2 will demonstrate with immunocytochemistry and electrophysiology, that the chronic visceral hyperalgesia is associated with neuronal sensitization in the spinal cord and the thalamus. HYPOTHESIS 3: The sensitization is maintained in part by neuronal mechanisms involving glutamatergic and peptidergic processes. SPECIFIC AIM 3 will determine if blockade of glutamate or neurokinin receptors by specific antagonists will reduce the central sensitization. HYPOTHESIS 4: The central sensitization is maintained by an intact dorsal column (DC) participating in a feed-forward dynamic exchange of information between the dorsal horn of the spinal cord and the thalamus. SPECIFIC AIM 4 will demonstrate, using electrophysiology and behavior studies, that the sensitization is mediated by an intact DC-thalamus communication that maintains thalamic sensitization and amplifies spinal neuronal sensitivity via descending pathways. The long-term objective of the proposed study is to define the neurophysiological correlates of chronic visceral hyperalgesia and hence to identify novel therapeutic targets for the relief of pain in patients with functional bowel disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANOTRANSDUCTION IN INTESTINAL SMOOTH MUSCLE CELLS Principal Investigator & Institution: Farrugia, Gianrico; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-DEC-2002 Summary: Mechano-gated ion channels provide a mechanism for cells to respond directly to changes in their environment and are involved in several key cellular functions including cell division, regulation of volume, muscle tone and muscle.hypertrophy. Neurons, cardiac, and vascular smooth muscle cells have mechano-gated ion channels. However, the presence and significance of mechano-gated ion channels in gastrointestinal smooth muscle is unknown. The objective of this proposal is to establish the physiological importance of mechano-gated ion channels in single human and canine jejunal circular smooth muscle cells. The Preliminary data obtained by the PI suggest that membrane stretch, increase in cell volume, and cytoskeletal manipulation modulate the whole cell current in human and canine jejunal circular smooth muscle cells. Based on these preliminary data the working hypothesis of this proposal is that mechano-gated ion channels are present on smooth muscle cells and that activation of the channels results in changes in ionic flux and membrane potential, ultimately resulting in changes in intestinal contractility. There are three specific aims: (1) to determine if a change in shape or size of human and canine jejunal circular smooth muscle cells activates mechano-gated channels; (2) to determine which ion channel or channels underlies the increase in whole cell current evoked by a change in cell size or shape; and (3), to determine if regulation of mechano-gated ion channel open probability is dependent on the cellular cytoskeleton. The development of a dissociation technique for obtaining healthy human small intestinal smooth muscle cells by the PI will enable the use of patch clamp recordings and immunofluorescent techniques to address the three specific aims. The demonstration of mechano-gated ion channels in gastrointestinal smooth muscle will provide a novel pathway by which small intestinal

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Irritable Bowel Syndrome

smooth muscle cells can directly and appropriately respond to changes in their environment. Activation of mechano-gated ion channels may be of physiological significance in the smooth muscle response to changes in intraluminal pressure in normal digestion, and of pathophysiological significance in inflammatory or obstructive diseases such as Crohn's disease and strictures and in irritable bowel syndrome where mechano-gated ion channels may be overexpressed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEDIAL PAIN INPUTS TO MONKEY ANTERIOR CINGULATE CORTEX Principal Investigator & Institution: Vogt, Brent A.; Neuroscience and Physiology; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Anterior cingulate cortex is the most frequently activated cortex in human pain studies and is comprised of perigenual and midcingulate regions. Nociceptive information passes through the midline and intralaminar thalamic nuclei, however, links between the spinothalamic tract and spinoreticulothalamic system to the midline nuclei has never been made directly to cingulate cortex. A case of irritable bowel syndrome with severe visceral pain shows alleviation of symptoms with psychotherapy and reduced midcingulate and increased anterior insular activity. Two hypotheses guide these studies: Functions of perigenual areas 32, 25, 24a-c and midcingulate areas 32' and 24a'-d are driven by different midline thalamic inputs and these nuclei conduct parallel circuits for nociception and stress. Each animal will receive horseradish peroxidase either in the spinal cord or dorsocaudal medullary reticular nucleus, and three fluorescent dextran amine retrograde tracers in contralateral cingulate and/or insular areas followed by reactions for 4 antibodies. Specific Aim #1 will evaluate the immunoarchitecture of the midline and dorsocaudal medullary nuclei with a neuron-specific antibody and antibodies for neurofilaments and calbindin. #2 will determine the projections of the midline nuclei to perigenual, midcingulate, and insular cortices with multiple fluorescent tracers that have the same uptake, transport, and signal properties. #3 will evaluate the topography of inputs to the midline nuclei with anterograde horseradish peroxidase following cervical spinal cord injections. #4 will assess the topography of inputs to the midline nuclei with horseradish peroxidase in the dorsocaudal medullary nucleus. #5 will evaluate overlap of dopamine-13 hydroxylase in each of the midline nuclei with inputs from spinothalamic and medullary nuclei to determine the overlap of nociceptive and stress circuits in the thalamus. These studies will provide the first evidence for differential projections of the midline thalamus to limbic cortex and the extent of spinothalamic, medullary, and locus coeruleus overlap in the medial thalamus and modulatation of sensory, affective, and motor domains of pain processing in anterior cingulate and insular cortices. The mechanisms of medial pain system processing will be identified and this will help interpret human imaging studies and assist in developing objective cdteria and therapies for treating the psychiatric consequences of chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDICAL HISTORY, MEDICATIONS, AND PANCREATIC CANCER RISK Principal Investigator & Institution: Mandelson, Margaret T.; Associate Investigator; Center for Health Studies Seattle, Wa 98101

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Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Risk factors for pancreatic cancer are not well established. The goal of this pilot study is to investigate the relation between medical history, medication use and pancreatic cancer in a case-control study based on medical record abstraction and electronic laboratory and pharmacy data. Our specific aims are: 1. To investigate the relation between medical conditions and pancreatic cancer risk, focusing on: a. Diabetes mellitus, including disease duration, therapy, and glycemic control. b. Pancreatic inflammation, including acute and chronic pancreatitis. c. History of peptic ulcer disease and/or infection with Helicobacter pylori (H. pylori). d. History of cholecystectomy and/or cholelithiasis. 2. To investigate the relation between the use of medications and pancreatic cancer, focusing on nonsteroidal anti-inflammatory drugs, cholesterol lowering agents including HMG-CoA reductase inhibitors and acid suppressive medications including histamine receptor antagonists and proton pump inhibitors. As a secondary specific aim we propose to examine additional medical conditions and medications in order to generate hypotheses for future studies of the epidemiology and prevention of pancreatic cancer. These include evaluation of medical conditions such as irritable bowel syndrome, allergies and asthma as well as medications including immunosuppressive medications and angiotensin converting enzyme inhibitors. To meet these specific aims we propose to conduct a case-control study of pancreatic cancer comprised of 250 newly diagnosed cases and 1,000 controls in the defined population of Group Health Cooperative, a large health maintenance organization. Data on prior medical conditions and medications will be collected through abstraction of traditional and computerized medical records, including electronic laboratory and pharmacy data. Study strengths include the availability of uniformly collected, long-term medical and pharmacy data and the availability of data on important covariates, including smoking. The proposed study will provide a unique opportunity to investigate the role of medical conditions and medications in pancreatic tumorigenesis and to generate new insights into the mechanisms that result in pancreatic cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTER TRIAL OF FUNCTIONAL BOWEL DISORDERS Principal Investigator & Institution: Drossman, Douglas Arnold.; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-AUG-2003 Summary: The primary aim of this study is to compare the efficacies of clinical treatments for the group of chronic, painful functional bowel disorders (FBD) that predominantly affect women. Secondary aims include 1) determination of demographic, psychosocial, physiologic and symptomatic predictors of clinical improvement and 2) analysis of significant relationships among physiologic markers of FBD, psychosocial status, symptoms and treatment effects. The Principal Investigator and his colleagues propose to compare cognitive-behavioral psychological treatment with antidepressant drug therapy (desipramine) and education/attention placebo in over 300 women. Interrelationships between psychological and physiological factors on the development, clinical expression and treatment of FBD have long been recognized, but this is the first large-scale study designed both to isolate therapeutic effects, and to investigate interactions among physiologic measures, psychologic and sociodemographic factors, severity of symptoms, and therapeutic improvement including quality of life. In the proposed plan of research, at least 300 female patients (aged 18- 65) with FBD (irritable bowel syndrome, painful constipation and/or functional abdominal pain) will be

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Irritable Bowel Syndrome

enrolled in clinics at UNC-Chapel Hill and Toronto, Canada. A severity index will determine recruitment into the group of moderate FBD (200 patients) and severe FBD (100 patients). Each group will be randomized into the three treatment arms (cognitivebehavioral treatment, desipramine, and education/attention placebo), treated over a 12week period, and followed for one year. Outcome measures will include symptoms (standardized abdominal pain, stool form, and frequency) using diary cards, daily functional status (Sickness Impact Profile), depression (HAM-D), and psychological distress (SCL-90), physiological measures (enhanced rectal motility and visceralsensation), and health care use. Multivariate statistical methods with a hierarchical design will be applied to the data to assure maintenance of statistical power over multiple tests of overlapping groups. The results of this study may significantly improve an understanding of this complicated syndrome that lowers the quality of life and economic productivity of large numbers of women. The clinical impact of the study, in providing physicians with scientific evidence of the efficacy of treatments of FBD that are commonly used in practice, may be significant. This study may provide clinicians with predictors of success among types of FBD patients and types of therapy that will improve symptoms and quality of life and reduce the health care costs associated with this common syndrome, while improving patient-physician satisfaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROCHEMICAL MECHANISMS OF VISCERAL PAIN Principal Investigator & Institution: Traub, Richard J.; Associate Professor; Oral & Craniofacial Biol Scis; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-AUG-1999; Project End 31-MAY-2007 Summary: (provided by applicant): Irritable Bowel Syndrome (IBS) is characterized by abdominal pain in the absence of pathology. Epidemiological studies further show IBS is reported most often in menstruating women compared to post-menopausal women or men suggesting gonadal hormones could be a contributing factor. It was recently hypothesized that the pain of IBS could result from sensitization of visceral afferent fibers or hyperexcitability of dorsal horn neurons. Recent data suggests a role for spinal NMDA receptors in processing noxious and innocuous visceral stimuli and NMDA receptors in the brain are modulated by estrogen. The long-term goal of this application is to examine the effects of estrogen on spinal NMDA receptor-mediated processing of noxious and innocuous colorectal stimuli. We hypothesize that estrogen increases activity at spinal NMDA receptors in the absence and presence of colonic inflammation leading to colorectal allodynia and hyperalgesia. This modulation may result from alterations in NMDA receptor subunit composition or second messenger mediated phosphorylation. Using our model of colorectal distention (CRD), we will test these hypotheses by examining the effects of estrogen replacement in ovariectomized rats on visceral sensory processing in the spinal cord in the absence and presence of colonic inflammation, in the following specific aims: 1) Determine the effects of estrogen on responses to transient innocuous, noxious and inflammatory colorectal stimuli. Behavioral, immunocytochemical and electrophysiological studies will test the hypothesis that estrogen facilitates responses to CRD in the absence and presence of colonic inflammation. 2) Characterize the effects of estrogen on subpopulations of visceroceptive projection neurons using retrograde tract tracing and immunocytochemical localization of Fos expression. This will test the hypothesis that estrogen alters the percentage and segmental distribution of supraspinal projection neurons that respond to CRD in the absence and presence of colonic inflammation. 3) Determine if NMDA receptor-mediated modulation of viscerosensory processing is

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affected by ovariectomy and estrogen replacement. This will test the hypothesis that the modulation of responses to CRD by estrogen is due to altering activity at NMDA receptors. 4) Determine the mechanism(s) through which estrogen modulates CRDevoked NMDA receptor activity in the absence and presence of colonic inflammation. This will test the hypothesis that estrogen alters NMDA receptor subunit composition and/or modulates second messenger-mediated phosphorylation of tile NMDA receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROIMMUNE MECHANISMS OF VISCERAL HYPERALGESIA Principal Investigator & Institution: Pezzone, Michael A.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 15-APR-1999; Project End 31-JAN-2004 Summary: The applicant for this Mentored Clinical Scientist Development Award is currently completing a Fellowship in Gastroenterology and Hepatology at the University of Pittsburgh Medical Center. During his training to obtain combined M.D. and Ph.D. degrees under the mentorship of Bruce Rabin, M.D., Ph.D., the candidate investigated extensively the neural and neuroendocrine mechanisms of stressor-induced immune alterations int he rat, focusing specifically on stress-activated CNS pathways that may modulate lymphocyte function. In these studies, the candidate identified stress-activated neurons in the rat CNS by using c-FOS expression as a marker of neuronal stimulation following acute footshock and conditioned stress. To further his career in academic medicine and to further develop his expertise in neuro-immune interactions and stress, the candidate has designed this research proposal to assess the roles of stress and intestinal inflammation in the development of visceral hyperalgesia in the gut. This model of colonic inflammation (trinitrobenzenesulfonic acid in ethanol) appears to be propagated by cells of the immune system and is subsequently modulated by stress. Understanding the pathophysiologic roles of these factors in the sensitization of gastrointestinal afferents will help further provide important information regarding the etiology and clinical course (including relapse) of painful bowel disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Methods encompassing intestinal electrophysiology, neuropharmacology, histology, and mast cell growth factors will be used to evaluate, in a hapten- induced model of colonic inflammation, the chemical dialog between afferent nerves and inflammatory/immune cells is likely to contribute to the sensitization of gastrointestinal afferents in pathological conditions such as IBS and IBD. This dialog may be modulated by activity in autonomic pathways to the gut and/or by chemicals released from the pituitary gland during stress. Combining these new skills with those previously acquired, the applicant will be well-suited to study a variety of gastrointestinal disease states in addition to characterization of the neuroimmune mechanisms of visceral hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURONAL CONTROL OF INTESTINAL MOTILITY IN MUTANT MICE Principal Investigator & Institution: Heuckeroth, Robert O.; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The proposed studies will systematically examine the cells that control intestinal motility in a panel of mutant mice created by NIH funded mouse mutagenesis projects. This will include anatomic evaluation of the enteric

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Irritable Bowel Syndrome

nervous system, the Interstitial Cells of Cajal (intestinal pacemaker cells), and sympathetic innervation to the gut. In addition, the principal investigator will use a recently described imaging technique (diolistic labeling) to examine intestinal smooth muscle, and perform functional motility analysis in mutant mice. The long-term objective of these experiments is to identify novel mutations that affect intestinal motility. These studies are important because defects in intestinal innervation and motility cause significant morbidity and mortality. Medical problems associated with abnormal intestinal motility include Hirschsprung's disease, intestinal pseudoobstruction, and irritable bowel syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NK CELL ACTIVITY AND IBS ACROSS THE MENSTRUAL CYCLE Principal Investigator & Institution: Motzer, Sandra A.; Assistant Professor; Biobehavioral Nursing and Health Systems; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: The purpose of this study is to compare natural killer (NK) cell percentage and activity across the menstrual cycle in women with and without irritable bowel syndrome (IBS). NK cells are unique amongst immune cells because their percentage and activity vary in response to many emotional, cognitive and physiological stressor (e.g., anxiety, depression, perceived lack of personal control, bereavement, and exercise). Cognitive/emotional stressors are often experienced by persons with chronic health disturbances. Further, NK function many be amenable to change with interventions targeting distress in normal persons, ill persons, or their caregivers. This study will compare a sample of women with a chronic health disturbance Further, NK function may be amenable to change with interventions targeting distress in normal persons, ill persons, or their caregivers. This study will compare a sample of women with a chronic health disturbance, IBS, with control women without chronic gastrointestinal (GI) symptoms. Differences in physiological arousal and immune function will be examined within the context of menstrual cycle phase. This study is innovative in that it is designed to examine the relationship between stress-related psychological and physiological variables and immune function within the context of menstrual cycle phase in 2 groups of women, one symptomatic without an identified underlying inflammatory component but with evidence of physiological arousal (HPA axis and SNS activation) and another as control. Prior research by others has documented elevated stress hormone levels in women with IBS. Preliminary data suggest innate immune function differs in women with and without symptomatic IBS. Specific aims are to: 1) describe the levels of specific immune function markers across menstrual cycle phases, and test for cycle phase and group difference sin normally menstruating women with and without IBS; 2) extend and affirm the work of others by describing levels of stress and ovarian hormones, and self-report distress across 3 menstrual cycle phases, and by testing for cycle phase and group differences in these variables; and 3) examine the relationship of immune function to measures of physiological arousal, physical and psychological distress, and ovarian hormones during each menstrual cycle phase. Descriptive and correlational statistical and repeated measures ANOVA will be used in data analysis. If a relationship exists between chronic distress and NK cell function, there would be important clinical implications for identifying women at risk for experiencing chronic distress, and for developing and testing interventions targeting distress reduction in vulnerable populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NON-ADDICTING CANNABINOID MEDICATIONS Principal Investigator & Institution: Malan, Thomas P.; Anesthesiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2006 Summary: (provided by applicant): As a physician, I see many patients with medical conditions for which adequate therapy is not available. CB2 cannabinoid receptorselective agonist medications may prove useful in treating some of these disease states. One is moderate-to-severe pain, where the use of opioid medications, the most effective therapy, is often limited due to concerns over addiction. In addition, opioids prescribed as analgesics are subject to diversion and abuse. We have shown that CB2 receptorselective agonists produce strong antinociceptive effects in animal models, suggesting that they may be useful as analgesic medications for humans. Unlike cannabinoids with agonist activity at CB1 receptors, CB2 receptor-selective agonists are predicted not to produce the rewarding properties associated with drug abuse, since CB2 receptors are not found in the CNS. By reducing the need for opioids, CB2 receptor-selective medications would diminish the problem of addiction with its severe individual and social costs. CB2 receptor-selective agonists, however, are likely to have important medical applications beyond analgesia. In this proposal, we hypothesize that CB2 receptor-selective agonists will be useful in the treatment of the prevalent and challenging problems of urinary incontinence; irritable bowel syndrome, inflammatory bowel disease and visceral hypersensitivity; and opioid resistant neuropathic pain. Our goal is to combine state-of-the-art chemistry and biology to develop CB2 receptorselective agonists as medications. Aim one will test the hypothesis that CB2 receptorselective agonists will have therapeutically desirable properties beyond analgesic effects. We will explore the activity of CB2 receptor-selective agonists in experimental models relevant to urinary incontinence; inflammatory bowel disease and other conditions associated with sensitization or increased activity of C-fibers. We will also test the hypothesis that CB2 receptor-selective agonists will not produce a withdrawal syndrome or provide reward. Aim two will use a lead optimization strategy to improve the medicinal properties of AM1241, our structural lead compound. This will be accomplished by a structure-activity relationship study involving the systematic manipulation of each of the molecule's pharmacophoric groups using drug design principles. Novel compounds will be evaluated for their affinity at and selectivity for CB2 cannabinoid receptors in vitro and for desired properties in vivo. The successful completion of these aims will provide physicians a therapeutic option that may provide relief for patients with difficult medical conditions and decrease the use of opioids, minimizing opportunities for abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NORADRENERGIC DYSFUNCTION--A MODEL OF FIBROMYALGIA PAIN Principal Investigator & Institution: Jasmin, Luc; Neurological Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: The goal of this project is to develop a rat model of fibromyalgia pain which could provide the basis for future research into this complex disease. The difficulty in finding an etiology for this painful condition is in part because fibromyalgia is not a discrete or unique disease, but patients also a display number of different symptoms in addition to the widespread tenderness, including fatigue, sleep disturbances, headaches,

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gastrointestinal symptoms, etc. As such, fibromyalgia overlaps conditions such as Chronic Fatigue Syndrome, Irritable Bowel Syndrome, tension and migraine headaches. These conditions share several features, including a female predominance, initiation or exacerbation in response to several different types of "stressors", and response to similar types of pharmacologic and non-pharmacologic modalities (e.g. tricyclic drugs, aerobic exercise). A dysfunction of the noradrenergic system, the basis for the proposed model, presents a unifying explanation for many seemingly disparate findings in fibromyalgia by accounting for the neuroendocrine and autonomic abnormalities, in addition to the chronic pain. Our guiding hypothesis is that in fibromyalgia, chronically decreased noradrenergic input to the spinal cord facilitates substance P release and subsequent hyperalgesia (decreased threshold for pain). This hypothesis is based on both clinical evidence of decreased noradrenaline and increased substance P in the spinal cord of fibromyalgia patients, as well as evidence from basic research demonstrating that acute decreases in spinal noradrenaline allow for greater release of substance P and sustained hyperalgesic effects of this neurotransmitter. These alterations in turn result in greater expression and redistribution of the substance P receptor in the spinal cord, contributing to the chronicity of the hyperalgesia. In the female rat, we will apply a novel technique of selective immunolesion of brainstem noradrenergic input to nociceptive areas of the spinal cord. The first aim will test the hypothesis that lowered nociceptive thresholds in rats with decreased spinal noradrenaline depend on substance P neurotransmission. This hypothesis will be tested by determining the contribution of spinal SP neurotransmission in alterations of nociceptive behavioral and neuronal responses to noxious and innocuous stimuli. The second aim will test the hypothesis that chronically decreased spinal noradrenaline chronically increases basal levels, and facilitates evoked release of substance P, by measuring levels of substance P in the CSF, primary afferent neurons, and spinal cord, both basal and following noxious and innocuous stimulation. In the third aim, we will test the hypothesis that decreased spinal noradrenaline facilitates stimulus-induced increased expression and redistribution of the substance P receptor (NK1 receptor) in the spinal cord by measuring basal and noxious stimulus-induced alterations in the expression of this receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL DRUG DISCOVERY TOOLS FOR DEPRESSION AND ANXIETY Principal Investigator & Institution: Nanda, Steven A.; Promoter Neurosciences, Llc 505 S Rosa Rd, Ste 52 Madison, Wi 53719 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Stress is a significant factor that can precipitate, exacerbate, and maintain psychopathology. The corticotropin-releasing factor (CRF) system has been implicated in mediating the stress response and linking it to psychopathology. Over-activity of the CRF system is implicated in depression, anxiety, and perhaps other stress-related disorders such as irritable bowel syndrome. Abundant preclinical evidence indicates that treatments targeting this system offer a promising approach for treating certain neuropsychiatric, as well as, other stress-related physical illnesses. Promoter Neuroscience (PNS) has developed intellectual property related to the promoter sequences of the CRF family of genes and is developing screening tools for drug discovery. PNS has demonstrated the feasibility of using cell cultures transiently transfected with CRF system promoter reporter constructs as high throughput screening tools. The proposed studies will further develop PNS's proprietary technologies and

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help accelerate the discovery of compounds capable of altering expression of the CRF system. To improve this technology and to make a drug-screening tool relevant to humans, we will transfer our technology to human cortical neuronal cultures, which are derived from a brain region that naturally expresses CRF receptors and has been implicated in mediating the psychopathology. One set of cells will be transfected with constructs containing the human CRF receptor 2a (CRF2a) promoter driving expression of the Lucifer's reporter gene. Separate cortical neuronal cultures will be stably transfected with constructs containing the luciferase reporter gene under control of the human CRF receptor 1 (CRF1) promoter. Studies will characterize the basal levels of expression from the stably transfected cultures. To begin to explore potential new therapeutic approaches, expression from the stably transfected cultures will be monitored following treatment with compounds known to activate several different intracellular pathways. Activation of these intracellular pathways will lead to stimulation of transcription factors that bind to putative cis-regulatory elements identified within the CRF1 and CRF2a promoter regions. The stably transfected human cortical neuronal cultures will provide models relevant to human brain function that will provide PNS with the potential to discover new drugs that regulate CRF receptor expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORWH: SCOR ON SEX AND GENDER FACTORS AFFECTING WOMEN'S * Principal Investigator & Institution: Greenspan, Joel D.; Associate Professor; Basic Dental Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This multidisciplinary SCOR is devoted to the study of the mechanisms of chronic or persistent pain with specialized focus on 1) sex-related factors that influence pain, and 2) painful clinical conditions that demonstrate a high prevalence in women. The Center's research program is diverse, and ranges from molecular studies to systems physiology studies to clinical studies. Our working model is that research on pain has clearly shown that a person's sex is an important factor in determining their perception of, and response to, painful stimulation and pathological pain. Several physiological and psychological mechanisms have been proposed to account for these sex differences, yet many hypotheses remain to be adequately tested. This SCOR would direct its efforts to evaluating physiological models of sex-related pain differences, including the influence of gonadal hormones. Additionally, this Center would evaluate pathophysiological models of chronic pain conditions that are more prevalent in women, focusing on temporomandibular joint disorders (TMD) and the visceral pain associated with conditions such as irritable bowel syndrome (113S). This Center would facilitate the transfer of basic scientific knowledge to the study of persistent pain in humans, and ultimately to the development of new methods of diagnosing and treating these conditions in the general population. One clinical and two basic science projects constitute the scientific basis of the application. The two principal objectives of this SCOR are: 1) To elucidate the underlying mechanisms associated with sex differences in persistent pain of deep muscle and visceral origin. Human and animal studies will explore hypothesized physiological mechanisms of sex differences in pain, including opioid receptor expression, peripheral nociceptor sensitivity, CNS sensitization, and CNS ascending/descending modulation, as well as the influence of gonadal steroids on these mechanisms. All three projects address this objective. 2) To explore the neural basis of temporomandibular disorder (TMD) pain, with special

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emphasis upon sex-related hypotheses. TMD is the major persistent orofacial pain condition of deep tissue origin. It shows a large prevalence in women of childbearing age. The pathophysiology of TMD is poorly understood, but several hypotheses based on sex-related factors have been proposed. Two of the proposed projects (#1and #3) direct efforts explicitly to evaluate such hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: P2: SEX DIFFERENCES IN THE COLONIC RESPONSES TO STRESS: ROLE OF CRF PATHWAYS Principal Investigator & Institution: Tache, Yvette F.; 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: Stress is implicated as the causative or complicating factor of symptoms of several diseases including altered bowel habits and visceral hyperalgesia in Irritable Bowel Syndrome (IBS) patients. Our previous work as well as other studies show that the activation of corticotropin-releasing factor (CRY) receptors mediates various stressors-induced alterations of gut motor function and that CRF1 receptor is mostly involved in the colonic response. Recent evidence also suggests a role of this pathway in stress-relatcd colonic hypersensitivity to colorectal distention. Despite the greater prevalence of stress-related IBS symptoms in women, most of the experimental knowledge of the effects and mechanisms of stress on gut motor alterations and visceral hyperalgesia derives from studies performed in male rodents. The overall goal of the proposal is to characterize the neuroanatomical and biochemical substrata underlying for sex-related differences in stress-induced colonic responses (motility and visceral pain) in rats. Based on presence of estrogen responsive elements on the CRF gene and its modulation by estrogen in the hypothalamus, we will test the hypothesis that estrogeninduced modulation of CRF signaling pathways contributes to the enhanced colonic responses of female rodents to stress. In the specific aim 1, we will build on our data preliminary data and characterizes sex-related differences in stress-induced colonic motor activation and visceral hyperalgesia using psychological and visceral stressors in model of IBS. We will assess with the newly developed CRF1 and CRF2 selective receptor antagonists the role of activation of CRF receptors in stress-related colonic responses in female rats and modulation by sex hormones. In specific aim 2, we will define the sex-related differential activation of brain, spinal and enteric circuitry induced by stress, particularly at neuronal sites involved in autonomic and pain modulation and known to express estrogen receptors using Fos expression as a marker of neuronal activation. Double labeling will be used to identify the presence of estrogen receptors and identified CRF and/or oxytocin and noradrenergic neurons. Specific Aim 3 will determine the modulation of CRF and CRF1 gene transcription by estrogen at specific sites involved in the colonic responses to stress. The regulation of rat and human CRF and CRF1 receptor promoter activity by estrogens will be further investigated in naive and transfected cells. These studies using functional, neuroanatomical, neurochemical and molecular approaches in rodent model will provide new insight on the interactions between estrogens and CRF pathways as it relates to the visceral response to stress and the underlying mechanisms at the levels of gene regulation and will have relevance to the pathophysiology of stress-related exacerbation of IBS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: P3: SEX DIFFERENCES IMMUNOLOGIC RESPONSES IN IBS

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Principal Investigator & Institution: Chang, Lin; 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: Studies support a prominent role of stress in irritable bowel syndrome (IBS). The principal branches of the general stress response are the hypothalamic-pituitaryadrenal (HPA)axis and the sympathetic nervous system (SNS). The overall hypothesis of this Project is that females and males differ in their HPA axis responsiveness and SNS activation, particularly under stress conditions, and that these differences will help explain the greater vulnerability of females to develop chronic stress-related conditions such as IBS. Furthermore, these sex-related differences in the HPA and SNS are reflected in differences in colonic mucosal immune modulation which in turn relates to the higher prevalence of colonic visceral hypersensitivity in female IBS patients. We will study four subject groups: female IBS patients, male IBS patients, female controls and male controls. In Aim 1, we will test the hypothesis that under basal conditions, males have greater HPA (ACTH, cortisol) and general SNS (cardiosympathetic and sympathoadrenal) activity but females may have greater SNS activity to the pelvic organs. Specifically, we will compare HPA responsiveness in males and females using HPA axis challenge tests, biomathematical modeling analysis to characterize the diurnal rhythm of ACTH and cortisol, and estimate chronically enhanced SNS output to the colon by measuring tissue NE levels and alpha 2-receptor density in colonic biopsies. In Aim 2, we will test the hypothesis that under stress conditions, males show greater general measures of plasma HPA (ACTH, cortisol) and SNS activity (cardiosympathetic, catecholamines and skin conductance) responses to a visceral stressor (flexible sigmoidoscopy) and a psychological stressor (Trier social stress test) compared to females. In Aim 3, we :will test the hypothesis that symptomatic IBS patients have: altered plasma and mucosal cytokine production which differ in females and males and are related to sex-related differences in visceral pain perception. We will measure plasma and colonic mucosal cytokine markers, and perceptual responses to rectal balloon distension to determine if visceral sensitivity is associated with mucosal and plasma immune markers. The combination of experimental approaches should improve our understanding of the sex-related differences in stress response mechanisms underlying functional pain syndromes. 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

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neurological abnormalities present in human patients with IC. They also are intended to guide the choice of subsequent studies toward the primary systems involved in IC, with the eventual goal of identifying rational treatments of IC in human beings. The overall objective of this proposal is to test the hypothesis that interactions between CRF, sex hormones and the alpha-2 adrenoceptor (alpha2-AR) play a role in the sex difference in stress-responsiveness of cats with FIC. The rationale for the proposal is based on 1) clinical evidence that females are more prone to develop IC than males (intact males in cats), 2) the gap in knowledge in factors that may account for such sex differences due to the paucity of experimental data in this field, 3) evidence from our recent studies pointing to a role of alpha2-AR dysfunction in cats with IC, and 4) existing evidence that urothelial and alpha2-AR function can be modulated by testosterone, estrogen, and oxytocin. By studying a natural occurring animal model of IC which shares many features with a rat model of IBS, and with the respective human patient populations, we will be able to assess the role of sex hormones on the expression of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POPULATION BASED TWIN STUDY OF CHRONIC FATIGUE SYNDROMEN Principal Investigator & Institution: Sullivan, Patrick F.; Associate Professor; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001 Summary: Despite considerable research, fundamental questions about CFS-like illness remain at best partially answered. These questions include its definition, validity, the degree to which it results from genetic versus environmental factors, and the nature of the substantial comorbidity observed with other conditions. The overarching aim of this Project is to shed light on a number of basic questions about CFS via a large populationbased classical twin study. First, we will screen approximately 13,000 same-sex twin pairs who are members of the Mid-Atlantic Twin Registry for the lifetime presence of CFS-like illness (and several overlapping conditions such as fibromyalgia and major depression). Second, all twins who screen positive and a subset of twins who screen negative will be directly and blindly interviewed. The interviews will collect information about CFS symptoms, psychiatric disorders, stress life events, and medical history, and medical history. We will obtain additional standardized medical data via the subject's physician(s). Third, all screening, direct interview and medical data will be independently reviewed by three of the study investigators to determine the certainty than an individual meets criteria for "presumptive CFS" plus approximations of the Centers for Disease Control, British, and Australian CFS case definitions. Obtaining these unique data will allow us to address a set of critical questions regarding CFS-like illness. First, using the direct interview data will allow us to address a set of critical questions regarding CFS-like illness. First, using the direct interview data, we will use multivariate techniques to derive and empirical typology of prolonged fatigue and to assess how this typology compares to the major CFS case definitions to answer the question: "Is there a point of rarity that distinguishes the common symptom of fatigue from case definitions of CFS"? Next, we will quantify the role of genetic predisposition and environmental sources of variation from different definitions of CFS-like illness. This will allow us to address 2 important questions. Because the degree to which a complex and idiopathic condition is heritable is an important validator, we can address the question: "Do these definitions yield similar or different estimates of heritability?" In addition, examining the extent to which liability to CFS- like illness is due to additive genetic, shared environmental, and individual-specific environmental precipitating

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effects will yield glimpses into the fundamental nature of CFS. Finally, using multivariate twin analyses, we address the question: "To what extent to the genetic and environmental sources of variation of these other conditions overlap with CFS?" Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRESYNAPTIC MECHANISMS IN THE INTESTINE Principal Investigator & Institution: Galligan, James J.; Professor; Pharmacology and Toxicology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 30-JUN-2004 Summary: Presynaptic mechanisms are an important means for neurotransmitters, hormones, paracrine substances and drugs to modulate the activity of myenteric nerves and gut motility. Despite the clear importance of presynaptic mechanisms in regulating neurotransmission in the myenteric plexus, little is known about the details of these mechanisms. The proposed studies are designed to characterize these mechanisms. Electrophysiological methods will be used to study excitatory synaptic transmission between myenteric neurons in acutely isolated preparations of guinea pig intestine and between guinea pig myenteric neurons maintained under tissue culture conditions. These studies will investigate the contributions of acetylcholine (ACh) acting at nicotinic cholinergic receptors and ATP acting at P2X purine receptors, to fast excitatory synaptic potentials (fEPSPs) during long trains of stimulation. As nicotinic receptors desensitize quickly, it is anticipated that ACh will be the predominate transmitter early while ATP will predominate later in the train of activity. Presynaptic mechanisms controlling the release of these two important transmitters will also be investigated. These studies will focus on channels which provide the calcium needed for transmitter release and the presynaptic receptors which facilitate their release. The facilitatory effects of 5-HT4 receptor activation on fEPSPs mediated by ACh and ATP will be investigated. In addition, these studies will investigate the contribution of 5-HT3 and 5-HT4 receptors to excitation of enteric sensory nerve terminals. The role of presynaptic nicotinic acetylcholine receptors (nAChRs) in controlling the release of the slow synaptic transmitters, substance P/neurokinin A will also be investigated. These latter studies will attempt to establish that there are presynaptic nAChRs on the terminals of sensory neurons and that ACh released from sensory neurons facilitates SP/NKA release and enhances slow excitatory synaptic transmission. There are many disorders of gut motility which have their basis either directly or indirectly in alterations in enteric neurotransmission. These disorders include gastroesophageal reflux disease, the irritable bowel syndrome and chronic intestinal pseudo-obstruction. It is anticipated that these studies will provide new insights into mechanisms of synaptic transmission in the gut which could lead to the development of new and effect drug treatments for motility disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PSYCHOPHYSIOLOGY OF IRRITABLE BOWEL SYNDROMEN Principal Investigator & Institution: Whitehead, William E.; Professor of Medicine; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-1993; Project End 30-NOV-2002 Summary: The irritable bowel syndrome (IBS), which is characterized by abdominal pain and altered bowel habits, is the most common gastrointestinal disorder, affecting 9.4 percent of the population. Fifty to 60 percent of IBS patients report pain at

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abnormally low volumes of rectal distention, suggesting that visceral hyperalgesia may be the mechanism for IBS. A cognitive behavioral model is presented which accounts for increased pain sensitivity in IBS by two hypotheses: (1) Two cognitive traits--selective attention on gastrointestinal sensations and attribution of disease significance to these sensations--are the mechanisms by which stress and other factors influence pain perception. (2) Childhood social learning in the form of increased attention for somatic complaints and modeling of sick role behavior by parents, is the most important determinant of selective attention and disease attribution. The differential recall of previously memorized words, depending on their content, will be used to develop a test for selective attention. Words describing gastrointestinal sensations plus control words describing respiratory sensations and neutral words will be tested for a prior probability of recall by healthy subjects. Then IBS patients, patients with lactose malabsorption (an enzyme deficiency producing chronic gastrointestinal symptoms similar to IBS), patients with asthma, and healthy controls will memorize these words, and 15 minutes later will be tested for recall. Other techniques for assessing selective attention which will be compared to the recall task are the Stroop Color Test and recognition of words in the above categories presented briefly by a tachistoscope. The test of disease attribution will be developed by presenting the same gastrointestinal and respiratory sensations and asking subjects to rate whether they could be symptoms of disease. After developing valid and reliable measures, new samples of IBS patients, lactose intolerant patients, and controls will complete these tests of reinforcement and modeling of gastrointestinalrelated sick role behavior and tests of rectal distention pain thresholds. A subsequent study will determine whether experimental stress increases pain sensitivity and progressive muscle relaxation decreases pain sensitivity in IBS patients, and whether these psychological influences on perceptions are associated with changes in selective attention to gastrointestinal sensations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECURRENT ABDOMINAL PAIN IN CHILDREN Principal Investigator & Institution: Shulman, Robert; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-APR-2007 Summary: (provided by applicant) Ten to 17 percent of children between the ages of 4 and 16 years meet the criteria for recurrent abdominal pain (RAP) a condition that accounts for at least 5 percent of all pediatric office visits and often leads to significant disability (e.g., school absence). From 30-60 percent of children with RAP will go on to experience similar pain as adults leading to the suggestion that RAP and irritable bowel syndrome (IBS) may be the same syndrome at different developmental stages. Similar to IBS, 20-68 percent of children reporting abdominal pain also experience alterations in bowel patterns (constipation and/or diarrhea). Although the cause(s) of RAP (as well as IBS) are unknown, factors contributing to the symptom experience, including health care seeking, are likely to include both physiological and psychosocial. The relationships among physiologic abnormalities, psychological makeup, and parental responses/behaviors in RAP are largely unexplored (undefined). To study the contributions of these sets of factors and their potential interplay, we propose to compare three groups of children: those with RAP who are referred to tertiary medical attention (RAP-GI); who have RAP but do not seek medical attention beyond their pediatrician (RAP-Ped); and those who do not have RAP symptoms (Controls). Our Specific Aims are to describe and compare among these children (ages 7-10): 1) GI symptoms (abdominal pain and bowel patterns) and functional disability (pain

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interfering with activity, school absences) using retrospective and prospective symptom measures; 2) autonomic nervous system function (spectral and non-spectral analysis of heart rate variability and urine catecholamines); 3) child and parent pain coping skills, parent modeling and reinforcement of illness behavior; and 4) psychological distress (anxiety, depression, and somatization). Children will be recruited from pediatric practices in Houston. This proposed interdisciplinary study will be the first in children to examine concurrently both physiologic and psychosocial factors related to RAP, and its functional consequences, and to compare these to a sample of children with RAP who do not seek tertiary medical attention. Because so many children with RAP are identified as having IBS when they reach adulthood, this study may provide insight into the developmental progression of this disorder. These data could be used to develop guidelines for use by health care providers to intervene early with children who have this common complaint in order to prevent health care seeking behavior with its attendant financial and emotional cost. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF IMMUNOSUPPRESSIVE MOLECULES IN IBD Principal Investigator & Institution: Jobin, Christian; Assistant Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-1993; Project End 30-JUN-2008 Summary: (provided by applicant): A single layer of intestinal epithelial cells (IEC) protects the host from the toxic luminal environment. These cells are in close proximity with lamina propria immune cells and likely communicate with each other by direct contact and/or secretion of soluble mediators. Interestingly, the mucosa of the distal ileum and colon is constantly exposed to a complex microbial flora, yet no pathological inflammation occurs in normal hosts. This suggests that IEC gene expression must be tightly regulated to avoid overreaction to ubiquitous luminal bacterial products, yet be able to transiently respond to environmental pathogens. Although the repertoire of proinflammatory molecules synthesized by IEC has been identified, little is known about how these cells regulate coordinated expression and suppression of these genes. In addition, the intracellular signaling pathways associated with IEC gene expression are still poorly understood. Finally, the kinetics and distribution of NF-kappaB-activated cells during the course of an intestinal inflammatory process is currently unclear, much less during treatment intervention. We have shown that the NF-kappaB pathway regulates expression of a number of proinflammatory cytokines and adhesion molecules in IEC. Interestingly, native IEC and most transformed colonic cell lines show a unique IkappaBa phosphorylation and degradation process that distinguishes these cells from other cell lineages. Our hypothesis is that normal lEC have a unique NF-kappaB signaling pathway which buffers their cellular responses to the aggressive luminal environment. This hypothesis will be tested by addressing the following SPECIFIC AIMS: 1) Dissect the unique IkappaB/NF-kappaB signal transduction in transformed and native IEC following stimulation with environmentally relevant cytokines and commensal bacteria and explore mechanisms of suppression of this pathway by TGFbeta 2) Determine the physiological role of NF-kappaB in acute and chronic intestinal inflammation and tissue repair by using kappaB-green fluorescence protein transgenic mice with experimental colitis in combination with selective inhibition of the NF-kappaB pathway. Our ultimate goal is to prevent the onset and relapse of inflammatory bowel diseases (IBD) by manipulating key regulatory signaling proteins involved in central inflammatory pathways.

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

Project Title: RISK FACTORS FOR ENDOMETRIOSIS Principal Investigator & Institution: Hunter, David J.; Director; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 03-AUG-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Endometriosis, the third leading cause of gynecologic hospitalization in the United States, remains one of the most enigmatic gynecologic pathologies. Endometriosis is defined as the presence of endometrial tissue outside of the uterine cavity. These implants respond to the hormonal cues of the menstrual cycle and "bleed" as they would in the uterus. The consequence is the development of adhesions, scarring, and painful inflammation. Signs and symptoms include dysmenorrhea, dyspareunia, infertility, dysuria, and irritable bowel syndrome.The effects of the disease can be physically and mentally debilitating with frequent misdiagnoses and poor treatment options. Its prevalence among U.S. women has been estimated to be approximately 10%, [the] time from onset of symptoms to laparoscopically confirmed diagnosis is estimated to average between 6 and 11 years. To date, the etiology of endometriosis remains unknown and few epidemiologic studies exist. Using data on 2,690 laparoscopically confirmed incident cases of endometriosis collected from the Nurses' Health Study II, an ongoing, prospective cohort study that began in 1989, the applicant proposes a study to assess the following hypotheses: a) Women with menstrual characteristics of younger age at menarche, longer time to menstrual regularity, or shorter menstrual cycle length are at higher risk of endometriosis. b) Women with a low waist-to-hip ratio are a higher risk of endometriosis. c) Women with a higher body mass index at age 18 are at lower risk of endometriosis. d)Women who were born with a greater birthweight are at higher risk of endometriosis. All analyses will control for other known and suggested risk factors for endometriosis such as oral contraceptive use and cigarette smoking. The applicant will have more than 90% power to evaluate the above hypotheses. These analyses will be the first prospective data with adequate power to evaluate this important and understudied cause of morbidity among premenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELECTIVE CRF ANTAGONISTS FOR BOWEL DISORDERS Principal Investigator & Institution: Grigoriadis, Dimitri E.; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 921211100 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 01-MAY-2003 Summary: (Applicant's abstract): Corticotropin releasing factor (CRF) controls the anterior pituitary secretion of adrenocorticotropin and other propiomelanocortin products. CRF also coordinates the endocrine, behavioral and autonomic responses to stress. The long-term objectives of this proposal are to establish that selective corticotrophin releasing factor receptor subtype 1 (CRF1) antagonists will have therapeutic implications in irritable bowel syndrome (IBS) characterized by altered bowel movement and visceral hypersensitivity. The specific aims will be: 1) to demonstrate specific tissue localization of CRF1 receptors in the colon; 2) to identify and synthesize centrally acting vs. peripherally acting high affinity CRF1 receptor nonpeptide antagonists; and 3) to examine both centrally acting and peripherally acting CRF1 antagonists in models of stress-related colonic motor stimulation and visceral hypersensitivity in rodents for potential utility in IBS. This will be achieved using novel

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tools including C-terminal CRF1 receptor antibodies, selective CRF1 receptor antagonists and experimental models to assess distal colonic motor function and visceromotor response to colorectal distension. Based on the co-morbidity between anxiety/depression and IBS and stress-related onset or enhanced IBS symptomatology, these pre-clinical studies will provide the key information needed to pursue a novel therapeutic approach for IBS using Neurocrine CRF1 receptor antagonists and to further develop this therapeutic approach in Phase II studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEX DIFFERENCES IN VISCERAL PAIN: INFLUENCE OF GONADAL STEROIDS Principal Investigator & Institution: Murhpy, Anne Z.; Univ of Maryland, Baltimore Baltimore, Md Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Irritable bowel syndrome (IBS), a common gastrointestinal disorder characterized by abdominal pain and a change in bowel habits, will affect up to 20% of the general population. Epidemiological studies have established that females are 2-5x more likely to suffer from IBS in comparison to males. A defining characteristic of IBS is severe gastrointestinal pain. Surprisingly, while an extensive body of research has been conducted examining the neural mechanisms underlying visceral pain, these studies have been conducted exclusively in males. Thus, it is not known how visceroceptive information is processed within the CNS of females. Similarly, the impact of gonadal steroids on visceral pain is also not known. Behavioral studies in Aim 1 will characterize the sex differences and influence of gonadal steroids on visceral pain. Our preliminary data indicate that there are profound sex differences in the visceral motor reflex, an indicator of visceral pain following noxious colorectal distention. Our data further show that the sexually dimorphic response to noxious visceral stimulation is estrogen dependent. Anatomical studies proposed in Aim 2 will test the hypothesis that sex differences in the organization and activation of the spinoparabrachial circuit provide the anatomical substrate for the dimorphic response to noxious visceral stimulation. Studies using acute somatic stimuli have reported that morphine produces a significantly greater degree of analgesia in males versus females, and our preliminary studies indicate that morphine alleviation of visceral pain is also sexually dimorphic. Studies proposed in Aim 3 will test the hypothesis that morphine produces a significantly greater degree of analgesia in males in comparison to females in a model of visceral pain. Immunocytochemical and molecular studies proposed in Aim 4 will test the hypothesis that opioid receptor expression within the lumbosacral spinal cord is sexually dimorphic. The influence of gonadal steroids on opioid receptor expression will also be examined. Together, these studies will begin to elucidate the neural mechanisms underlying sex differences in visceral pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLOWING OF TRANSIT - THE THIRD ENTERIC FUNCTION OF 5HT Principal Investigator & Institution: Lin, Henry C.; Director Gastrointestinal Motility Progr; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): In order to optimize nutrition, the movement of a meal through the small intestine must be precisely controlled to ensure that there is

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adequate time to complete the time-demanding steps of digestion and absorption. Abdominal pain, nausea, bloating, diarrhea and malnutrition are the consequences of impaired control of intestinal transit. After a fat-containing meal, inhibitory feedback mechanisms are activated by the proximal and distal small intestine as the jejunal and ileal brake, respectively. In contrast to this focus of the postprandial gut to slow transit, much of the research efforts over the past 100 years have been directed at the peristaltic reflex, which is responsible for the acceleration of intestinal transit and are known to be mediated by 5-HT. Currently, two roles of enteric 5-HT have been established: the triggering of the peristaltic and mucosal secretory reflexes via intrinsic primary afferent neurons and gut-to-CNS and gut-to-pancreas communications via extrinsic sensory nerves. We have recently found a third role of enteric 5-HT. Specifically, 5-HT is also involved in the slowing of transit by fat via a 5-HT3 pathway that is dependent on 5-HT transmission via myenteric neurons. In this proposal, we will test our overall hypothesis that slowing of intestinal transit by fat depends on primary afferent nerves, betaadrenergic pathway and 5-HT transmission via myenteric neurons, which in turn activates opioid neurons, that slow transit. We will test the hypotheses using pharmacologic and physiologic approaches. The results of these studies will help us to refine our hypotheses so that we can test the neuroanatomic components of this pathway using immunohistochemistry. We have developed a collaboration with 2 leading neuroscientists who will provide this project with additional expertise in immunohistochemistry. In addition, to test the role of a novel beta-adrenergic system in the slowing of intestinal transit by fat, we have developed a multi-disciplinary team approach by including a cardiologist experienced in the 13- adrenergic system. The PI has a track record of success in bench-to-bedside translational research in the area of nutrient control of intestinal transit. His experience includes the discovery of a novel, nutrient-based strategy to slow intestinal transit. This application will bring this new treatment back to basic research so that we can understand the neural pathways that underpin the slowing response to fat. The hypotheses to be tested in this project will expand our understanding of a new role for enteric 5-HT which may explain conditions such as irritable bowel syndrome and provide better understanding of the effects of drugs that are directed at 5-HT pathways. In addition, by investigating the mediators of the control of intestinal transit, we will gain knowledge that can be used to control the movement of a meal through the small intestine and, in turn, reduce symptoms and improve nutrition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPATIAL AND TEMPORAL CHARACTERISTICS OF CENTRAL PAIN SE Principal Investigator & Institution: Mauderli, Andre P.; Prosthodontics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by the applicant): Prolonged pain appears to have the potential to modulate its own intensity through positive and negative feedback (central sensitization by pain, pain inhibition by pain). If the feedback is positive, the result is a vicious pain cycle and a progressive increase in pain sensitivity. Increased pain sensitivity means that a given stimulus is perceived as more painful (hyperalgesia), or - in more extreme cases - that a previously non-painful stimulus becomes painful (allodynia). The vicious cycle may lead to sensitization beyond the topographical boundaries of the original pain, and thus it may render remote body regions more pain-prone. The result may be a snowball effect of progressive expansion of the painful area. There is evidence suggesting that the

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vicious cycle may be a pathophysiological factor in certain chronic pain diseases, including fibromyalgia syndrome (FMS), myofascial pain syndrome (MPS), and irritable bowel syndrome (IBS). This research is guided by 4 questions: 1) Does the intensity and duration of a persistent pain have an effect on how pain sensitivity changes over time? 2) Does the sensitizing effect of pain signals reach beyond the topographical location of the original pain focus? 3) Is it possible to interrupt the vicious pain cycle and allow the sensitized state to return to normal by temporarily silencing the local pain focus that presumably started the cycle? 4) Does the maintenance of the sensitized state depend on central NMDA receptor function, molecular constituents known to play a role in temporal integration of pain stimuli and other memory systems? The subjects in this study will be asked to rate pain intensities by setting the slider on an electronic visual analog scale. Novel methodology will be used for probing the temporal and spatial response properties of central pain modulation with experimental pain with prolonged series of thermal pulses. The effect of silencing clinical pain foci with transdermally delivered local anesthetics on thermallyinduced sensitization will be studied. The importance of NMDA receptor systems in the maintenance of a sensitized state will be assessed by measuring pain sensitization properties before and after pharmacologically blocking them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE FUNCTION RELATIONSHIP OF MUSCARINIC TOXIN MT-7 Principal Investigator & Institution: Baksi, Krishna; Universidad Central Del Caribe Bayamon, Pr 009606032 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-DEC-2005 Summary: Muscarinic acetylcholine receptors (mAChRs) are coupled to G-proteins and activate different second messengers and ion channels. Currently, there are five subtypes of mAChRs (M1 to M5) which are differentially distributed throughout the body. mAChRs are involved in a variety of disorders such as irritable bowel syndrome, asthma, glaucoma, cardiac arrhythmia, Parkinson's disease (PD), and Alzheimer's disease (AD). To date, the study of functions and characterization of subtypes of mAChRs are hampered due to lack of highly selective agonists and antagonists. Several toxins which recognize the mAChRs have been purified and sequenced from the venom of mamba snakes of the genus Dendroaspis. The sequences of the toxins are homologous, but their mode of action and selectivity for mAChR subtypes are different. For example, MT-7 is specific only for M1 receptors, whereas MT-3 toxin shows high affinity for M4 receptors, and low affinity for M1 receptors. The structure- activity relationship of MT-7 toxin, therefore, needed to establish the essential amino acid residues responsible for its binding to the M1 receptor to display its functions clearly. Biologically active recombinant MT-7 (rMT-7) toxin is available for such studies. The hypothesis of this proposal is that the functional site of MT-7 toxin requires multiple amino acid residues studies. The hypothesis of this proposal is that the functional site of MT-7 toxin requires multiple amino acid residues which are present in all the three loops of the toxin for its subtype specificity as well as for its action as antagonist. I, therefore propose to study the interaction of MT-7 toxin to M1 receptor, and the Specific Aims of my proposal are. SPECIFIC AIM 1: Production of MT7/MT3 chimeras and MT7M analogues. SPECIFIC AIM 2: Structure function relationship. SPECIFIC AIM 3: The mode of interaction of MT7/MT3chimeras/MT-7 analogues with M1 receptors. The completion of this study will lead us to establish the critical amino acid residues responsible for MT-7 toxin's binding to its receptor, and will also establish the specific

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amino acid residues responsible for MT-7 toxin's subtype specificity. The results will help to design therapeutic agents for different disorders involving mAChRs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE EFFICACY OF REIKI IN THE TREATMENT OF FIBROMYALGIA Principal Investigator & Institution: Assefi, Nassim P.; Women's Health Specialist; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 28-FEB-2004 Summary: (provided by applicant): Fibromyalgia (FM), one of the most common rheumatologic diagnoses, is a condition of unknown etiology characterized by widespread muscle pain and stiffness, accompanied by a variety of other symptoms including sleep disturbance, headaches, irritable bowel syndrome, and psychological distress. Treatment is generally unsatisfactory and most randomized, controlled treatment trials have been unable to demonstrate a sustained effective intervention. Thus, it is not surprising that the vast majority of FM patients have tried complementary and alternative medicine (CAM) therapies. Reiki is a form of energy medicine in which practitioners reportedly access universal life energy to heal patients, either by direct contact at specific hand positions or from a distance. A vast body of anecdotal literature as well as 2 randomized controlled trials suggest that Reiki may be an effective treatment for FM, appearing to relieve pain and improve psychological well being. In addition, it appears to have no adverse effects and can eventually be self-administered, making it a low-risk, low-cost, potentially patient-empowering intervention. This study will investigate the efficacy of Reiki in the treatment of FM. 100 Reiki-naive FM patients will be recruited from a chronic fatigue referral clinic, and will undergo an 8-week, biweekly (16 treatments) trial. Patients will be randomized into 2 Reiki groups (directcontact and distant Reiki) and 2 control (sham and placebo) groups. The sham Reiki practitioners will be professional actors who resemble the true Reiki practitioners but have no experience with health care or healing arts and are taught to mimic the Reiki Masters' verbal and physical interactions with the patients, while distracting whatever healing intention they may possess by doing mental arithmetic. The specific aims of this study are: 1) to evaluate the short and long-term efficacy and safety of an 8-week placebo-controlled randomized trial of both direct-contact and distant Reiki in the treatment of FM; 2) establish carefully constructed control groups for their feasibility and scientific usefulness for future trials of Reiki and other types of energy medicine; and 3) to collect pilot data for larger trials on the mechanism, safety, and duration of clinical and subjective effects of Reiki. Patients will be assessed at enrollment, 4 and 8 weeks during treatment and 12 weeks post-treatment. Our primary outcomes will be patient global assessment, subjective pain and mean number of tender points. Secondary outcomes will include pain threshold, sleep, fatigue, and psychological indicators. This pilot study could potentially impact the clinical care of the estimated 6 million Americans with FM, and shape the design of future larger, randomized, placebocontrolled trials of Reiki and other energy therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT OF FEAR AND PAIN IN IRRITABLE BOWEL SYNDROMEN Principal Investigator & Institution: Naliboff, Bruce D.; Clinical Professor; Brentwood Biomedical Research Institute Bldg. 114, Room 218 Los Angeles, Ca 90073 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-MAY-2007

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Summary: (provided by applicant) Irritable Bowel Syndrome (IBS) is the most common of the functional gastrointestinal disorders with primary symptoms of chronic abdominal pain or discomfort associated with altered bowel habits. IBS is characterized by stress-related symptom exacerbations and a high co-morbidity with affective disorders, in particular, anxiety. The current proposal is based on a disease model of IBS that emphasizes enhanced responsiveness and conditioning of stress and fear circuits in the central nervous system, and associated hypervigilance, stress-induced hyperalgesia, and altered autonomic responses to visceral sensation. Based on this model and the highly successful exposure treatments now used for anxiety disorders, we have designed and successfully piloted a unique cognitive behavioral treatment (CBT) for IBS. Traditional CBT treatments focus on decreasing general stress responses and increasing coping skills for life stress, and have shown only modest efficacy in IBS. We hypothesize that IBS symptoms can be more effectively treated by specifically changing responses to visceral sensations through decreasing interoceptive conditioned responses, and directing attention away from visceral stimuli. If our hypotheses are correct, we expect to see greater symptom improvements as well as normalization of altered physiological responses following this new CBT approach. We propose to address the following specific aims: 1) Do subjective outcomes differ between the two cognitive behavioral interventions with and without interoceptive exposure and directed attention, and an attention control treatment? 2) Are differential treatment responses accompanied by changes in perceptual and autonomic responses to visceral stimuli? And 3) Are differential treatment responses accompanied by normalization of altered regional brain activation in response to visceral stimuli? In separate studies we will compare CBT with interoceptive exposure and directed attention to tradition CBT (and a control condition) on outcome measures of symptom reduction, beliefs, visceral sensitivity (pain, discomfort, and fear responses to balloon distension), and central responses to visceral stimulation using functional magnetic resonance imaging (fMRI). 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

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approaches to functional brain imaging techniques will be used to address the following specific aims in the four Projects: 1. Sex Differences in Central Stress Circuit Responsiveness in IBS and IC patients 2. Sex differences in the colonic responses to stress: Role of CRF pathways 3. Sex differences in neuroendocrine and immunologic responses in IBS 4. Sex differences in CRF, noradrenergic function and oxytocin in cats with IC. To facilitate the research, the Center has an Administrative Core and a Scientific Core (Neuroendocrine Measures) and will take advantage of existing NIH-funded core and service facilities on campus, including the CURE: Digestive Diseases Research Center, the UCLA Brain Mapping Center and the GCRC. The Center provides an optimal environment for cooperation and collaboration among its investigators, who already have had a major impact on the field individually. Thus, the synergy expected from the Center promises to have an even larger impact upon expanded research into a highly prevalent, but inadequately treated area of women's health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

Do published guidelines for evaluation of Irritable Bowel Syndrome reflect practice? by Yawn BP, Lydick E, Locke GR, Wollan PC, Bertram SL, Kurland MJ.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59674

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Increased risk of irritable bowel syndrome after bacterial gastroenteritis: cohort study. by Rodriguez LA, Ruigomez A.; 1999 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27756

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Irritable bowel syndrome: Could it be celiac disease? by Hoey J.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99362

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6

3 4

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

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

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

A population study on irritable bowel syndrome and mental health. Author(s): Osterberg E, Blomquist L, Krakau I, Weinryb RM, Asberg M, Hultcrantz R. Source: Scandinavian Journal of Gastroenterology. 2000 March; 35(3): 264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766319&dopt=Abstract

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A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Author(s): Kim HJ, Camilleri M, McKinzie S, Lempke MB, Burton DD, Thomforde GM, Zinsmeister AR. Source: Alimentary Pharmacology & Therapeutics. 2003 April 1; 17(7): 895-904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656692&dopt=Abstract

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A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome. Author(s): Boyce PM, Talley NJ, Balaam B, Koloski NA, Truman G. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14572570&dopt=Abstract

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A systematic review of tegaserod for the treatment of irritable bowel syndrome. Author(s): Bergmann K. Source: Journal of Clinical Pharmacy and Therapeutics. 2003 April; 28(2): 151-3; Author Reply 153. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713613&dopt=Abstract

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Abnormalities of left colonic motility in ambulant nonconstipated patients with irritable bowel syndrome. Author(s): Clemens CH, Samsom M, Van Berge Henegouwen GP, Smout AJ. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 74-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645793&dopt=Abstract

journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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Abuse, dissociation, and somatization in irritable bowel syndrome: towards an explanatory model. Author(s): Salmon P, Skaife K, Rhodes J. Source: Journal of Behavioral Medicine. 2003 February; 26(1): 1-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690943&dopt=Abstract

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Alosetron approved for treatment of irritable bowel syndrome. Author(s): Miller JL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 March 15; 57(6): 519. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10754758&dopt=Abstract

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Alosetron in irritable bowel syndrome. Author(s): McColl KE. Source: Lancet. 2000 July 8; 356(9224): 164-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10963271&dopt=Abstract

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Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Author(s): Jones RH, Holtmann G, Rodrigo L, Ehsanullah RS, Crompton PM, Jacques LA, Mills JG. Source: Alimentary Pharmacology & Therapeutics. 1999 November; 13(11): 1419-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10571597&dopt=Abstract

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Alosetron, a 5-HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers. Author(s): Houghton LA, Foster JM, Whorwell PJ. Source: Alimentary Pharmacology & Therapeutics. 2000 June; 14(6): 775-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10848662&dopt=Abstract

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Alosetron: a new therapy for irritable bowel syndrome. Author(s): Kupecz D. Source: The Nurse Practitioner. 2000 July; 25(7): 95-6, 98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10916831&dopt=Abstract

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Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Author(s): Nobaek S, Johansson ML, Molin G, Ahrne S, Jeppsson B. Source: The American Journal of Gastroenterology. 2000 May; 95(5): 1231-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10811333&dopt=Abstract

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An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Author(s): Kellow J, Lee OY, Chang FY, Thongsawat S, Mazlam MZ, Yuen H, Gwee KA, Bak YT, Jones J, Wagner A. Source: Gut. 2003 May; 52(5): 671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692051&dopt=Abstract

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Anal pressure waves in patients with irritable bowel syndrome. Author(s): Bouchoucha M, Choufa T, Faye A, Berger A, Arsac M. Source: Diseases of the Colon and Rectum. 1999 November; 42(11): 1487-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566540&dopt=Abstract

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Anisocoria associated with the medical treatment of irritable bowel syndrome. Author(s): Nussdorf JD, Berman EL. Source: Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. 2000 June; 20(2): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870922&dopt=Abstract

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Anxiety and depression are related to autonomic nervous system function in women with irritable bowel syndrome. Author(s): Jarrett ME, Burr RL, Cain KC, Hertig V, Weisman P, Heitkemper MM. Source: Digestive Diseases and Sciences. 2003 February; 48(2): 386-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643620&dopt=Abstract

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Are probiotics useful in irritable bowel syndrome? Author(s): Faber SM. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811225&dopt=Abstract

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Arrowroot as a treatment for diarrhoea in irritable bowel syndrome patients: a pilot study. Author(s): Cooke C, Carr I, Abrams K, Mayberry J. Source: Arquivos De Gastroenterologia. 2000 January-March; 37(1): 20-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962623&dopt=Abstract

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Association between pain episodes and high amplitude propagated pressure waves in patients with irritable bowel syndrome. Author(s): Clemens CH, Samsom M, Roelofs JM, van Berge Henegouwen GP, Smout AJ. Source: The American Journal of Gastroenterology. 2003 August; 98(8): 1838-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907341&dopt=Abstract

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Autonomic nervous system reactivity in irritable bowel syndrome. Author(s): Punyabati O, Deepak KK, Sharma MP, Dwivedi SN. Source: Indian J Gastroenterol. 2000 July-September; 19(3): 122-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918719&dopt=Abstract

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Bacterial supplementation in the irritable bowel syndrome. A randomised doubleblind placebo-controlled crossover study. Author(s): O'Sullivan MA, O'Morain CA. Source: Dig Liver Dis. 2000 May; 32(4): 294-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515626&dopt=Abstract

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Basic pathophysiologic mechanisms in irritable bowel syndrome. Author(s): Mayer EA, Naliboff BD, Chang L. Source: Digestive Diseases (Basel, Switzerland). 2001; 19(3): 212-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752839&dopt=Abstract

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Behavioral and physiological sleep characteristics in women with irritable bowel syndrome. Author(s): Elsenbruch S, Thompson JJ, Hamish MJ, Exton MS, Orr WC. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2306-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358249&dopt=Abstract

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Behavioral treatment of irritable bowel syndrome: a 1-year follow-up study. Author(s): Schwarz SP, Blanchard EB, Neff DF. Source: Biofeedback Self Regul. 1986 September; 11(3): 189-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3300787&dopt=Abstract

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Behaviorally treated irritable bowel syndrome patients: a four-year follow-up. Author(s): Schwarz SP, Taylor AE, Scharff L, Blanchard EB. Source: Behaviour Research and Therapy. 1990; 28(4): 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2222390&dopt=Abstract

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Behavioural psychotherapy in the treatment of irritable bowel syndrome. Author(s): Corney RH, Stanton R, Newell R, Clare A, Fairclough P. Source: Journal of Psychosomatic Research. 1991; 35(4-5): 461-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1920177&dopt=Abstract

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Bladder dysfunction and irritable bowel syndrome. Author(s): Terruzzi V, Magatti F, Quadri G, Tenore C, Minoli G, Belloni C. Source: The American Journal of Gastroenterology. 1992 September; 87(9): 1231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1519598&dopt=Abstract

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Bladder smooth muscle dysfunction in patients with irritable bowel syndrome. Author(s): Whorwell PJ, Lupton EW, Erduran D, Wilson K. Source: Gut. 1986 September; 27(9): 1014-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3758813&dopt=Abstract

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Bowel dysfunction and irritable bowel syndrome in fibromyalgia patients. Author(s): Sivri A, Cindas A, Dincer F, Sivri B. Source: Clinical Rheumatology. 1996 May; 15(3): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793261&dopt=Abstract

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Bowel sound biofeedback as a treatment for irritable bowel syndrome. Author(s): Radnitz CL, Blanchard EB. Source: Biofeedback Self Regul. 1988 June; 13(2): 169-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3207766&dopt=Abstract

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Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Author(s): McEvoy R. Source: The Medical Journal of Australia. 1989 July 17; 151(2): 112. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2783226&dopt=Abstract

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Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Author(s): Borody TJ, George L, Andrews P, Brandl S, Noonan S, Cole P, Hyland L, Morgan A, Maysey J, Moore-Jones D. Source: The Medical Journal of Australia. 1989 May 15; 150(10): 604. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2783214&dopt=Abstract

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Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia. Author(s): Chang L, Berman S, Mayer EA, Suyenobu B, Derbyshire S, Naliboff B, Vogt B, FitzGerald L, Mandelkern MA. Source: The American Journal of Gastroenterology. 2003 June; 98(6): 1354-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818281&dopt=Abstract

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Brain-gut interaction in irritable bowel syndrome. Author(s): Harris ML, Aziz Q. Source: Hosp Med. 2003 May; 64(5): 264-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789734&dopt=Abstract

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Brain-gut interaction in irritable bowel syndrome: new findings of a multicomponent disease model. Author(s): Schmulson MJ. Source: Isr Med Assoc J. 2001 February; 3(2): 104-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347592&dopt=Abstract

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Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome. A preliminary study. Author(s): Fukudo S, Nomura T, Muranaka M, Taguchi F. Source: Journal of Clinical Gastroenterology. 1993 September; 17(2): 133-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8031340&dopt=Abstract

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Bran and irritable bowel syndrome: time for reappraisal. Author(s): Francis CY, Whorwell PJ. Source: Lancet. 1994 July 2; 344(8914): 39-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7912305&dopt=Abstract

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Bran supplementation in the treatment of irritable bowel syndrome. Author(s): Snook J, Shepherd HA. Source: Alimentary Pharmacology & Therapeutics. 1994 October; 8(5): 511-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7865643&dopt=Abstract

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British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome. Author(s): Jones J, Boorman J, Cann P, Forbes A, Gomborone J, Heaton K, Hungin P, Kumar D, Libby G, Spiller R, Read N, Silk D, Whorwell P. Source: Gut. 2000 November; 47 Suppl 2: Ii1-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053260&dopt=Abstract

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Burden of illness in irritable bowel syndrome comparing Rome I and Rome II criteria. Author(s): Badia X, Mearin F, Balboa A, Baro E, Caldwell E, Cucala M, Diaz-Rubio M, Fueyo A, Ponce J, Roset M, Talley NJ. Source: Pharmacoeconomics. 2002; 20(11): 749-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201794&dopt=Abstract

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Celiac sprue as a possible cause of symptoms in presumed irritable bowel syndrome. Author(s): Hasler WL. Source: Gastroenterology. 2002 June; 122(7): 2086-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078669&dopt=Abstract

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Central processing of rectal pain in patients with irritable bowel syndrome: an fMRI study. Author(s): Bonaz B, Baciu M, Papillon E, Bost R, Gueddah N, Le Bas JF, Fournet J, Segebarth C. Source: The American Journal of Gastroenterology. 2002 March; 97(3): 654-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926209&dopt=Abstract

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Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome. Author(s): Verne GN, Himes NC, Robinson ME, Gopinath KS, Briggs RW, Crosson B, Price DD. Source: Pain. 2003 May; 103(1-2): 99-110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749964&dopt=Abstract

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Cerebral response to electric stimulation of the colon and abdominal skin in healthy subjects and patients with irritable bowel syndrome. Author(s): Rossel P, Pedersen P, Niddam D, Arendt-Nielsen L, Chen AC, Drewes AM. Source: Scandinavian Journal of Gastroenterology. 2001 December; 36(12): 1259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11761014&dopt=Abstract

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Charcoal tablets in the treatment of patients with irritable bowel syndrome. Author(s): Hubner WD, Moser EH. Source: Adv Ther. 2002 September-October; 19(5): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12539884&dopt=Abstract

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Childhood recurrent abdominal pain and subsequent adult irritable bowel syndrome. Author(s): Hyams JS, Hyman PE, Rasquin-Weber A. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 1999 October; 20(5): 318-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10533988&dopt=Abstract

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Chili pepper and rectal hyperalgesia in irritable bowel syndrome. Author(s): Schmulson MJ, Valdovinos MA, Milke P. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1214-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809862&dopt=Abstract

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Chronic pelvic pain and irritable bowel syndrome. Author(s): Gupta JK, More S, Clark TJ. Source: Hosp Med. 2003 May; 64(5): 275-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789736&dopt=Abstract

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Clinical assessment of irritable bowel syndrome. Author(s): Lembo TJ, Fink RN. Source: Journal of Clinical Gastroenterology. 2002 July; 35(1 Suppl): S31-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184137&dopt=Abstract

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Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome. Author(s): Camilleri M, Heading RC, Thompson WG. Source: Alimentary Pharmacology & Therapeutics. 2002 August; 16(8): 1407-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182741&dopt=Abstract

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Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome. Author(s): Corazziari E, Bytzer P, Delvaux M, Holtmann G, Malagelada JR, Morris J, Muller-Lissner S, Spiller RC, Tack J, Whorwell PJ. Source: Alimentary Pharmacology & Therapeutics. 2003 September 15; 18(6): 569-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969083&dopt=Abstract

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Coeliac disease presenting with symptoms of irritable bowel syndrome. Author(s): Shahbazkhani B, Forootan M, Merat S, Akbari MR, Nasserimoghadam S, Vahedi H, Malekzadeh R. Source: Alimentary Pharmacology & Therapeutics. 2003 July 15; 18(2): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869084&dopt=Abstract

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Cognitive function in people with chronic illness: inflammatory bowel disease and irritable bowel syndrome. Author(s): Attree EA, Dancey CP, Keeling D, Wilson C. Source: Applied Neuropsychology. 2003; 10(2): 96-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788684&dopt=Abstract

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Cognitive-behaviour therapy as a treatment for irritable bowel syndrome: a pilot study. Author(s): Boyce P, Gilchrist J, Talley NJ, Rose D. Source: The Australian and New Zealand Journal of Psychiatry. 2000 April; 34(2): 300-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789535&dopt=Abstract

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Comorbidity of irritable bowel syndrome in psychiatric patients: a review. Author(s): Garakani A, Win T, Virk S, Gupta S, Kaplan D, Masand PS. Source: American Journal of Therapeutics. 2003 January-February; 10(1): 61-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522523&dopt=Abstract

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Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome. Author(s): Steens J, Van Der Schaar PJ, Penning C, Brussee J, Masclee AA. Source: Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. 2002 June; 14(3): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12061908&dopt=Abstract

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Contemporary thoughts on the treatment of irritable bowel syndrome. Author(s): Giaquinta D. Source: Manag Care Interface. 2002 August; 15(8): 19-20, 22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12229060&dopt=Abstract

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Correlation of serotonin and monoamine oxidase levels with anxiety level in diarrhea-predominant irritable bowel syndrome. Author(s): Singh RK, Pandey HP, Singh RH. Source: Indian J Gastroenterol. 2003 May-June; 22(3): 88-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839379&dopt=Abstract

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Current concepts of the irritable bowel syndrome. Author(s): Quigley EM. Source: Scandinavian Journal of Gastroenterology. Supplement. 2003; (237): 1-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797672&dopt=Abstract

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Current insights into the pathophysiology of irritable bowel syndrome. Author(s): Schwetz I, Bradesi S, Mayer EA. Source: Current Gastroenterology Reports. 2003 August; 5(4): 331-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864964&dopt=Abstract

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Dealing with irritable bowel syndrome. Author(s): Abbas Z. Source: J Pak Med Assoc. 1999 March; 49(3): 78-81 Concl. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10531788&dopt=Abstract

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Defining and diagnosing irritable bowel syndrome. Author(s): Schuster MM. Source: Am J Manag Care. 2001 July; 7(8 Suppl): S246-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474909&dopt=Abstract

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Detection of colorectal tumor and inflammatory bowel disease during follow-up of patients with initial diagnosis of irritable bowel syndrome. Author(s): Garcia Rodriguez LA, Ruigomez A, Wallander MA, Johansson S, Olbe L. Source: Scandinavian Journal of Gastroenterology. 2000 March; 35(3): 306-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766326&dopt=Abstract

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Diagnosing irritable bowel syndrome. Author(s): van Zanten SV. Source: Reviews in Gastroenterological Disorders. 2003; 3 Suppl 2: S12-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775998&dopt=Abstract

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Diagnosing the patient with abdominal pain and altered bowel habits: is it irritable bowel syndrome? Author(s): Holten KB, Wetherington A, Bankston L. Source: American Family Physician. 2003 May 15; 67(10): 2157-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776965&dopt=Abstract

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Diagnosis of irritable bowel syndrome. Author(s): Olden KW. Source: Gastroenterology. 2002 May; 122(6): 1701-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016433&dopt=Abstract

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Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Author(s): Carroccio A, Iacono G, Cottone M, Di Prima L, Cartabellotta F, Cavataio F, Scalici C, Montalto G, Di Fede G, Rini G, Notarbartolo A, Averna MR. Source: Clinical Chemistry. 2003 June; 49(6 Pt 1): 861-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765980&dopt=Abstract

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Diet in the irritable bowel syndrome. Author(s): Floch MH, Narayan R. Source: Journal of Clinical Gastroenterology. 2002 July; 35(1 Suppl): S45-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184139&dopt=Abstract

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Diet triggers symptoms in women with irritable bowel syndrome. The patient's perspective. Author(s): Jarrett M, Visser R, Heitkemper M. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2001 September-October; 24(5): 246-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847996&dopt=Abstract

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Direct clinical evidence for spinal hyperalgesia in a patient with irritable bowel syndrome. Author(s): Malcolm A, Phillips SF, Kellow JE, Cousins MJ. Source: The American Journal of Gastroenterology. 2001 August; 96(8): 2427-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513185&dopt=Abstract

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Distal colonic motor activity in four subgroups of patients with irritable bowel syndrome. Author(s): Cole SJ, Duncan HD, Claydon AH, Austin D, Bowling TE, Silk DB. Source: Digestive Diseases and Sciences. 2002 February; 47(2): 345-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858232&dopt=Abstract

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Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome. Author(s): Dunlop SP, Jenkins D, Spiller RC. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1578-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873581&dopt=Abstract

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Division of the irritable bowel syndrome into subgroups on the basis of daily recorded symptoms in two outpatients samples. Author(s): Ragnarsson G, Bodemar G. Source: Scandinavian Journal of Gastroenterology. 1999 October; 34(10): 993-1000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563669&dopt=Abstract

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Do published guidelines for evaluation of irritable bowel syndrome reflect practice? Author(s): Yawn BP, Lydick E, Locke GR, Wollan PC, Bertram SL, Kurland MJ. Source: Bmc Gastroenterology [electronic Resource]. 2001; 1(1): 11. Epub 2001 October 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11701092&dopt=Abstract

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Does a physically active lifestyle improve symptoms in women with irritable bowel syndrome? Author(s): Lustyk MK, Jarrett ME, Bennett JC, Heitkemper MM. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2001 May-June; 24(3): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847862&dopt=Abstract

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Does a preexisting anxiety disorder predict response to paroxetine in irritable bowel syndrome? Author(s): Masand PS, Gupta S, Schwartz TL, Kaplan D, Virk S, Hameed A, Lockwood K. Source: Psychosomatics. 2002 November-December; 43(6): 451-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444227&dopt=Abstract

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Does irritable bowel syndrome really exist? Reactions to the proposed motility-based classification system. Author(s): Whitehead WE. Source: Gastroenterology. 2003 March; 124(3): 598. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612895&dopt=Abstract

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Drug therapy options for patients with irritable bowel syndrome. Author(s): Talley NJ. Source: Am J Manag Care. 2001 July; 7(8 Suppl): S261-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474911&dopt=Abstract

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Dyspepsia, irritable bowel syndrome, and constipation: review and what's new. Author(s): Camilleri M. Source: Reviews in Gastroenterological Disorders. 2001; 1(1): 2-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120117&dopt=Abstract

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Dyspeptic symptoms and gastric emptying in the irritable bowel syndrome. Author(s): Stanghellini V, Tosetti C, Barbara G, De Giorgio R, Cogliandro L, Cogliandro R, Corinaldesi R. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2738-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425541&dopt=Abstract

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Economic burden of irritable bowel syndrome. Proposed strategies to control expenditures. Author(s): Camilleri M, Williams DE. Source: Pharmacoeconomics. 2000 April; 17(4): 331-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947488&dopt=Abstract

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Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers. Author(s): Clemens CH, Samsom M, Van Berge Henegouwen GP, Fabri M, Smout AJ. Source: Alimentary Pharmacology & Therapeutics. 2002 May; 16(5): 993-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966509&dopt=Abstract

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Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of irritable bowel syndrome. Author(s): Sen S, Mullan MM, Parker TJ, Woolner JT, Tarry SA, Hunter JO. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2615-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452404&dopt=Abstract

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Effect of red chillies on small bowel and colonic transit and rectal sensitivity in men with irritable bowel syndrome. Author(s): Agarwal MK, Bhatia SJ, Desai SA, Bhure U, Melgiri S. Source: Indian J Gastroenterol. 2002 September-October; 21(5): 179-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416746&dopt=Abstract

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Effects of alosetron on gastrointestinal transit time and rectal sensation in patients with irritable bowel syndrome. Author(s): Thumshirn M, Coulie B, Camilleri M, Zinsmeister AR, Burton DD, Van Dyke C. Source: Alimentary Pharmacology & Therapeutics. 2000 July; 14(7): 869-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10886042&dopt=Abstract

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Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Author(s): Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW. Source: Lancet. 2000 March 25; 355(9209): 1035-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10744088&dopt=Abstract

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Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials. Author(s): Cremonini F, Delgado-Aros S, Camilleri M. Source: Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. 2003 February; 15(1): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588472&dopt=Abstract

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Efficacy of trimebutine therapy in patients with gastroesophageal reflux disease and irritable bowel syndrome. Author(s): Kountouras J, Chatzopoulos D, Zavos C, Boura P, Venizelos J, Kalis A. Source: Hepatogastroenterology. 2002 January-February; 49(43): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11941952&dopt=Abstract

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Enhanced preattentive central nervous system reactivity in irritable bowel syndrome. Author(s): Berman SM, Naliboff BD, Chang L, Fitzgerald L, Antolin T, Camplone A, Mayer EA. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2791-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425550&dopt=Abstract

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Epidemiology of irritable bowel syndrome in Chinese. Author(s): Lau EM, Chan FK, Ziea ET, Chan CS, Wu JC, Sung JJ. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2621-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452405&dopt=Abstract

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Epidemiology of irritable bowel syndrome in Croatia. Author(s): Baretic M, Bilic A, Jurcic D, Mihanovic M, Sunic-Omejc M, Dorosulic Z, Restek-Petrovic B. Source: Coll Antropol. 2002 December; 26 Suppl: 85-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674839&dopt=Abstract

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Evaluation of drug treatment in irritable bowel syndrome. Author(s): Talley NJ. Source: British Journal of Clinical Pharmacology. 2003 October; 56(4): 362-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968980&dopt=Abstract

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Evaluation of hydrogen excretion after lactulose administration as a screening test for causes of irritable bowel syndrome. Author(s): Sen S, Dear KL, King TS, Elia M, Hunter JO. Source: European Journal of Gastroenterology & Hepatology. 2002 July; 14(7): 753-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169984&dopt=Abstract

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Evidence for autonomic dysregulation in the irritable bowel syndrome. Author(s): Gupta V, Sheffield D, Verne GN. Source: Digestive Diseases and Sciences. 2002 August; 47(8): 1716-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184520&dopt=Abstract

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Evidence-based position statement on the management of irritable bowel syndrome in North America. Author(s): American College of Gastroenterology Functional Gastrointestinal Disorders Task Froce. Source: The American Journal of Gastroenterology. 2002 November; 97(11 Suppl): S1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425585&dopt=Abstract

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Evolution of visceral sensitivity in patients with irritable bowel syndrome. Author(s): Poitras P, Riberdy Poitras M, Plourde V, Boivin M, Verrier P. Source: Digestive Diseases and Sciences. 2002 April; 47(4): 914-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991628&dopt=Abstract

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Exaggerated motility of the descending colon with repetitive distention of the sigmoid colon in patients with irritable bowel syndrome. Author(s): Fukudo S, Kanazawa M, Kano M, Sagami Y, Endo Y, Utsumi A, Nomura T, Hongo M. Source: Journal of Gastroenterology. 2002 November; 37 Suppl 14: 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572883&dopt=Abstract

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Extended analysis of a double-blind, placebo-controlled, 15-week study with otilonium bromide in irritable bowel syndrome. Author(s): Glende M, Morselli-Labate AM, Battaglia G, Evangelista S. Source: European Journal of Gastroenterology & Hepatology. 2002 December; 14(12): 1331-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468954&dopt=Abstract

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Extra-intestinal manifestations associated with irritable bowel syndrome: a twin study. Author(s): Svedberg P, Johansson S, Wallander MA, Hamelin B, Pedersen NL. Source: Alimentary Pharmacology & Therapeutics. 2002 May; 16(5): 975-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966507&dopt=Abstract

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Extraintestinal symptoms in irritable bowel syndrome and inflammatory bowel diseases: nature, severity, and relationship to gastrointestinal symptoms. Author(s): Zimmerman J. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 743-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741465&dopt=Abstract

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FDA OK's two drugs for irritable bowel syndrome. The arsenal of IBS drugs is growing, but diagnosis is tricky. Author(s): Horwitz BJ. Source: Health News. 2002 October; 8(10): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416480&dopt=Abstract

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Features of eating disorders in patients with irritable bowel syndrome. Author(s): Tang TN, Toner BB, Stuckless N, Dion KL, Kaplan AS, Ali A. Source: Journal of Psychosomatic Research. 1998 August; 45(2): 171-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9753389&dopt=Abstract

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Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation. Author(s): Treem WR, Ahsan N, Kastoff G, Hyams JS. Source: Journal of Pediatric Gastroenterology and Nutrition. 1996 October; 23(3): 280-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8890079&dopt=Abstract

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Fiber supplements for irritable bowel syndrome: do they really make a difference? Author(s): Wald A. Source: The American Journal of Gastroenterology. 1990 December; 85(12): 1652-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2174644&dopt=Abstract

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Fibromyalgia in patients with irritable bowel syndrome. An association with the severity of the intestinal disorder. Author(s): Lubrano E, Iovino P, Tremolaterra F, Parsons WJ, Ciacci C, Mazzacca G. Source: International Journal of Colorectal Disease. 2001 August; 16(4): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515679&dopt=Abstract

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Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Author(s): Sperber AD, Atzmon Y, Neumann L, Weisberg I, Shalit Y, Abu-Shakrah M, Fich A, Buskila D. Source: The American Journal of Gastroenterology. 1999 December; 94(12): 3541-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606316&dopt=Abstract

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Food allergy and irritable bowel syndrome. Author(s): Mullin GE. Source: Jama : the Journal of the American Medical Association. 1991 April 3; 265(13): 1736. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2002578&dopt=Abstract

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Food allergy and the irritable bowel syndrome. Author(s): Zwetchkenbaum JF, Burakoff R. Source: The American Journal of Gastroenterology. 1988 September; 83(9): 901-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3046334&dopt=Abstract

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Food hypersensitivity and the irritable bowel syndrome. Author(s): Schmidt M, Floch MH. Source: The American Journal of Gastroenterology. 1992 January; 87(1): 18-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1728118&dopt=Abstract

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Food intolerance and the irritable bowel syndrome. Author(s): Nanda R, James R, Smith H, Dudley CR, Jewell DP. Source: Gut. 1989 August; 30(8): 1099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2767507&dopt=Abstract

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Food intolerance, atopy, and irritable bowel syndrome. Author(s): Smith MA, Youngs GR, Finn R. Source: Lancet. 1985 November 9; 2(8463): 1064. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2865536&dopt=Abstract

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Food-related gastrointestinal symptoms in the irritable bowel syndrome. Author(s): Simren M, Mansson A, Langkilde AM, Svedlund J, Abrahamsson H, Bengtsson U, Bjornsson ES. Source: Digestion. 2001; 63(2): 108-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244249&dopt=Abstract

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Fructose malabsorption and the irritable bowel syndrome. Author(s): Born P, Vierling T, Barina W. Source: Gastroenterology. 1991 November; 101(5): 1454. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1796960&dopt=Abstract

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Fructose-sorbitol malabsorption and symptom provocation in irritable bowel syndrome: relationship to enteric hypersensitivity and dysmotility. Author(s): Evans PR, Piesse C, Bak YT, Kellow JE. Source: Scandinavian Journal of Gastroenterology. 1998 November; 33(11): 1158-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9867093&dopt=Abstract

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Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Author(s): Tornblom H, Lindberg G, Nyberg B, Veress B. Source: Gastroenterology. 2002 December; 123(6): 1972-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454854&dopt=Abstract

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Functional brain imaging in irritable bowel syndrome with rectal balloon-distention by using fMRI. Author(s): Yuan YZ, Tao RJ, Xu B, Sun J, Chen KM, Miao F, Zhang ZW, Xu JY. Source: World Journal of Gastroenterology : Wjg. 2003 June; 9(6): 1356-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800256&dopt=Abstract

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Functional diagnostic work-up in patients with irritable bowel syndrome. Author(s): Klauser AG, Voderholzer WA, Schindlbeck NE, Muller-Lissner SA. Source: Zeitschrift Fur Gastroenterologie. 1996 May; 34(5): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8686358&dopt=Abstract

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Functional disability in adolescents and young adults with symptoms of irritable bowel syndrome: the role of academic, social, and athletic competence. Author(s): Claar RL, Walker LS, Smith CA. Source: Journal of Pediatric Psychology. 1999 June; 24(3): 271-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10379142&dopt=Abstract

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Functional dyspepsia and irritable bowel syndrome: is there a common pathophysiological basis? Author(s): Holtmann G, Goebell H, Talley NJ. Source: The American Journal of Gastroenterology. 1997 June; 92(6): 954-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9177509&dopt=Abstract

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Gallbladder contraction in patients with irritable bowel syndrome. Author(s): Braverman DZ. Source: Isr J Med Sci. 1987 March; 23(3): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3294738&dopt=Abstract

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Gallbladder dynamics in patients with irritable bowel syndrome and essential dyspepsia. Author(s): Misra SP, Dwivedi M, Mital M, Misra V. Source: Journal of Clinical Gastroenterology. 1991 February; 13(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2007748&dopt=Abstract

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Gallbladder function in the irritable bowel syndrome. Author(s): Keshavarziam A, Anagnostides A, Chadwick VS, Fitzpatrick ML. Source: Journal of Clinical Gastroenterology. 1987 June; 9(3): 366. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3611697&dopt=Abstract

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Gastric emptying and dyspeptic symptoms in the irritable bowel syndrome. Author(s): van Wijk HJ, Smout AJ, Akkermans LM, Roelofs JM, ten Thije OJ. Source: Scandinavian Journal of Gastroenterology. 1992; 27(2): 99-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1561533&dopt=Abstract

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Gastrointestinal dysfunction in a community sample of subjects with symptoms of irritable bowel syndrome. Author(s): Lanng C, Mortensen D, Friis M, Wallin L, Kay L, Boesby S, Jorgensen T. Source: Digestion. 2003; 67(1-2): 14-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743435&dopt=Abstract

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Gastrointestinal motility in patients with irritable bowel syndrome studied by using radiopaque markers. Author(s): Horikawa Y, Mieno H, Inoue M, Kajiyama G. Source: Scandinavian Journal of Gastroenterology. 1999 December; 34(12): 1190-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10636065&dopt=Abstract

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Gastroparesis and small bowel dysmotility in irritable bowel syndrome. Author(s): Evans PR, Bak YT, Shuter B, Hoschl R, Kellow JE. Source: Digestive Diseases and Sciences. 1997 October; 42(10): 2087-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9365140&dopt=Abstract

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Gender differences in irritable bowel syndrome. Author(s): Chang L, Heitkemper MM. Source: Gastroenterology. 2002 November; 123(5): 1686-701. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404243&dopt=Abstract

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Gender differences in irritable bowel syndrome. Author(s): Chial HJ, Camilleri M. Source: J Gend Specif Med. 2002 May-June; 5(3): 37-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078061&dopt=Abstract

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Gender differences in Manning criteria in the irritable bowel syndrome. Author(s): Smith RC, Greenbaum DS, Vancouver JB, Henry RC, Reinhart MA, Greenbaum RB, Dean HA, Mayle JE. Source: Gastroenterology. 1991 March; 100(3): 591-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1993482&dopt=Abstract

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Gender differences in psychological distress among patients with irritable bowel syndrome. Author(s): Blanchard EB, Keefer L, Galovski TE, Taylor AE, Turner SM. Source: Journal of Psychosomatic Research. 2001 May; 50(5): 271-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399285&dopt=Abstract

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Gender issues in the management of inflammatory bowel disease and irritable bowel syndrome. Author(s): Kane S. Source: Int J Fertil Womens Med. 2002 May-June; 47(3): 136-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081259&dopt=Abstract

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Gender role and irritable bowel syndrome: literature review and hypothesis. Author(s): Toner BB, Akman D. Source: The American Journal of Gastroenterology. 2000 January; 95(1): 11-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638553&dopt=Abstract

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Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome. Author(s): Viramontes BE, Camilleri M, McKinzie S, Pardi DS, Burton D, Thomforde GM. Source: The American Journal of Gastroenterology. 2001 September; 96(9): 2671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569693&dopt=Abstract

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Giardia lamblia infections become clinically evident by eliciting symptoms of irritable bowel syndrome. Author(s): D'Anchino M, Orlando D, De Feudis L. Source: The Journal of Infection. 2002 October; 45(3): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387773&dopt=Abstract

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Group treatment of patients with irritable bowel syndrome. Author(s): Lammert M, Ratner M. Source: Social Work in Health Care. 1986 Fall; 12(1): 67-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3603327&dopt=Abstract

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GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Author(s): Svedlund J, Sjodin I, Dotevall G. Source: Digestive Diseases and Sciences. 1988 February; 33(2): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3123181&dopt=Abstract

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Gut feelings about irritable bowel syndrome. Author(s): Stahl SM. Source: The Journal of Clinical Psychiatry. 2001 August; 62(8): 590-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561928&dopt=Abstract

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Gut-focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome. Author(s): Lea R, Houghton LA, Calvert EL, Larder S, Gonsalkorale WM, Whelan V, Randles J, Cooper P, Cruickshanks P, Miller V, Whorwell PJ. Source: Alimentary Pharmacology & Therapeutics. 2003 March 1; 17(5): 635-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641511&dopt=Abstract

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Gynaecological consultation in patients with the irritable bowel syndrome. Author(s): Prior A, Whorwell PJ. Source: Gut. 1989 July; 30(7): 996-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2759494&dopt=Abstract

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H. pylori infection and visceral hypersensitivity in patients with irritable bowel syndrome. Author(s): Gerards C, Leodolter A, Glasbrenner B, Malfertheiner P. Source: Digestive Diseases (Basel, Switzerland). 2001; 19(2): 170-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549828&dopt=Abstract

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Harnessing the patient's powers of recovery: the role of the psychotherapies in the irritable bowel syndrome. Author(s): Read NW. Source: Bailliere's Best Practice & Research. Clinical Gastroenterology. 1999 October; 13(3): 473-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580923&dopt=Abstract

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Health care utilization and economic issues in irritable bowel syndrome. Author(s): Gralnek IM. Source: Eur J Surg Suppl. 1998; (583): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10027677&dopt=Abstract

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Health-related quality of life among persons with irritable bowel syndrome: a systematic review. Author(s): El-Serag HB, Olden K, Bjorkman D. Source: Alimentary Pharmacology & Therapeutics. 2002 June; 16(6): 1171-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030961&dopt=Abstract

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Health-related quality of life and associated psychosocial factors in irritable bowel syndrome: a review. Author(s): Luscombe FA. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2000 March; 9(2): 161-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983480&dopt=Abstract

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Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting. Author(s): Akehurst RL, Brazier JE, Mathers N, O'Keefe C, Kaltenthaler E, Morgan A, Platts M, Walters SJ. Source: Pharmacoeconomics. 2002; 20(7): 455-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093301&dopt=Abstract

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Health-related quality of life and health care costs in severe, refractory irritable bowel syndrome. Author(s): Creed F, Ratcliffe J, Fernandez L, Tomenson B, Palmer S, Rigby C, Guthrie E, Read N, Thompson D. Source: Annals of Internal Medicine. 2001 May 1; 134(9 Pt 2): 860-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11346322&dopt=Abstract

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Health-related quality of life associated with irritable bowel syndrome: comparison with other chronic diseases. Author(s): Frank L, Kleinman L, Rentz A, Ciesla G, Kim JJ, Zacker C. Source: Clinical Therapeutics. 2002 April; 24(4): 675-89; Discussion 674. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017411&dopt=Abstract

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High prevalence of irritable bowel syndrome in patients attending urological outpatient departments. Author(s): Francis CY, Duffy JN, Whorwell PJ, Morris J. Source: Digestive Diseases and Sciences. 1997 February; 42(2): 404-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9052526&dopt=Abstract

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High-fiber diet supplementation in patients with irritable bowel syndrome (IBS): a multicenter, randomized, open trial comparison between wheat bran diet and partially hydrolyzed guar gum (PHGG). Author(s): Parisi GC, Zilli M, Miani MP, Carrara M, Bottona E, Verdianelli G, Battaglia G, Desideri S, Faedo A, Marzolino C, Tonon A, Ermani M, Leandro G. Source: Digestive Diseases and Sciences. 2002 August; 47(8): 1697-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184518&dopt=Abstract

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How bad are the symptoms and bowel dysfunction of patients with the irritable bowel syndrome? A prospective, controlled study with emphasis on stool form. Author(s): Heaton KW, Ghosh S, Braddon FE. Source: Gut. 1991 January; 32(1): 73-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1991641&dopt=Abstract

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How effective are antidepressant medications in the treatment of irritable bowel syndrome and nonulcer dyspepsia? Author(s): Pearson RL. Source: The Journal of Family Practice. 2000 May; 49(5): 396. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10836766&dopt=Abstract

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Hydrogen breath test quantification and clinical correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis. Author(s): Sciarretta G, Giacobazzi G, Verri A, Zanirato P, Garuti G, Malaguti P. Source: Digestive Diseases and Sciences. 1984 December; 29(12): 1098-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6548690&dopt=Abstract

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Hypersensitivity and hyperreactivity in the irritable bowel syndrome: An opportunity for drug discovery. Author(s): Sanger GJ. Source: Digestive Diseases (Basel, Switzerland). 1999; 17(2): 90-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10545714&dopt=Abstract

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Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Author(s): Verne GN, Robinson ME, Price DD. Source: Pain. 2001 July; 93(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406333&dopt=Abstract

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Hypnosis treatment for severe irritable bowel syndrome: investigation of mechanism and effects on symptoms. Author(s): Palsson OS, Turner MJ, Johnson DA, Burnelt CK, Whitehead WE. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2605-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452403&dopt=Abstract

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Hypnotherapy and refractory irritable bowel syndrome: a single case study. Author(s): Galovski TE, Blanchard EB. Source: Am J Clin Hypn. 2002 July; 45(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116613&dopt=Abstract

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Hypnotherapy and therapeutic audiotape: effective in previously unsuccessfully treated irritable bowel syndrome? Author(s): Forbes A, MacAuley S, Chiotakakou-Faliakou E. Source: International Journal of Colorectal Disease. 2000 November; 15(5-6): 328-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151439&dopt=Abstract

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Hypnotherapy in irritable bowel syndrome: a large-scale audit of a clinical service with examination of factors influencing responsiveness. Author(s): Gonsalkorale WM, Houghton LA, Whorwell PJ. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 954-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003432&dopt=Abstract

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Hypothalamic digoxin and irritable bowel syndrome. Author(s): Kumar AR, Kurup PA. Source: Indian J Gastroenterol. 2001 September-October; 20(5): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11676326&dopt=Abstract

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Impact of irritable bowel syndrome: prevalence and effect on health-related quality of life. Author(s): El-Serag HB. Source: Reviews in Gastroenterological Disorders. 2003; 3 Suppl 2: S3-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775997&dopt=Abstract

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Impact of sex and gender on irritable bowel syndrome. Author(s): Heitkemper M, Jarrett M, Bond EF, Chang L. Source: Biological Research for Nursing. 2003 July; 5(1): 56-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886671&dopt=Abstract

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Infection as a cause of irritable bowel syndrome. Author(s): Spiller RC. Source: Hosp Med. 2003 May; 64(5): 270-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789735&dopt=Abstract

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Intestinal reactivity to words with emotional content and brain information processing in irritable bowel syndrome. Author(s): Blomhoff S, Spetalen S, Jacobsen MB, Vatn M, Malt UF. Source: Digestive Diseases and Sciences. 2000 June; 45(6): 1160-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877232&dopt=Abstract

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Irritable bowel syndrome and health-related quality of life: a population-based study in Calgary, Alberta. Author(s): Li FX, Patten SB, Hilsden RJ, Sutherland LR. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 April; 17(4): 259-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704470&dopt=Abstract

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Irritable bowel syndrome and mirtazapine. Author(s): Thomas SG. Source: The American Journal of Psychiatry. 2000 August; 157(8): 1341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910804&dopt=Abstract

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Irritable bowel syndrome in a psychiatric patient population. Author(s): North CS, Alpers DH. Source: Comprehensive Psychiatry. 2000 March-April; 41(2): 116-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741890&dopt=Abstract

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Irritable bowel syndrome in primary care: the patients' and doctors' views on symptoms, etiology and management. Author(s): Bijkerk CJ, de Wit NJ, Stalman WA, Knottnerus JA, Hoes AW, Muris JW. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 June; 17(6): 363-8; Quiz 405-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813601&dopt=Abstract

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Irritable bowel syndrome patients show altered sensitivity to exogenous opioids. Author(s): Lembo T, Naliboff BD, Matin K, Munakata J, Parker RA, Gracely RH, Mayer EA. Source: Pain. 2000 August; 87(2): 137-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924807&dopt=Abstract

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Irritable bowel syndrome. Author(s): Zaman A. Source: Clinical Cornerstone. 2002; 4(4): 22-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739324&dopt=Abstract

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Irritable bowel syndrome: a management strategy. Author(s): Thompson WG. Source: Bailliere's Best Practice & Research. Clinical Gastroenterology. 1999 October; 13(3): 453-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580921&dopt=Abstract

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Irritable bowel syndrome: an overview of diagnosis and pharmacologic treatment. Author(s): Olden KW. Source: Cleve Clin J Med. 2003 June; 70 Suppl 2: S3-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825862&dopt=Abstract

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Irritable bowel syndrome: are incentives useful for improving survey response rates? Author(s): Patten SB, Li FX, Cook T, Hilsden RJ, Sutherland LR. Source: Journal of Clinical Epidemiology. 2003 March; 56(3): 256-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725880&dopt=Abstract

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Irritable bowel syndrome: definition, diagnosis and epidemiology. Author(s): Talley NJ. Source: Bailliere's Best Practice & Research. Clinical Gastroenterology. 1999 October; 13(3): 371-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580915&dopt=Abstract

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Irritable bowel syndrome: epidemiology and diagnosis. Author(s): Ron Y. Source: Isr Med Assoc J. 2003 March; 5(3): 201-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725144&dopt=Abstract

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Irritable bowel syndrome: evaluation and treatment. Author(s): Somers SC, Lembo A. Source: Gastroenterology Clinics of North America. 2003 June; 32(2): 507-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858604&dopt=Abstract

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Irritable bowel syndrome: new pharmaceutical approaches to treatment. Author(s): Farthing MJ. Source: Bailliere's Best Practice & Research. Clinical Gastroenterology. 1999 October; 13(3): 461-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580922&dopt=Abstract

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Irritable bowel syndrome: new recommendations for diagnosis and treatment. Author(s): Lacy BE. Source: Archives of Internal Medicine. 2003 June 9; 163(11): 1374-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796080&dopt=Abstract

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Irritable bowel syndrome: unravelling the mysteries. Author(s): Hunter JO. Source: Hosp Med. 2003 May; 64(5): 262-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789733&dopt=Abstract

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Is irritable bowel syndrome more likely to be persistent in those with relatives who suffer from gastrointestinal symptoms? A population-based study at three time points. Author(s): Kalantar JS, Locke GR 3rd, Talley NJ, Zinsmeister AR, Fett SL, Melton LJ 3rd. Source: Alimentary Pharmacology & Therapeutics. 2003 June 1; 17(11): 1389-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786633&dopt=Abstract

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Jejunal sensorimotor dysfunction in irritable bowel syndrome: clinical and psychosocial features. Author(s): Evans PR, Bennett EJ, Bak YT, Tennant CC, Kellow JE. Source: Gastroenterology. 1996 February; 110(2): 393-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8566585&dopt=Abstract

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Kruis scoring system and Manning's criteria in diagnosis of irritable bowel syndrome: is it better to use combined? Author(s): Dogan UB, Unal S. Source: Acta Gastroenterol Belg. 1996 October-December; 59(4): 225-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085621&dopt=Abstract

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Lactose intolerance and irritable bowel syndrome. Author(s): Mascolo R, Saltzman JR. Source: Nutrition Reviews. 1998 October; 56(10): 306-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9810810&dopt=Abstract

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Lactose intolerance and irritable bowel syndrome. Author(s): Turnbull GK. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 July-August; 16(7-8): 6656. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10906590&dopt=Abstract

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Lactose intolerance in different types of irritable bowel syndrome in north Indians. Author(s): Rana SV, Mandal AK, Kochhar R, Katyal R, Singh K. Source: Trop Gastroenterol. 2001 October-December; 22(4): 202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11963325&dopt=Abstract

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Lactose malabsorption and irritable bowel syndrome. Effect of a long-term lactosefree diet. Author(s): Vernia P, Ricciardi MR, Frandina C, Bilotta T, Frieri G. Source: Ital J Gastroenterol. 1995 April; 27(3): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7548919&dopt=Abstract

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Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance. Author(s): Vernia P, Di Camillo M, Marinaro V. Source: Dig Liver Dis. 2001 April; 33(3): 234-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407668&dopt=Abstract

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Large-scale ambulatory study of postprandial jejunal motility in irritable bowel syndrome. Author(s): Small PK, Loudon MA, Hau CM, Noor N, Campbell FC. Source: Scandinavian Journal of Gastroenterology. 1997 January; 32(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9018765&dopt=Abstract

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Learning needs of Taiwanese nurses caring for patients with irritable bowel syndrome. Author(s): Chen H, McCutcheon H. Source: Nursing & Health Sciences. 2001 December; 3(4): 173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906625&dopt=Abstract

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Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Author(s): Bennett EJ, Tennant CC, Piesse C, Badcock CA, Kellow JE. Source: Gut. 1998 August; 43(2): 256-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10189854&dopt=Abstract

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Likely impacts of recruitment site and methodology on characteristics of enrolled patient population: irritable bowel syndrome clinical trial design. Author(s): Jones R. Source: The American Journal of Medicine. 1999 November 8; 107(5A): 85S-90S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10588178&dopt=Abstract

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Lines written on reading another review article about the irritable bowel syndrome. Author(s): Valori R. Source: Lancet. 1993 January 2; 341(8836): 36-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8093280&dopt=Abstract

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Lipid-induced colonic hypersensitivity in irritable bowel syndrome: the role of 5-HT3 receptors. Author(s): Simren M, Simms L, D'Souza D, Abrahamsson H, Bjornsson ES. Source: Alimentary Pharmacology & Therapeutics. 2003 January; 17(2): 279-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534414&dopt=Abstract

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Lipid-induced intestinal gas retention in irritable bowel syndrome. Author(s): Serra J, Salvioli B, Azpiroz F, Malagelada JR. Source: Gastroenterology. 2002 September; 123(3): 700-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198695&dopt=Abstract

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Long-term safety of tegaserod in patients with constipation-predominant irritable bowel syndrome. Author(s): Tougas G, Snape WJ Jr, Otten MH, Earnest DL, Langaker KE, Pruitt RE, Pecher E, Nault B, Rojavin MA. Source: Alimentary Pharmacology & Therapeutics. 2002 October; 16(10): 1701-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269961&dopt=Abstract

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Longterm treatment of irritable bowel syndrome with cimetropium bromide: a double blind placebo controlled clinical trial. Author(s): Dobrilla G, Imbimbo BP, Piazzi L, Bensi G. Source: Gut. 1990 March; 31(3): 355-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2182401&dopt=Abstract

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Lotronex(tm): therapy for diarrhea predominant irritable bowel syndrome. Author(s): McGahan L. Source: Issues Emerg Health Technol. 2000 October; (11): 1-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902219&dopt=Abstract

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Low dominance and high intropunitiveness in ulcerative colitis and irritable bowel syndrome. Author(s): Arapakis G, Lyketsos CG, Gerolymatos K, Richardson SC, Lyketsos GC. Source: Psychotherapy and Psychosomatics. 1986; 46(4): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3628684&dopt=Abstract

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Management of irritable bowel syndrome. Author(s): Gunn MC, Cavin AA, Mansfield JC. Source: Postgraduate Medical Journal. 2003 March; 79(929): 154-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697915&dopt=Abstract

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Management of irritable bowel syndrome. Author(s): Viera AJ, Hoag S, Shaughnessy J. Source: American Family Physician. 2002 November 15; 66(10): 1867-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469960&dopt=Abstract

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Management of irritable bowel syndrome. Author(s): De Giacomo C. Source: Gastroenterology. 2001 December; 121(6): 1527-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758547&dopt=Abstract

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Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. Author(s): Scarpignato C, Pelosini I. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 1999 March; 13 Suppl A: 50A-65A. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10202210&dopt=Abstract

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Management of irritable bowel syndrome: start of a new era? Author(s): Silk DB. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 679-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840681&dopt=Abstract

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Management of the irritable bowel syndrome. Author(s): Camilleri M. Source: Gastroenterology. 2001 February; 120(3): 652-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179242&dopt=Abstract

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Medical and lay views of irritable bowel syndrome. Author(s): Dixon-Woods M, Critchley S. Source: Family Practice. 2000 April; 17(2): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10758070&dopt=Abstract

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Medical literature implies continuous positive airway pressure might be appropriate treatment for irritable bowel syndrome. Author(s): Herr JR. Source: Chest. 2002 September; 122(3): 1107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226070&dopt=Abstract

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Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Author(s): Poynard T, Regimbeau C, Benhamou Y. Source: Alimentary Pharmacology & Therapeutics. 2001 March; 15(3): 355-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207510&dopt=Abstract

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Multicenter phase III clinical trial of otilonium bromide in irritable bowel syndrome. Author(s): Kaushik A, Pursnani ML, Kar P. Source: Indian J Gastroenterol. 2002 March-April; 21(2): 85-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990341&dopt=Abstract

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Naloxone treatment for irritable bowel syndrome--a randomized controlled trial with an oral formulation. Author(s): Hawkes ND, Rhodes J, Evans BK, Rhodes P, Hawthorne AB, Thomas GA. Source: Alimentary Pharmacology & Therapeutics. 2002 September; 16(9): 1649-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197844&dopt=Abstract

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Natural killer cell function and psychological distress in women with and without irritable bowel syndrome. Author(s): Motzer SA, Jarrett M, Heitkemper MM, Tsuji J. Source: Biological Research for Nursing. 2002 July; 4(1): 31-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363280&dopt=Abstract

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Neuropathophysiology of irritable bowel syndrome. Author(s): Wood JD. Source: Journal of Clinical Gastroenterology. 2002 July; 35(1 Suppl): S11-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184133&dopt=Abstract

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Neurotransmitter antagonism in management of irritable bowel syndrome. Author(s): Lembo T. Source: Lancet. 2000 March 25; 355(9209): 1030-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10744083&dopt=Abstract

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New approaches to the medical treatment of irritable bowel syndrome. Author(s): Berrada D, Canenguez K, Lembo T. Source: Current Gastroenterology Reports. 2003 August; 5(4): 337-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864965&dopt=Abstract

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New developments in the diagnosis and treatment of irritable bowel syndrome. Author(s): Longstreth GF, Drossman DA. Source: Current Gastroenterology Reports. 2002 October; 4(5): 427-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228046&dopt=Abstract

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New insights into the psychosocial aspects of irritable bowel syndrome. Author(s): Lea R, Whorwell PJ. Source: Current Gastroenterology Reports. 2003 August; 5(4): 343-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864966&dopt=Abstract

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Nongastrointestinal disorders in the irritable bowel syndrome. Author(s): Azpiroz F, Dapoigny M, Pace F, Muller-Lissner S, Coremans G, Whorwell P, Stockbrugger RW, Smout A. Source: Digestion. 2000; 62(1): 66-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899728&dopt=Abstract

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Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Author(s): Pimentel M, Chow EJ, Lin HC. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 412-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591062&dopt=Abstract

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Novel therapies in the treatment of irritable bowel syndrome. Author(s): Berrada D, Lembo T. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 635-45. Review. Erratum In: Expert Opin Investig Drugs. 2003 May; 12(5): 907. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665418&dopt=Abstract

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Objective evaluation of psychological abnormality in irritable bowel syndrome. Author(s): Chakraborti SK, Dey BK, Ghosh N, Chaudhury AN, Guha Mazumder DN. Source: Indian J Gastroenterol. 1996 April; 15(2): 43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8935932&dopt=Abstract

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Octylonium bromide in the treatment of the irritable bowel syndrome: a clinicalfunctional study. Author(s): Baldi F, Longanesi A, Blasi A, Monello S, Cestari R, Missale G, Corazziari E, Badiali G, Marzio L, Di Felice F, et al. Source: Hepatogastroenterology. 1992 October; 39(5): 392-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1459516&dopt=Abstract

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One-year follow-up of newly diagnosed irritable bowel syndrome patients. Author(s): Ruigomez A, Wallander MA, Johansson S, Garcia Rodriguez LA. Source: Alimentary Pharmacology & Therapeutics. 1999 August; 13(8): 1097-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468687&dopt=Abstract

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Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients. Author(s): Stefanini GF, Saggioro A, Alvisi V, Angelini G, Capurso L, di Lorenzo G, Dobrilla G, Dodero M, Galimberti M, Gasbarrini G, et al. Source: Scandinavian Journal of Gastroenterology. 1995 June; 30(6): 535-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7569760&dopt=Abstract

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Oral disodium cromoglycate treatment on irritable bowel syndrome: an open study on 101 subjects with diarrheic type. Author(s): Stefanini GF, Prati E, Albini MC, Piccinini G, Capelli S, Castelli E, Mazzetti M, Gasbarrini G. Source: The American Journal of Gastroenterology. 1992 January; 87(1): 55-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1728124&dopt=Abstract

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Otilonium bromide enhances sensory thresholds of volume and pressure in patients with irritable bowel syndrome. Author(s): Czimmer J, Suto G, Kiraly A, Mozsik G. Source: Journal of Physiology, Paris. 2001 January-December; 95(1-6): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595430&dopt=Abstract

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Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study. Author(s): Battaglia G, Morselli-Labate AM, Camarri E, Francavilla A, De Marco F, Mastropaolo G, Naccarato R. Source: Alimentary Pharmacology & Therapeutics. 1998 October; 12(10): 1003-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9798806&dopt=Abstract

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Outcome measures in irritable bowel syndrome: comparison of psychometric and methodological characteristics. Author(s): Bijkerk CJ, de Wit NJ, Muris JW, Jones RH, Knottnerus JA, Hoes AW. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526947&dopt=Abstract

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Outpatients with irritable bowel syndrome: a comparison of first time and chronic attenders. Author(s): Guthrie EA, Creed FH, Whorwell PJ, Tomenson B. Source: Gut. 1992 March; 33(3): 361-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1568655&dopt=Abstract

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Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome. Author(s): Louvel D, Delvaux M, Felez A, Fioramonti J, Bueno L, Lazorthes Y, Frexinos J. Source: Gut. 1996 November; 39(5): 741-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014776&dopt=Abstract

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Pain produced by electric stimulation of the rectum in patients with irritable bowel syndrome: further evidence of visceral hyperalgesia. Author(s): Rossel P, Drewes AM, Petersen P, Nielsen J, Arendt-Nielsen L. Source: Scandinavian Journal of Gastroenterology. 1999 October; 34(10): 1001-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563670&dopt=Abstract

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Patients with irritable bowel syndrome: health status and use of health care services. Author(s): Donker GA, Foets M, Spreeuwenberg P. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1999 October; 49(447): 787-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885081&dopt=Abstract

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Perceptual hyperreactivity to auditory stimuli in patients with irritable bowel syndrome. Author(s): Blomhoff S, Jacobsen MB, Spetalen S, Dahm A, Malt UF. Source: Scandinavian Journal of Gastroenterology. 2000 June; 35(6): 583-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912657&dopt=Abstract

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Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Author(s): Jailwala J, Imperiale TF, Kroenke K. Source: Annals of Internal Medicine. 2000 July 18; 133(2): 136-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896640&dopt=Abstract

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Physiological correlates of childhood abuse: chronic hyperarousal in PTSD, depression, and irritable bowel syndrome. Author(s): Kendall-Tackett KA. Source: Child Abuse & Neglect. 2000 June; 24(6): 799-810. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10888019&dopt=Abstract

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Potential pitfalls in the differential diagnosis of irritable bowel syndrome. Author(s): Smout A, Azpiroz F, Coremans G, Dapoigny M, Collins S, Muller-Lissner S, Pace F, Stockbrugger R, Vatn M, Whorwell P. Source: Digestion. 2000; 61(4): 247-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10878451&dopt=Abstract

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Predictive value of the Rome criteria for diagnosing the irritable bowel syndrome. Author(s): Vanner SJ, Depew WT, Paterson WG, DaCosta LR, Groll AG, Simon JB, Djurfeldt M. Source: The American Journal of Gastroenterology. 1999 October; 94(10): 2912-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10520844&dopt=Abstract

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Prevalence of microscopic colitis in patients with symptoms suggesting irritable bowel syndrome. Author(s): Tuncer C, Cindoruk M, Dursun A, Karakan T. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891921&dopt=Abstract

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Productivity loss due to irritable bowel syndrome. Author(s): Gandjour A. Source: Archives of Internal Medicine. 2003 October 13; 163(18): 2249; Author Reply 2249-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557225&dopt=Abstract

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Psychopathology in irritable bowel syndrome: support for a psychophysiological model. Author(s): Sykes MA, Blanchard EB, Lackner J, Keefer L, Krasner S. Source: Journal of Behavioral Medicine. 2003 August; 26(4): 361-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921009&dopt=Abstract

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Quality of life in irritable bowel syndrome, effect of therapy. Author(s): Chassany O, Bergmann JF. Source: Eur J Surg Suppl. 1998; (583): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10027679&dopt=Abstract

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Quality of life in irritable bowel syndrome. Author(s): Lea R, Whorwell PJ. Source: Pharmacoeconomics. 2001; 19(6): 643-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456212&dopt=Abstract

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Quality of life in patients with irritable bowel syndrome seen in referral centers versus primary care: the impact of gender and predominant bowel pattern. Author(s): Simren M, Abrahamsson H, Svedlund J, Bjornsson ES. Source: Scandinavian Journal of Gastroenterology. 2001 May; 36(5): 545-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11346211&dopt=Abstract

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Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Author(s): Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Source: Digestive Diseases and Sciences. 1998 February; 43(2): 400-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9512138&dopt=Abstract

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Quantitative analysis of bowel gas using plain abdominal radiograph in patients with irritable bowel syndrome. Author(s): Koide A, Yamaguchi T, Odaka T, Koyama H, Tsuyuguchi T, Kitahara H, Ohto M, Saisho H. Source: The American Journal of Gastroenterology. 2000 July; 95(7): 1735-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10925977&dopt=Abstract

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Randomized, double-blind, placebo-controlled trial of prednisolone in postinfectious irritable bowel syndrome. Author(s): Dunlop SP, Jenkins D, Neal KR, Naesdal J, Borgaonker M, Collins SM, Spiller RC. Source: Alimentary Pharmacology & Therapeutics. 2003 July 1; 18(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848628&dopt=Abstract

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Re: Brandt et al.--An evidence-based approach to the management of irritable bowel syndrome in North America. Author(s): Avigan M, Justice R, Mackey AC, Nair N. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2105-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499800&dopt=Abstract

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Rectal tone and brain information processing in irritable bowel syndrome. Author(s): Blomhoff S, Spetalen S, Jacobsen MB, Vatn M, Malt UF. Source: Digestive Diseases and Sciences. 2000 June; 45(6): 1153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877231&dopt=Abstract

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Recurrent abdominal pain in children: forerunner to adult irritable bowel syndrome? Author(s): Jarrett M, Heitkemper M, Czyzewski DI, Shulman R. Source: Journal for Specialists in Pediatric Nursing : Jspn. 2003 July-September; 8(3): 819. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942886&dopt=Abstract

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Regional brain activation in response to rectal distension in patients with irritable bowel syndrome and the effect of a history of abuse. Author(s): Ringel Y, Drossman DA, Turkington TG, Bradshaw B, Hawk TC, Bangdiwala S, Coleman RE, Whitehead WE. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1774-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561000&dopt=Abstract

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Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Author(s): Mertz H, Morgan V, Tanner G, Pickens D, Price R, Shyr Y, Kessler R. Source: Gastroenterology. 2000 May; 118(5): 842-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784583&dopt=Abstract

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Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients. Author(s): Verne GN, Robinson ME, Vase L, Price DD. Source: Pain. 2003 September; 105(1-2): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499439&dopt=Abstract

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Risk factor for irritable bowel syndrome: role of food allergies. Author(s): Addolorato G, Capristo E, Ghittoni G, Ancona C, Gasbarrini G. Source: The American Journal of Gastroenterology. 2000 August; 95(8): 2130-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950079&dopt=Abstract

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Risk factors in irritable bowel syndrome. Author(s): Hunt SC. Source: The American Journal of Gastroenterology. 2000 August; 95(8): 2129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950078&dopt=Abstract

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Role of food hypersensitivity in irritable bowel syndrome. Author(s): Zar S, Kumar D, Kumar D. Source: Minerva Med. 2002 October; 93(5): 403-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410172&dopt=Abstract

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Sense of coherence and quality of life in women with and without irritable bowel syndrome. Author(s): Motzer SA, Hertig V, Jarrett M, Heitkemper MM. Source: Nursing Research. 2003 September-October; 52(5): 329-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501547&dopt=Abstract

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Sensory dysfunction and the irritable bowel syndrome. Author(s): Houghton LA. Source: Bailliere's Best Practice & Research. Clinical Gastroenterology. 1999 October; 13(3): 415-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580918&dopt=Abstract

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Serotonergic modulators in the treatment of irritable bowel syndrome: influence on psychiatric and gastrointestinal symptoms. Author(s): Castle MZ, Silk DB, Libby GW. Source: Alimentary Pharmacology & Therapeutics. 2003 June 1; 17(11): 1425. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786637&dopt=Abstract

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Serotonin and its implication for the management of irritable bowel syndrome. Author(s): Gershon MD. Source: Reviews in Gastroenterological Disorders. 2003; 3 Suppl 2: S25-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776000&dopt=Abstract

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Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome. Author(s): Jarrett M, Heitkemper M, Cain KC, Burr RL, Hertig V. Source: Digestive Diseases and Sciences. 2000 May; 45(5): 952-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10795760&dopt=Abstract

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Stimulation of the nitric oxide-guanosine 3', 5'-cyclic monophosphate pathway by sildenafil: effect on rectal muscle tone, distensibility, and perception in health and in irritable bowel syndrome. Author(s): Fritz E, Hammer J, Schmidt B, Eherer AJ, Hammer HF. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2253-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14572576&dopt=Abstract

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Subject's Global Assessment of Relief: an appropriate method to assess the impact of treatment on irritable bowel syndrome-related symptoms in clinical trials. Author(s): Muller-Lissner S, Koch G, Talley NJ, Drossman D, Rueegg P, Dunger-Baldauf C, Lefkowitz M. Source: Journal of Clinical Epidemiology. 2003 April; 56(4): 310-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767407&dopt=Abstract

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Symptoms across the menstrual cycle in women with irritable bowel syndrome. Author(s): Heitkemper MM, Cain KC, Jarrett ME, Burr RL, Hertig V, Bond EF. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 420-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591063&dopt=Abstract

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Systematic review: Abdominal and pelvic surgery in patients with irritable bowel syndrome. Author(s): Hasler WL, Schoenfeld P. Source: Alimentary Pharmacology & Therapeutics. 2003 Apr15; 17(8): 997-1005. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694081&dopt=Abstract

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Systematic review: serotonergic modulators in the treatment of irritable bowel syndrome--influence on psychiatric and gastrointestinal symptoms. Author(s): Kilkens TO, Honig A, Rozendaal N, Van Nieuwenhoven MA, Brummer RJ. Source: Alimentary Pharmacology & Therapeutics. 2003 January; 17(1): 43-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492731&dopt=Abstract

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The association between Helicobacter pylori infection and functional dyspepsia in patients with irritable bowel syndrome. Author(s): Su YC, Wang WM, Wang SY, Lu SN, Chen LT, Wu DC, Chen CY, Jan CM, Horowitz M. Source: The American Journal of Gastroenterology. 2000 August; 95(8): 1900-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950033&dopt=Abstract

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The combination of medical treatment plus multicomponent behavioral therapy is superior to medical treatment alone in the therapy of irritable bowel syndrome. Author(s): Heymann-Monnikes I, Arnold R, Florin I, Herda C, Melfsen S, Monnikes H. Source: The American Journal of Gastroenterology. 2000 April; 95(4): 981-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763948&dopt=Abstract

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The many faces of irritable bowel syndrome. Author(s): Gwee KA. Source: Singapore Med J. 1999 July; 40(7): 441-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10560266&dopt=Abstract

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The measurement of irritable bowel syndrome (IBS)-related misconceptions in people with IBS. Author(s): Dancey CP, Fox R, Devins GM. Source: Journal of Psychosomatic Research. 1999 September; 47(3): 269-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10576475&dopt=Abstract

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The problem of gas in irritable bowel syndrome. Author(s): Whorwell PJ. Source: The American Journal of Gastroenterology. 2000 July; 95(7): 1618-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10925958&dopt=Abstract

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The role of psychosocial factors in irritable bowel syndrome. Author(s): Gaynes BN, Drossman DA. Source: Bailliere's Best Practice & Research. Clinical Gastroenterology. 1999 October; 13(3): 437-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580920&dopt=Abstract

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The understanding of their illness amongst people with irritable bowel syndrome: a Q methodological study. Author(s): Stenner PH, Dancey CP, Watts S. Source: Social Science & Medicine (1982). 2000 August; 51(3): 439-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10855930&dopt=Abstract

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Towards an integrative model of irritable bowel syndrome. Author(s): Naliboff BD, Chang L, Munakata J, Mayer EA. Source: Prog Brain Res. 2000; 122: 413-23. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737074&dopt=Abstract

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Treatment of irritable bowel syndrome with loperamide oxide. An open study to determine optimal dosage. Author(s): Ragnarsson G, Bodemar G. Source: Journal of Internal Medicine. 2000 August; 248(2): 165-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947896&dopt=Abstract

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Treatment of irritable bowel syndrome: new modalities for a new millennium. Author(s): Olden KW. Source: The American Journal of Gastroenterology. 2000 April; 95(4): 863-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763925&dopt=Abstract

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Understanding irritable bowel syndrome and gastrointestinal motility. Author(s): Lind CD. Source: Mayo Clinic Proceedings. 1992 August; 67(8): 804-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1434922&dopt=Abstract

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Understanding the irritable bowel syndrome. Author(s): Young GP. Source: Aust Fam Physician. 1987 April; 16(4): 392-6, 399, 404. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3593106&dopt=Abstract

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University of Miami Division of Clinical Pharmacology therapeutic rounds: irritable bowel syndrome-pathophysiology, diagnosis, and treatment. Author(s): Schwartz D, Stollman N. Source: American Journal of Therapeutics. 2000 August; 7(4): 265-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486161&dopt=Abstract

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Update in the therapeutic management of irritable bowel syndrome. Author(s): Villanueva A, Dominguez-Munoz JE, Mearin F. Source: Digestive Diseases (Basel, Switzerland). 2001; 19(3): 244-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752844&dopt=Abstract

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Update: irritable bowel syndrome. Author(s): Smith JN. Source: Mo Med. 1979 May; 76(5): 262-4, 269. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=440268&dopt=Abstract

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Upper gastrointestinal and mental symptoms in the irritable bowel syndrome. Author(s): Svedlund J, Sjodin I, Dotevall G, Gillberg R. Source: Scandinavian Journal of Gastroenterology. 1985 June; 20(5): 595-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4023624&dopt=Abstract

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Use of a novel electronic data collection system in multicenter studies of irritable bowel syndrome. Author(s): Harding JP, Hamm LR, Ehsanullah RS, Heath AT, Sorrells SC, Haw J, Dukes GE, Wolfe SG, Mangel AW, Northcutt AR. Source: Alimentary Pharmacology & Therapeutics. 1997 December; 11(6): 1073-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9663832&dopt=Abstract

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Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia. Author(s): Sperber AD, Carmel S, Atzmon Y, Weisberg I, Shalit Y, Neumann L, Fich A, Friger M, Buskila D. Source: The American Journal of Gastroenterology. 2000 April; 95(4): 995-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763949&dopt=Abstract

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Use of the peripheral dopamine antagonist, domperidone, in the management of gastro-intestinal symptoms in patients with irritable bowel syndrome. Author(s): Milo R. Source: Current Medical Research and Opinion. 1980; 6(9): 577-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6996928&dopt=Abstract

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Utility of the Rome I and Rome II criteria for irritable bowel syndrome in U.S. women. Author(s): Chey WD, Olden K, Carter E, Boyle J, Drossman D, Chang L. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2803-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425552&dopt=Abstract

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V. Stress and irritable bowel syndrome. Author(s): Mayer EA, Naliboff BD, Chang L, Coutinho SV. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2001 April; 280(4): G519-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254476&dopt=Abstract

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Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Author(s): Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Source: Digestive Diseases and Sciences. 2003 July; 48(7): 1317-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870789&dopt=Abstract

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Validity of the Family APGAR in patients with irritable bowel syndrome. Author(s): Gwyther RE, Bentz EJ, Drossman DA, Berolzheimer N. Source: Family Medicine. 1993 January; 25(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8454119&dopt=Abstract

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Verapamil effective in irritable bowel syndrome? Author(s): McLeod J. Source: The Medical Journal of Australia. 1983 August 6; 2(3): 119. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6877141&dopt=Abstract

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Verapamil in the treatment of irritable bowel syndrome. Author(s): Byrne S. Source: The Journal of Clinical Psychiatry. 1987 September; 48(9): 388. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3624216&dopt=Abstract

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Visceral afferent hypersensitivity in irritable bowel syndrome--evaluation by cerebral evoked potential after rectal stimulation. Author(s): Sinhamahapatra P, Saha SP, Chowdhury A, Chakrabarti SK, Ghosh A, Maiti B. Source: The American Journal of Gastroenterology. 2001 July; 96(7): 2150-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11467647&dopt=Abstract

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Visceral algesia in irritable bowel syndrome, fibromyalgia, and sphincter of oddi dysfunction, type III. Author(s): Chun A, Desautels S, Slivka A, Mitrani C, Starz T, DiLorenzo C, Wald A. Source: Digestive Diseases and Sciences. 1999 March; 44(3): 631-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080161&dopt=Abstract

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Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distension and serotonin type 3 antagonism. Author(s): Zighelboim J, Talley NJ, Phillips SF, Harmsen WS, Zinsmeister AR. Source: Digestive Diseases and Sciences. 1995 April; 40(4): 819-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7720476&dopt=Abstract

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What can be done to control incontinence associated with the irritable bowel syndrome? Author(s): Drossman DA. Source: The American Journal of Gastroenterology. 1989 April; 84(4): 355-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2929552&dopt=Abstract

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What do patients with irritable bowel syndrome dream about? A comparison with inflammatory bowel disease. Author(s): Lal S, Whorwell PJ. Source: Dig Liver Dis. 2002 July; 34(7): 506-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236484&dopt=Abstract

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What is the benefit of coarse wheat bran in patients with irritable bowel syndrome? Author(s): Cann PA, Read NW, Holdsworth CD. Source: Gut. 1984 February; 25(2): 168-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6319244&dopt=Abstract

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What is the relevance of a systematic review of pharmacological management in irritable bowel syndrome to older people? Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Author(s): Camilleri M, Kim DY. Source: Journal of the American Geriatrics Society. 2001 September; 49(9): 1249-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559387&dopt=Abstract

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Wheat fibre and irritable bowel syndrome. A controlled trial. Author(s): Manning AP, Heaton KW, Harvey RF. Source: Lancet. 1977 August 27; 2(8035): 417-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=70639&dopt=Abstract

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Which is the best distension protocol to study rectal sensitivity in the irritable bowel syndrome? Author(s): Rey E, Alvarez Sanchez A, Diaz-Rubio M. Source: Rev Esp Enferm Dig. 2002 April; 94(4): 211-20. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185932&dopt=Abstract

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Who gets irritable bowel syndrome and does seeing a gastroenterologist affect its course? Author(s): Bernstein CN. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 October; 15 Suppl B: 5B-7B. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694907&dopt=Abstract

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Whole-bowel transit in patients with the irritable bowel syndrome. Author(s): Hardy JG, Wood E, Clark AG, Reynolds JR. Source: European Journal of Nuclear Medicine. 1986; 11(10): 393-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3699063&dopt=Abstract

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Women with irritable bowel syndrome: differences in patients' and physicians' perceptions. Author(s): Heitkemper M, Carter E, Ameen V, Olden K, Cheng L. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2002 September-October; 25(5): 192-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394395&dopt=Abstract

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CHAPTER 2. SYNDROME

NUTRITION

AND

IRRITABLE

BOWEL

Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and irritable bowel syndrome.

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

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

110 Irritable Bowel Syndrome

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

A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Author(s): Department of Gastroenterology, M. Curie Regional Hospital, Szczecin, Poland. [email protected] Source: Niedzielin, K Kordecki, H Birkenfeld, B Eur-J-Gastroenterol-Hepatol. 2001 October; 13(10): 1143-7 0954-691X

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A dietary remedy for irritable bowel syndrome. Source: Cerrato, P L RN. 1987 July; 50(7): 65-6 0033-7021

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A new look at irritable bowel syndrome [IBS]: a neuroenteric disorder. Author(s): Weill Medical College of Cornell University, New York, NY, USA. Source: Frissora, C L Compr-Ther. 2002 Fall; 28(3): 222-31 0098-8243

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A novel treatment for constipation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula. Author(s): The Natural Medicine Research Unit, Hadassah University Hospital, Jerusalem, Israel. [email protected] Source: Sallon, S Ben Arye, E Davidson, R Shapiro, H Ginsberg, G Ligumsky, M Digestion. 2002; 65(3): 161-71 0012-2823

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A review of the role of the gut microflora in irritable bowel syndrome and the effects of probiotics. Author(s): Gastroenterology Research Unit, Unit E7, Box 201 A, Addenbrookes NHS Trust, Hill's Road, CB2 2QQ, Cambridge, UK. Source: Madden, J A Hunter, J O Br-J-Nutr. 2002 September; 88 Suppl 1: S67-72 00071145

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A single-blind trial of reflexology for irritable bowel syndrome. Author(s): School of Healthcare Studies, University of Leeds. [email protected] Source: Tovey, Philip Br-J-Gen-Pract. 2002 January; 52(474): 19-23 0960-1643

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A systematic review of alternative therapies in the irritable bowel syndrome. Author(s): Department of Internal Medicine, Northwestern Memorial Hospital, 251 E Huron, Galter 4-104, Chicago, IL 60611, USA. Source: Spanier, J A Howden, C W Jones, M P Arch-Intern-Med. 2003 February 10; 163(3): 265-74 0003-9926

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Abnormalities of GI transit in bloated irritable bowel syndrome: effect of bran on transit and symptoms. Author(s): Department of Gastroenterology, University Hospital Nottingham, United Kingdom. Source: Hebden, J M Blackshaw, E D'Amato, M Perkins, A C Spiller, R C Am-JGastroenterol. 2002 September; 97(9): 2315-20 0002-9270

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Aleatory clinical study comparing otilonium bromide with a fiber-rich diet in the treatment of irritable bowel syndrome. Author(s): Gastroenterology Unit, Germans Trias i Pujol Hospital Badalona, Barcelona, Spain. Source: Villagrasa, M Boix, J Humbert, P Quer, J C Ital-J-Gastroenterol. 1991 November; 23(8 Suppl 1): 67-70 0392-0623

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Alosetron (Lotronex) is back: should I use it to treat my patients with irritable bowel syndrome? Author(s): Department of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, OH 44195, USA. Source: Shen, B Soffer, E E Cleve-Clin-J-Med. 2003 January; 70(1): 64-5 0891-1150

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Anisocoria associated with the medical treatment of irritable bowel syndrome. Author(s): Department of Ophthalmology, Ochsner Clinic, New Orleans, Louisiana 70121, USA. Source: Nussdorf, J D Berman, E L J-Neuroophthalmol. 2000 June; 20(2): 100-1 1070-8022

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Arrowroot as a treatment for diarrhoea in irritable bowel syndrome patients: a pilot study. Author(s): Department of Gastroenterologist, Leicester General Hospital, U.K. Source: Cooke, C Carr, I Abrams, K Mayberry, J Arq-Gastroenterol. 2000 Jan-March; 37(1): 20-4 0004-2803

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Bacterial supplementation in the irritable bowel syndrome. A randomised doubleblind placebo-controlled crossover study. Author(s): Department of Gastroenterology, Adelaide & Meath Hospital, Tallaght, Dublin, Ireland. Source: O'Sullivan, M A O'Morain, C A Dig-Liver-Dis. 2000 May; 32(4): 294-301

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Carbohydrate malabsorption and the effect of dietary restriction on symptoms of irritable bowel syndrome and functional bowel complaints. Author(s): Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel. Source: Goldstein, R Braverman, D Stankiewicz, H Isr-Med-Assoc-J. 2000 August; 2(8): 583-7 1565-1088

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Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome. Author(s): Department of Gastroenterology and Infectious Diseases, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, D-12200 Berlin, Germany. [email protected] Source: Wahnschaffe, U Ullrich, R Riecken, E O Schulzke, J D Gastroenterology. 2001 December; 121(6): 1329-38 0016-5085

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Charcoal tablets in the treatment of patients with irritable bowel syndrome. Author(s): Berolina Drug Development GmbH, Neuenhagen, Germany. Source: Hubner, W D Moser, E H Adv-Ther. 2002 Sep-October; 19(5): 245-52 0741-238X

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Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome. Author(s): Mayo Clinic, Rochesster, MN 55905, USA. [email protected] Source: Camilleri, M Heading, R C Thompson, W G Aliment-Pharmacol-Ther. 2002 August; 16(8): 1407-30 0269-2813

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Constipation, diarrhea, and irritable bowel syndrome. Author(s): Attending Colon and Rectal Surgeon, Department of Surgery, Wilford Hall Medical Center, San Antonio, Texas, USA. Source: Browning, S M Prim-Care. 1999 March; 26(1): 113-39 0095-4543

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Contemporary thoughts on the treatment of irritable bowel syndrome. Source: Giaquinta, D Manag-Care-Interface. 2002 August; 15(8): 19-20, 22

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Current concepts in the management of the irritable bowel syndrome. Author(s): Bowel Disease and Motility Center, Long Beach Memorial Medical Center, CA.

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Source: Snape, W J Rev-Gastroenterol-Mex. 1994 Apr-June; 59(2): 127-32 0375-0906 •

Dealing with irritable bowel syndrome. Author(s): Department of Medicine, Aga Khan University Hospital, Karachi. Source: Abbas, Z J-Pak-Med-Assoc. 1999 March; 49(3): 78-81 concl 0030-9982

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Diet in the irritable bowel syndrome. Author(s): Gastroenterology & Nutrition Section, Norwalk Hospital, Yale University School of Medicine, Norwalk, Connecticut, USA. [email protected] Source: Floch, M H Narayan, R J-Clin-Gastroenterol. 2002 July; 35(1 Suppl): S45-52 01920790

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Diet triggers symptoms in women with irritable bowel syndrome. The patient's perspective. Author(s): Department of Biobehavioral Nursing and Health Systems, University of Washington, Box 357266, Seattle, WA 98195-7266, USA. [email protected] Source: Jarrett, M Visser, R Heitkemper, M Gastroenterol-Nurs. 2001 Sep-October; 24(5): 246-52 1042-895X

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Dietary treatment of irritable bowel syndrome: current evidence and guidelines for future practice. Source: Burden, S. J-hum-nutr-diet. Oxford : Blackwell Science Ltd. June 2001. volume 14 (3) page 231-241. 0952-3871

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Drug therapy options for patients with irritable bowel syndrome. Source: Talley, N J Am-J-Manag-Care. 2001 July; 7(8 Suppl): S261-7 1096-1860

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Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers. Author(s): Gastrointestinal Research Unit, Departments of Gastroenterology and Surgery, University Medical Center Utrecht, The Netherlands. Source: Clemens, C H Samsom, M Van Berge Henegouwen, G P Fabri, M Smout, A J Aliment-Pharmacol-Ther. 2002 May; 16(5): 993-1002 0269-2813

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Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of irritable bowel syndrome. Author(s): Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK. Source: Sen, S Mullan, M M Parker, T J Woolner, J T Tarry, S A Hunter, J O Dig-Dis-Sci. 2002 November; 47(11): 2615-20 0163-2116

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Effect of red chillies on small bowel and colonic transit and rectal sensitivity in men with irritable bowel syndrome. Author(s): Department of Gastroenterology, B Y L Nair Hospital and T N Medical College, Mumbai. Source: Agarwal, M K Bhatia, S J Desai, S A Bhure, U Melgiri, S Indian-J-Gastroenterol. 2002 Sep-October; 21(5): 179-82 0254-8860

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Effects of probiotic administration upon the composition and enzymatic activity of human fecal microbiota in patients with irritable bowel syndrome or functional diarrhea. Author(s): Dipartimento di Scienze Farmaceutiche, Universita di Bologna, Italy. [email protected] Source: Brigidi, P Vitali, B Swennen, E Bazzocchi, G Matteuzzi, D Res-Microbiol. 2001 October; 152(8): 735-41 0923-2508

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Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. Author(s): Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan. Source: Liu, J H Chen, G H Yeh, H Z Huang, C K Poon, S K J-Gastroenterol. 1997 December; 32(6): 765-8 0944-1174

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Evaluation of hydrogen excretion after lactulose administration as a screening test for causes of irritable bowel syndrome. Author(s): Department of Gastroenterology, Addenbrooke's Hospital NHS Trust, Hills Road, Cambridge CB2 2QQ, UK. Source: Sen, S Dear, K L King, T S Elia, M Hunter, J O Eur-J-Gastroenterol-Hepatol. 2002 July; 14(7): 753-6 0954-691X

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Evidence-based position statement on the management of irritable bowel syndrome in North America. Source: Am-J-Gastroenterol. 2002 November; 97(11 Suppl): S1-5 0002-9270

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FDA OK's two drugs for irritable bowel syndrome. The arsenal of IBS drugs is growing, but diagnosis is tricky. Author(s): Section of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania, USA. Source: Horwitz, B J Health-News. 2002 October; 8(10): 1-2 1081-5880

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Functional diagnostic work-up in patients with irritable bowel syndrome. Author(s): Department of Gastroenterology, University of Munich, Germany. Source: Klauser, A G Voderholzer, W A Schindlbeck, N E Muller Lissner, S A ZGastroenterol. 1996 May; 34(5): 273-8 0044-2771

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Health-related quality of life and associated psychosocial factors in irritable bowel syndrome: a review. Author(s): [email protected] Source: Luscombe, F A Qual-Life-Res. 2000 March; 9(2): 161-76 0962-9343

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High-fiber diet supplementation in patients with irritable bowel syndrome (IBS): a multicenter, randomized, open trial comparison between wheat bran diet and partially hydrolyzed guar gum (PHGG). Author(s): Servizio di Gastroenterologia, Casa di Cura Abano Terme USL 16, Padova, Italy. Source: Parisi, G C Zilli, M Miani, M P Carrara, M Bottona, E Verdianelli, G Battaglia, G Desideri, S Faedo, A Marzolino, C Tonon, A Ermani, M Leandro, G Dig-Dis-Sci. 2002 August; 47(8): 1697-704 0163-2116

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Hypnotherapy and therapeutic audiotape: effective in previously unsuccessfully treated irritable bowel syndrome? Author(s): St Mark's Hospital, Watford Road, Harrow HA1 3UJ, UK. [email protected] Source: Forbes, A MacAuley, S Chiotakakou Faliakou, E Int-J-Colorectal-Dis. 2000 November; 15(5-6): 328-34 0179-1958

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I am 51 years old, perimenopausal, have irritable bowel syndrome and a family history of breast cancer, and am told my bones are thinning. These conditions would seem to rule out my use of estrogen or Fosamax. I weight train and take 1,500 mg of calcium a day to stave off osteoporosis. What's left? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 November; 6(3): 8 1070910X

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Impact of irritable bowel syndrome on personal relationships and working practices. Author(s): Department of Gastroenterology & Nutrition, Central Middlesex Hospital, The North West London Hospitals NHS Trust, London, UK. Source: Silk, D B Eur-J-Gastroenterol-Hepatol. 2001 November; 13(11): 1327-32 0954691X

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Inflammatory bowel disease and irritable bowel syndrome. Author(s): Johns Hopkins University School of Medicine, Baltimore, Maryland. Source: Bayless, T M Harris, M L Med-Clin-North-Am. 1990 January; 74(1): 21-8 00257125

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Interventions for irritable bowel syndrome: a nursing model. Source: Heitkemper, M Levy, R L Jarrett, M Bond, E F Gastroenterol-Nurs. 1995 NovDecember; 18(6): 224-30 1042-895X

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Intestinal microflora and oral bacteriotherapy in irritable bowel syndrome. Author(s): Dept. of Internal Medicine and Gastroenterology, Bellana Hospital, University of Bologna, Italy. [email protected] Source: Bazzocchi, G Gionchetti, P Almerigi, P F Amadini, C Campieri, M Dig-Liver-Dis. 2002 September; 34 Suppl 2: S48-53 1590-8658

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Irritable bowel syndrome and Crohn's disease. Source: Jones, VolumeA. Hunter, J.O. Food allergy and intolerance / [edited by] Jonathan Brostoff, Stephen J. Challacombe. London : Bailli'ere Tindall, 1987. page 555569. ISBN: 0702011568

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Lactose malabsorption and irritable bowel syndrome. Effect of a long-term lactosefree diet. Author(s): Cattedra di Gastroenterologia I, Universita La Sapienza, Roma, Italy. Source: Vernia, P Ricciardi, M R Frandina, C Bilotta, T Frieri, G Ital-J-Gastroenterol. 1995 April; 27(3): 117-21 0392-0623

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Lipid-induced intestinal gas retention in irritable bowel syndrome. Author(s): Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain. Source: Serra, J Salvioli, B Azpiroz, F Malagelada, J R Gastroenterology. 2002 September; 123(3): 700-6 0016-5085

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Living with irritable bowel syndrome. Source: Anonymous Nursing. 1999 September; 29(9): 20 0360-4039

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Long-term treatment of irritable bowel syndrome: results of a randomized controlled trial. Author(s): Department of Gastroenterology, G. B. Pant Hospital, New Delhi, India. Source: Misra, S P Thorat, V K Sachdev, G K Anand, B S Q-J-Med. 1989 October; 73(270): 931-9 0033-5622

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Management of irritable bowel syndrome. Author(s): Naval Hospital Jacksonville, Jacksonville, Florida, USA. [email protected] Source: Viera, A J Hoag, S Shaughnessy, J Am-Fam-Physician. 2002 November 15; 66(10): 1867-74 0002-838X

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Managing irritable bowel syndrome. Source: Alderman, J Adv-Nurse-Pract. 1999 January; 7(1): 40-1, 45-6, 78 1096-6293

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New developments in the diagnosis and treatment of irritable bowel syndrome. Author(s): Department of Gastroenterology, Kaiser Permanente Medical Care Program, 4647 Zion Avenue, San Diego, CA 92120, USA. [email protected] Source: Longstreth, G F Drossman, D A Curr-Gastroenterol-Repage 2002 October; 4(5): 427-34 1522-8037

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Nutritional issues in irritable bowel syndrome. Author(s): Division of Gastroenterology, University Hospital, Nottingham, UK. Source: Dunlop, S P Spiller, R C Curr-Opin-Clin-Nutr-Metab-Care. 2001 November; 4(6): 537-40 1363-1950

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Patient satisfaction with alosetron for the treatment of women with diarrheapredominant irritable bowel syndrome. Author(s): Mayo Clinic Scottsdale, Scottsdale, Arizona, USA. Source: Olden, K DeGarmo, R G Jhingran, P Bagby, B Decker, C Markowitz, M Carter, E Bobbitt, W Dahdul, A DeCastro, E Gringeri, L Johanson, J Levinson, L Mula, G Poleynard, G Stoltz, R R Truesdale, R Young, D Am-J-Gastroenterol. 2002 Dec; 97(12): 3139-46 0002-9270

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Quality of life in irritable bowel syndrome, effect of therapy. Author(s): Therapeutics Research Unit, Lariboisiere Hospital, Paris, France. Source: Chassany, O Bergmann, J F Eur-J-Surg-Suppl. 1998; (583): 81-6

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Reduction by cimetropium bromide of the colonic motor response to eating in patients with the irritable bowel syndrome. Author(s): Istituto di Clinica Medica e Gastroenterologia, Universita di Bologna, Italy. Source: Lanfranchi, G A Bazzocchi, G Campieri, M Brignola, C Fois, F Imbimbo, B P EurJ-Clin-Pharmacol. 1988; 33(6): 571-5 0031-6970

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Reduction of post-prandial motility by pinaverium bromide a calcium channel blocker acting selectively on the gastrointestinal tract in patients with irritable bowel syndrome. Author(s): Experimental Medicine and Motility Unit, Ministry of Health, Mexico City General Hospital; Mexico D.F. [email protected] Source: Awad, R A Cordova, V H Dibildox, M Santiago, R Camacho, S ActaGastroenterol-Latinoam. 1997; 27(4): 247-51 0300-9033

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Risk of irritable bowel syndrome among asthma patients. Author(s): Centro Espanol de Investigacion Farmacoepidemiologica (CEIFE), Madrid, Spain. [email protected] Source: Huerta, C Garcia Rodriguez, L A Wallander, M A Johansson, S Pharmacoepidemiol-Drug-Saf. 2002 Jan-February; 11(1): 31-5 1053-8569

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Role of dietary fibre in irritable bowel syndrome: a clinical study. Source: Sharma, S Saini, R K Goswami, S K Sharma, A Singh, S Indian-J-Med-Sci. 1987 February; 41(2): 29-33 0019-5359

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Role of food hypersensitivity in irritable bowel syndrome. Author(s): OGEM Department, St. Georges Hospital Medical School, London, UK. Source: Zar, S KuMarch, D Kumar, D Minerva-Med. 2002 October; 93(5): 403-12 00264806

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Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Author(s): Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Foundation, Rochester, Minnesota 55905, USA. [email protected]

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Source: Camilleri, Michael Atanasova, Elena Carlson, Paula J Ahmad, Umraan Kim, H Jae Viramontes, Blanca E McKinzie, Sanna Urrutia, Raul Gastroenterology. 2002 August; 123(2): 425-32 0016-5085 •

Systematic review on the management of irritable bowel syndrome in North America. Author(s): Albert Einstein College of Medicine, Bronx, NY, USA. Source: Brandt, L J Bjorkman, D Fennerty, M B Locke, G R Olden, K Peterson, W Quigley, E Schoenfeld, P Schuster, M Talley, N Am-J-Gastroenterol. 2002 November; 97(11 Suppl): S7-26 0002-9270

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Tegaserod for the treatment of constipation-predominant irritable bowel syndrome. Author(s): Drug Information Center, College of Pharmacy, Washington State University, Spokane, WA, USA. Source: Baker, D E Rev-Gastroenterol-Disord. 2001; 1(4): 187-98 1533-001X

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The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients. Author(s): CURE Digestive Diseases Research Center / Neuroenteric Disease Program, Department of Medicine, University of California School of Medicine, Los Angeles, CA 90073, USA. [email protected] Source: Mayer, E A Berman, S Derbyshire, S W Suyenobu, B Chang, L Fitzgerald, L Mandelkern, M Hamm, L Vogt, B Naliboff, B D Aliment-Pharmacol-Ther. 2002 July; 16(7): 1357-66 0269-2813

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The management of irritable bowel syndrome: a European, primary and secondary care collaboration. Author(s): University of Ottawa, Ontario, Canada. [email protected] Source: Thompson, W G Hungin, A P Neri, M Holtmann, G Sofos, S Delvaux, M Caballero Plasencia, A Eur-J-Gastroenterol-Hepatol. 2001 August; 13(8): 933-9 0954-691X

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The non-effect of pirenzepine in dietary resistant irritable bowel syndrome. Source: Gilvarry, J Kenny, A Fielding, J F Ir-J-Med-Sci. 1989 October; 158(10): 262 00211265

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The treatment of functional dyspepsia with red pepper. Author(s): Department of Internal Medicine, University of Bologna, Via Massarenti 48, 40138 Bologna, Italy. [email protected] Source: Bortolotti, M Coccia, G Grossi, G Miglioli, M Aliment-Pharmacol-Ther. 2002 June; 16(6): 1075-82 0269-2813

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The treatment of irritable bowel syndrome. Author(s): University of Ottawa, Ottawa, Ontario, Canada. [email protected] Source: Thompson, W G Aliment-Pharmacol-Ther. 2002 August; 16(8): 1395-406 02692813

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Therapeutic strategy for the irritable bowel syndrome. Author(s): Cattedra di Gastroenterologia, II Facolta, Universita di Napoli, Italy. Source: Castiglione, F Daniele, B Mazzacca, G Ital-J-Gastroenterol. 1991 November; 23(8 Suppl 1): 53-5 0392-0623

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Treating irritable bowel syndrome. Author(s): Digestion Health Center, University of Virginia Health Science Center, USA. Source: Bickston, S J Health-News. 1999 January 5; 5(1): 3 1081-5880

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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The following is a specific Web list relating to irritable bowel syndrome; 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: •

Food and Diet Barley Source: Healthnotes, Inc.; www.healthnotes.com Fructo-Oligosaccharides (FOS) and Other Oligosaccharides Source: Healthnotes, Inc.; www.healthnotes.com Juices Source: Healthnotes, Inc.; www.healthnotes.com Milk Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,95,00.html Natural Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Refined Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Rhubarb Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Rye Source: Healthnotes, Inc.; www.healthnotes.com Sugar Alcohols Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com Wheat Source: Healthnotes, Inc.; www.healthnotes.com

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

A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome. Author(s): Boyce PM, Talley NJ, Balaam B, Koloski NA, Truman G. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14572570&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to irritable bowel syndrome; 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 Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Constipation Source: Healthnotes, Inc.; www.healthnotes.com Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Irritable Bowel Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Irritable Bowel Syndrome Alternative names: Spastic Colon Source: Prima Communications, Inc.www.personalhealthzone.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com

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Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Spastic Colon Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc.; www.healthnotes.com •

Alternative Therapy Acupuncture Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,663,00.html Ayurveda Source: Integrative Medicine Communications; www.drkoop.com Ayurveda Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,672,00.html Biofeedback Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,675,00.html Hydrotherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,705,00.html Hypnotherapy Source: Healthnotes, Inc.; www.healthnotes.com Hypnotherapy Source: Integrative Medicine Communications; www.drkoop.com Hypnotherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,706,00.html Meditation Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html Reflexology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,730,00.html Traditional Chinese Medicine Source: Integrative Medicine Communications; www.drkoop.com Traditional Chinese Medicine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10085,00.html Yoga Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,746,00.html •

Chinese Medicine Guizhi Alternative names: Cassia Twig; Ramulus Cinnamomi Source: Chinese Materia Medica

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Homeopathy Argentum Nitricum Source: Healthnotes, Inc.; www.healthnotes.com Asafoetida Source: Healthnotes, Inc.; www.healthnotes.com Lilium Tigrinum Source: Healthnotes, Inc.; www.healthnotes.com Lycopodium Source: Healthnotes, Inc.; www.healthnotes.com Nux Vomica Source: Healthnotes, Inc.; www.healthnotes.com Podophyllum Source: Healthnotes, Inc.; www.healthnotes.com Sulphur Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Acidophilus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,748,00.html Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com Aloe Alternative names: Aloe vera, Aloe barbadensis, Aloe ferox , Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Bupleurum Alternative names: Bupleurum chinense, Bupleurum falcatum Source: Healthnotes, Inc.; www.healthnotes.com Caraway Alternative names: Carum carvi Source: Healthnotes, Inc.; www.healthnotes.com Chamomile Alternative names: Matricaria recutita Source: Healthnotes, Inc.; www.healthnotes.com Chamomile Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,766,00.html Coleus Forskohlii Source: Prima Communications, Inc.www.personalhealthzone.com Dicyclomine Source: Healthnotes, Inc.; www.healthnotes.com Digestive Enzymes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10051,00.html Fiber Source: Healthnotes, Inc.; www.healthnotes.com FOS Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10026,00.html Ginger Alternative names: Zingiber officinale Source: Healthnotes, Inc.; www.healthnotes.com

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GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: Prima Communications, Inc.www.personalhealthzone.com Grapefruit Seed Extract Source: Healthnotes, Inc.; www.healthnotes.com Herbal Digestive Formula Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10104,00.html Hops Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hyoscyamine Source: Healthnotes, Inc.; www.healthnotes.com Ispaghula Source: Integrative Medicine Communications; www.drkoop.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html L. Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Lactase Source: Healthnotes, Inc.; www.healthnotes.com Lactobacillus Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Marshmallow Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10042,00.html Mentha X Piperita Source: Integrative Medicine Communications; www.drkoop.com

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Peppermint Alternative names: Mentha piperita Source: Healthnotes, Inc.; www.healthnotes.com Peppermint Alternative names: Mentha x piperita Source: Integrative Medicine Communications; www.drkoop.com Peppermint Source: Prima Communications, Inc.www.personalhealthzone.com Peppermint Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,812,00.html Plantago Isphagula Source: Integrative Medicine Communications; www.drkoop.com Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org PMS Herbal Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,947,00.html Psyllium Alternative names: Plantago ovata, Plantago ispaghula Source: Healthnotes, Inc.; www.healthnotes.com Psyllium Alternative names: Ispaghula,Plantago isphagula Source: Integrative Medicine Communications; www.drkoop.com Psyllium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,814,00.html Slippery Elm Source: Prima Communications, Inc.www.personalhealthzone.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Valerian Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca

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Valerian Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10064,00.html Wormwood Alternative names: Artemisia absinthium Source: Healthnotes, Inc.; www.healthnotes.com

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

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

Dissertations on Irritable Bowel Syndrome 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 irritable bowel syndrome. 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: •

A Comparative Psychophysiological Study of Normal Subjects, Psychoneurotic Patients and Patients with Irritable Bowel Syndrome by Latimer, Paul Ross; PhD from McMaster University (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK50847

•

Autonomic and Endocrine Activity in Irritable Bowel Syndrome Patients with and without Depressive Symptoms by Thompson, Jennifer Jean; PhD from The University of Oklahoma Health Sciences Center, 2003, 197 pages http://wwwlib.umi.com/dissertations/fullcit/3087228

•

Irritable Bowel Syndrome among Women with Chronic Pelvic Pain: Characteristics, Treatment, and Post-operative Outcomes by Williams, Rachel Elizabeth; PhD from The University of North Carolina at Chapel Hill, 2003, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3086650

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•

Stress Management Training for the Irritable Bowel Syndrome by Lynch, Patrick Michael; PhD from Queen's University at Kingston (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL32193

•

The Impact of Psychological Information on Medical Recommendations for Treating Irritable Bowel Syndrome by Roth, David Alan; PhD from Hofstra University, 2003, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3075169

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

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CHAPTER 5. CLINICAL TRIALS AND IRRITABLE BOWEL SYNDROME Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning irritable bowel syndrome.

Recent Trials on Irritable Bowel Syndrome The following is a list of recent trials dedicated to irritable bowel syndrome.8 Further information on a trial is available at the Web site indicated. •

Genetics of Fibromyalgia Condition(s): Fibromyalgia; Irritable Bowel Syndrome; Chronic Fatigue Syndrome; Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The Fibromyalgia Family Study identifies and collects blood samples from families with two or more members affected with Fibromyalgia Syndrome (FMS). The primary goal of the study is to identify genes that predispose people to FMS and/or symptoms related to FMS; identifying these genes may lead to a better understanding of the disease and more effective treatments. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071162

•

Study In Women With Severe Diarrhea-Predominant Irritable Bowel Syndrome Having Failed Conventional Therapy Condition(s): Irritable Bowel Syndrome

8

These are listed at www.ClinicalTrials.gov.

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Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: The purpose of this study is to compare the safety and effectiveness of as needed versus fixed dosing of an investigational medication for women with severe diarrhea-predominant Irritable Bowel Syndrome (IBS) who have failed conventional therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067457 •

Study Of Women With Severe Diarrhea-Predominant Irritable Bowel Syndrome Having Failed Conventional Therapy Condition(s): Irritable Bowel Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: The purpose of this study is to compare the safety and effectiveness of different doses of an investigational medication in women with severe diarrheapredominant Irritable Bowel Syndrome (IBS) who have failed conventional therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067561

•

Acupuncture vs. Placebo in Irritable Bowel Syndrome Condition(s): Irritable Bowel Syndrome Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: Little is known about acupuncture's efficacy for Irritable Bowel Syndrome (IBS). This trial uses a manualized acupuncture treatment format that closely follows clinical practice and allows flexibility in designing individualized treatments. In addition, a second parallel qualitative study will follow a subgroup of patients throughout the trial to explore the relationships between patients' interpretations and understandings (what anthropologists call "meaning") of irritable bowel and their response to treatment. Cortisol levels (an important stress hormone) will also be assessed. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065403

•

Brain Imaging and Pain in Irritable Bowel Syndrome Condition(s): Irritable Bowel Syndrome

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Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study examines the mechanisms, including brain imaging of placebo analgesia Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065754 •

Treatment of Functional Bowel Disorders Condition(s): Irritable Bowel Syndrome; Constipation; Abdominal Pain; Functional Colonic Diseases Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The primary purpose for this study is to compare clinical treatments for patients with functional bowel disorders (irritable bowel syndrome, abdominal pain, painful constipation) in women. We also plan to: 1) determine what clinical features (medical or psychological) determine which patients will improve to these treatments, and 2) understand if there are any physiological features that relate to improvement in symptoms and response to the treatments. We will compare a psychological treatment (cognitive-behavioral therapy - CBT) with education/attention placebo, and an antidepressant drug (desipramine) with a pill placebo. This is the first large-scale study designed to determine the therapeutic effects of these methods, and to also determine interactions among physiologic measures, psychologic and sociodemographic factors, severity of symptoms, and therapeutic improvement including quality of life. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006157

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 “irritable bowel syndrome” (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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 6. PATENTS ON IRRITABLE BOWEL SYNDROME Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “irritable bowel syndrome” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on irritable bowel syndrome, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Irritable Bowel Syndrome By performing a patent search focusing on irritable bowel syndrome, 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. 9Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on irritable bowel syndrome: •

1-substituted-1-aminomethyl-cycloalkane derivatives (=gabapentin analogues), their preparation and their use in the treatment of neurological disorders Inventor(s): Bryans; Justin Stephen (Balsham, GB), Capiris; Thomas (Plymouth, MI), Horwell; David Christopher (Cambridge, GB), Kneen; Clare Octavia (Essex, GB), Wustrow; David Juergen (Ann Arbor, MI) Assignee(s): Pfizer, Inc. (Ann Arbor, MI) Patent Number: 6,518,289 Date filed: April 3, 2000 Abstract: Novel amines of formulas (1), (1C), (1F), (1G) and (1H) or a pharmaceutical acceptable salt thereof wherein n is an integer of from 0 to 2; m is an integer of from 0 to 3; R is sulfonamide, amide, phosphonic acid, heterocycle, sulfonic acid, or hydroxamic acid; A' is a bridged ring selected from (1), (2), (3), (4), (5) wherein is the point of attachment; Z.sub.1 to Z.sub.4 are each independently selected from hydrogen and methyl; o is an integer of from 1 to 4; and p is an integer of from 0 to 2. In formula (1) above R cannot be sulfonic acid when m is 2 and n is 1 are disclosed and are useful as agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, especially irritable bowel syndrome. Excerpt(s): wherein R.sub.1 is a straight or branched alkyl group having from 1 to 6 carbon atoms, phenyl, or cycloalkyl having from 3 to 6 carbon atoms; R.sub.2 is hydrogen or methyl; and R.sub.3 is hydrogen, methyl, or carboxyl are known in U.S. Pat. No. 5,563,175 and various divisionals. These patents are hereby incorporated by reference. The compounds of the instant invention are novel amines and their pharmaceutically acceptable salts useful in a variety of disorders. The disorders include: epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, inflammatory diseases, and gastrointestinal disorders, especially irritable bowel syndrome. The compounds of the invention are those of formulas 1, 1C, 1F, 1G, and 1H below. Web site: http://www.delphion.com/details?pn=US06518289__

•

Administering osmotic colonic evacuant containing a picosulfate Inventor(s): Borody; Thomas Julius (144 Great North Road, Five Dock NSW 2046, AU), Shortis; Nicolas Peter (144 Great North Road, Five Dock NSW 2046, AU), Shortis; Walter George (144 Great North Road, Five Dock NSW 2046, AU) Assignee(s): none reported Patent Number: 6,103,268 Date filed: November 30, 1998 Abstract: Colonic evacuation, treatment of small bowel bacterial overgrowth or irritable bowel syndrome or treating acute or chronic bacterial bowel infection comprises administering an osmotic colonic evacuant in solid form, preferably a mixture of sodium dihydrogen phosphate and disodium hydrogen phosphate or a sulfate based laxative comprising a picosulfate, together with a diluent.

Patents 135

Excerpt(s): The present invention relates to orthostatic lavage solutions or colonic evacuants for cleansing the gastrointestinal tract, or for the treatment of bowel diseases and/or disorders. The advent of colonoscopy brought with it the need for a simplified, routine bowel cleansing protocol or product to achieve a clean colonic mucosa required by the colonoscopist to detect even small lesions in the bowel, e.g., small polyps. Similar requirements exist for colonic surgery. In the early days of colonoscopy, during the late 1970's, numerous protocols for bowel cleansing were designed by individual bowel surgeons and gastroenterologists to satisfy the requirements of their particular practices. Such protocols included the use of fasting in combination with various purgatives such as Epsom salts or osmotic agents plus enemas. Though, when complex protocols were followed strictly they often achieved their effect and resulted in a clean bowel. However, the protocols were invariably complex and required on average three days of cleansing which made them unpleasant and unacceptable. Furthermore, they were often dangerous because they caused marked fluid and electrolyte shifts in body compartments and on rare occasions predisposed to arrythmias, hypertension and in fact demise of the patient. Web site: http://www.delphion.com/details?pn=US06103268__ •

Arylcycloalkane carboxylic esters, their use, pharmaceutical compositions and preparation Inventor(s):.ANG.kerblom; Eva (Uppsala, SE), Beierlein; Katarina (Uppsala, SE), Haraldsson; Martin (Taby, SE), Johansson; Rolf (Huddinge, SE), Ringberg; Erik (Uppsala, SE), Sjoberg; Birger (Sollentuna, SE), Weinz; Birgitta (Sollentuna, SE) Assignee(s): Pharmacia & Upjohn AB (Stockholm, SE) Patent Number: 6,124,354 Date filed: April 12, 1999 Abstract: This invention relates to the use of 2-(diisopropylamino)-ethyl-1-phenylcyclopentane-carboxylate or 2-(diisopropylamino)-ethyl-1-phenyl-cyclohexanecarboxylate, or a pharmaceutically accceptable salt thereof, for treatment of urinary incontinence or irritable bowel syndrome (IBS). Excerpt(s): The present invention relates to arylcycloalkane carboxylic esters having pharmacological properties, and to processes for their preparation. The invention also relates to pharmaceutical compositions containing arylcycloalkane carboxylic esters, methods of treating disorders related to urinary incontinence and irritable bowel syndrome (IBS), respectively, by administering an arylcycloalkane carboxylic ester, as well as methods for the manufacture of pharmaceutical compositions for treating disorders related to urinary incontinence and irritable bowel syndrome (IBS), respectively. A number of arylcycloalkane carboxylic esters, including arylcyclopropane, arylcyclobutane, arylcyclopentane and arylcyclohexane carboxylic acid esters, are known to possess anticholinergic activity. Some of them have a pronounced spasmolytic or anticonvulsant activity and have therefore been proposed to be used as substitutes for atropine in the treatment of sarin poisoning (sarin is an organophosphorous anticholinesterase agent acting as a nerve gas). Other activities related to that type of compounds are antipsychotic, anti-ischemic, anti-stroke and antidementia. Specific arylcyclopropane carboxylic esters having anticholinergic activities are, for example, described in Beres, J. A., et al., J. Pa. Acad. Sci. (1992), 66(1), 2; U.S. Pat. No. 4,418,202; Mnjoyan, A. L., et al., Arm. Khim. Zh. (1976), 29(2) 194-9; Kuzuna, S., et al., Takeda Kenyosho Hu (1975), 34(4), 467-73; and WO 92/02481.

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Web site: http://www.delphion.com/details?pn=US06124354__ •

Bis (benzimidazole) derivatives serving as potassium blocking agents Inventor(s): Jensen; Bo Skaaning (Copenhagen S, DK), Olesen; S.o slashed.ren Peter (Klampenborg, DK), Peters; Dan (Arlov, DK), Str.o slashed.b.ae butted.k; Dorte (Farum, DK), Teuber; Lene (V.ae butted.rl.o slashed.se, DK) Assignee(s): Neurosearch A/S (Ballerup, DK) Patent Number: 6,194,447 Date filed: July 2, 1999 Abstract: This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions.Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Excerpt(s): This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Ion channels are transmembrane proteins, which catalyze the transport of inorganic ions across cell membranes. The ion channels participate in processes as diverse as the generation and timing of action potentials, synaptic transmissions, secretion of hormones, contraction of muscles, etc. Web site: http://www.delphion.com/details?pn=US06194447__

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•

Dietary supplement and method for use as a probiotic, for alleviating the symptons associated with irritable bowel syndrome Inventor(s): Perry; Stephen C. (205 Churchill Dr., Longwood, FL 32779) Assignee(s): none reported Patent Number: 6,203,797 Date filed: January 7, 2000 Abstract: A dietary supplement for use as a probiotic and for alleviating symptoms of irritable bowel syndrome, comprising freeze-dried aloe, fructo-oligosaccharides, and dahlia inulin juice mixture and optionally vitamin B6 (pyridoxine) manganese and Lglutamine. An additional alternate embodiments specifically for alleviation of symptoms of irritable bowel syndrome, including in the base formula bromelain and papain. Also for specific probiotic functions the following friendly bacteria: Lactobacillus bulgaricus, lactobacillus acidophilus, lactobacillus plantarum, and Bifidobacterium bifidum could be added to the base formula. Excerpt(s): Not applicable. The present invention relates to a dietary supplement and method for use as a probiotic(immuno-stimulant) and for alleviating the symptoms associated with irritable bowel syndrome. The use of dietary supplements for alleviating specific symptoms associated with particular human health problems is well known. Going back to ancient times, references are made to various dietary foods, herbs, and other naturally produced substances that are associated with improving the human health condition. Web site: http://www.delphion.com/details?pn=US06203797__

•

Method and apparatus for diagnosis of irritable bowel syndrome Inventor(s): Craine; Brian L. (Fairfax, CA) Assignee(s): Western Research Company, Inc. (Tucson, AZ) Patent Number: 6,228,040 Date filed: July 28, 1999 Abstract: A protocol for the recording of bowel sounds, a computerized algorithm for recognizing the start and stop time of bowel sounds in the digital sound recordings, metrics that can be calculated from the start and stop times and limits of these metrics which can be used to categorize individuals with respect to medical conditions which effect the gastrointestinal tract. The use of these methods and values allows for the diagnosis of certain gastrointestinal syndromes or diseases with a high degree of accuracy in a manner not previously possible. Excerpt(s): The invention relates to using a computerized analysis of bowel sounds recorded using an electronic sound input device to diagnose gastrointestinal complaints of pain, bloating, or alteration of bowel habits, with emphasis on the diagnosis of irritable bowel syndrome. Irritable bowel syndrome is characterized by bowel irregularity (constipation and/or diarrhea), gaseous distention and abdominal pain. Irritable bowel syndrome is the most common gastrointestinal complaint for which patients seek medical care, accounting for 30 to 50 percent of the gastrointestinal complaints that bring patients to a physician. Various studies indicate that patients with irritable bowel syndrome constitute a large portion of a typical family physician's practice and account for more than 25% of all gastrointestinal referrals. Irritable bowel

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syndrome is listed as a primary diagnosis in about 96,000 patients per year treated in nonfederal hospitals, and the disorder was considered a secondary diagnosis in another 85,000 patients. Most patients with gastrointestinal complaints are subjected to a battery of laboratory studies. These usually include sigmoidoscopy, complete blood count, erythrocyte sedimentation rate, serum electrolytes, liver function tests, urinalysis, and stool examination for occult blood and parasites. For a patient with chronic or recurring symptoms, endoscopy or radiographic contrast evaluations can be performed (but should not be repeated unless there is objective evidence of a change in the clinical condition, such as blood in the stool). In western societies, irritable bowel syndrome occurs twice as often in women as in men. About half of the patients are first seen for this condition before they reach 35 years of age. Various studies indicate that almost half of the patients are between the ages of 35 and 49, although symptoms usually begin much earlier and are likely to continue throughout life. The true prevalence of irritable bowel syndrome may be reflected in several non-patient surveys in which as much as 20 percent of the general population reported symptoms consistent with this disorder. The majority of these people do not seek medical assistance, although it is possible that their symptoms could be alleviated through education, simple methods of stress reduction, and dietary changes. Web site: http://www.delphion.com/details?pn=US06228040__ •

Method and composition for treating irritable bowel syndrome using low doses of opioid receptor antagonists Inventor(s): Crain; Stanley M. (Leonia, NJ), Fleischner; Gerald M. (Chappaqua, NY), Shen; Ke-fei (Flushing, NY) Assignee(s): Albert Einstein College of Medicine of Yeshiva University (Bronx, NY) Patent Number: 6,194,382 Date filed: March 3, 1999 Abstract: This invention relates to a method for eating a subject with irritable bowel syndrome ("IBS") which comprises long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system ("CNS"). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a subject with IBS, which comprises an effective dose of an opioid receptor antagonist, and a pharmaceutically acceptable carrier. Excerpt(s): This invention relates to a method for treating a subject with irritable bowel syndrome ("IBS") which comprises administering a low dose of an opioid receptor antagonist to the subject. Specifically, this invention relates to a method for treating a subject with IBS by the long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system ("CNS"). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from

Patents 139

abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a subject with IBS, which comprises an effective dose of an opioid receptor antagonist, and a pharmaceutically acceptable carrier. Irritable bowel syndrome is a functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit. IBS has elements of an intestinal motility disorder, a visceral sensation disorder, and a central nervous disorder. While the symptoms of IBS have a physiological basis, no physiological mechanism unique to IBS has been identified. Rather, the same mechanisms that cause occasional abdominal discomfort in healthy individuals operate to produce the symptoms of IBS. The symptoms of IBS are therefore a product of quantitative differences in the motor reactivity of the intestinal tract, and increased sensitivity to stimuli or spontaneous contractions. Due to a lack of readily identifiable structural or biochemical abnormalities in this syndrome, the medical community has developed a consensus definition and criteria, known as the Rome criteria, to aid in diagnosis of IBS. According to the Rome criteria, IBS is indicated by abdominal pain or discomfort which is (1) relieved by defection and/or (2) associated with a change in frequency or consistency of stools, plus two or more of the following: altered stool frequency, altered stool form, altered stool passage, passage of mucus, and bloating or feeling of abdominal distention (Dalton, C. and Drossman, D. A., Am Fam Physician 1997 55(3):875-880). Thus, a hallmark of IBS is abdominal pain that is relieved by defecation, and which is associated with a change in the consistency or frequency of stools. IBS may be diarrhea-predominant, constipationpredominant, or an alternating combination of both. Web site: http://www.delphion.com/details?pn=US06194382__ •

Method for alleviation of lower gastrointestinal disorders in a human patient Inventor(s): Dave; Bhavin (262 Pine Valley Dr., Dover, DE 19904), Rubin; Walter (1708 Riverview Rd., Gladwyne, PA 19035) Assignee(s): none reported Patent Number: 6,156,771 Date filed: May 21, 1998 Abstract: A method of alleviating a lower GI symptom in a human patient afflicted with a lower GI disorder and a method of treating a human patient afflicted with a lower GI disorder, including, for example, a patient afflicted with irritable bowel syndrome or a patient afflicted with functional diarrhea, are provided. Each of these methods comprises inhibiting gastric secretion by the patient, such as by administering to the patient a pharmaceutical preparation comprising an effective amount of an inhibitor of gastric secretion. Excerpt(s): The field of the invention is alleviation of lower gastrointestinal (GI) disorders in a human patient and alleviation of lower GI symptoms associated with such disorders. Between about 5% and about 10% of the U.S. population suffers from chronic diarrhea for which an organic cause cannot be identified (Camilleri et al., 1977, Aliment Pharmacol Ther. 11:3-15; Talley et al., 1991, Gastroenterology 101:927-934). The diarrhea may be persistent or may alternate with periods of normal bowel habit or with periods of constipation. Chronic diarrhea which is not accompanied by abdominal. pain and which is not attributable to an organic cause is referred to as "functional diarrhea" (FD) or "chronic idiopathic diarrhea" (Drossman et al., 1997, Gastroenterology 112:21202137; Hasler et al., 1995, In: Textbook of Gastroenterology, 2nd ed., Yamada, Ed., J. B. Lippincott Co., Philadelphia, pp. 1832-1855; Camilleri et al., supra; Drossman et al., 1994,

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The functional Gastrointestinal disorders: Diagnosis, Pathophysiology, and Treatment, Degnon and Associates, McLean, Va.; Thompson et al., 1992, Gastroenterol. Intl. 5:7591). Chronic diarrhea which is associated with abdominal pain and which is not attributable to an organic cause is referred to as "irritable bowel syndrome with a diarrhea predominance" (IBS; Hasler et al., supra; American Gastroenterological Association, 1997, Gastroenterol. 112:2118-2119; Drossman et al., 1997, Gastroenterol. 112:2120-2137; Camilleri et al., supra). Postprandial urgency or postprandial accentuation of lower GI symptoms are common manifestations of both IBS and FD. Patients afflicted with either IBS or FD frequently experience an urgency to defecate after eating, and sometimes attribute this urgency to the ingestion of particular foods other than lactose. Furthermore, some of these patients associate exacerbation of their symptoms with emotional stress. These symptoms have led investigators of IBS and FD to believe that abnormal physiological factors, psychological factors, or both, may be associated with IBS and FD (Drossman et al., supra; Hasler et al., supra; Camilleri et al., supra; Drossman et al., supra; Drossman et al., supra; O'Brien et al., 1996, Gastroenterol. Clin. N. Am. 25:147-162; Bazzocchi et al., 1991, Gastroenterology 101:1298-1306; Choi et al., 1997, Am. J. Gastroenterol. 92:297-306; Aggarwal et al., 1994, Gastroenterology 106:945-950; Quigley, 1996, Gastroenterol. Clin. N. Am. 25:113-145; Schmidt et al., 1996, Scand. J. Gastroenterol. 31:581-589; Evans et al., 1996, Gastroenterology 110:393-404; Gorard et al., 1994, Gut 35:203; Kellow et al., 1990, Gastroenterology 98:1208; Whitehead, 1996, Gastroenterol. Clin. N. Am. 25:21-34). No effective therapy has been established for the chronic diarrhea or the postprandial urgency associated with either IBS or FD (Drossman et al., 1997, supra; Hasler et al., supra; Camilleri et al., supra; Drossman et al., 1994, supra; Thompson et al., supra; Klein, 1988 Gastroenterology 95:232-241). Web site: http://www.delphion.com/details?pn=US06156771__ •

Method of collagen therapy using relaxin Inventor(s): Yue; Samuel K. (4928 Hoppy La., Edina, MN 55435) Assignee(s): none reported Patent Number: 6,048,544 Date filed: November 19, 1998 Abstract: A method of treating involuntary muscle dysfunctions includes administering a therapeuticaly effective amount of relaxin to a patient. Involuntary muscle dysfunctions amenable to treatment with relaxin include fibromyalgia, myofascial pain syndrome, chronic fatigue syndrome, dystonia, pelvic floor dysfunction, irritable bowel syndrome, and others. Excerpt(s): The present invention relates to the treatment of involuntary muscle dysfunctions. In particular, the present invention relates to the treatment of involuntary muscle dysfunction with relaxin hormone. Involuntary muscle dysfunction plagues a large portion of the chronic pain and chronic fatigue patient population. Two prominent conditions involving involuntary muscle dysfunction include fibromyalgia and myofascial pain syndrome, amongst others. Fibromyalgia is identified by the main symptoms of generalized chronic pain occurring mainly in the muscles and hyperalgesia, i.e. multiple tender points spread out over the body. The full range of symptoms include generalized pain, hyperalgesia, sleep disturbance, fatigue, muscle stiffness, hypersthesias, tension-type headaches, decreased muscle endurance and muscle weakness. Fibromyaglia has also been associated with irritable bowel syndrome, chronic fatigue syndrome, temporomandibular dysfunction syndrome,

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migraines, primary dysmenhorrea (painful menstruation) and others conditions including Raynaud's phenomenon. See Yunnus, Fibromyalgia Syndrome: Clinical Features and Spectrum, The Fibromyalgic Syndrome: Current Research and Future Directions in Epidemiology, Pathogenesis, and Treatment, 1994, pp. 5-21. See also Wolfe, When to Diagnose Fibromyalgia, Rheumatic Disease Clinics Of North America, Vol. 20, Number 2, May 1994. See Henriksson, Pathogenesis of Fibromyalgia, Journal of Musculoskeletal Pain, 1993, Vol. 1, pp. 3-16. Web site: http://www.delphion.com/details?pn=US06048544__ •

METHOD OF DIAGNOSING IRRITABLE BOWEL SYNDROME AND OTHER DISORDERS CAUSED BY SMALL INTESTINAL BACTERIAL OVERGROWTH BY DETECTING THE PRESENCE OF ANTI-SACCHAROMYCES CERIVISIAE ANTIBODIES (ASCA) IN HUMAN SERUM Inventor(s): Lin; Henry C. (Manhattan Beach, CA), Pimentel; Mark (Los Angeles, CA) Assignee(s): Cedars-Sinai Medical Center (Los Angeles, CA) Patent Number: 6,562,629 Date filed: August 11, 1999 Abstract: Disclosed is a method of diagnosing small intestinal bacterial overgrowth (SIBO), irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, attention deficit/hyperactivity disorder (ADHD), or an autoimmune disease by sampling serum from a human subject having a suspected diagnosis of any of these conditions and analyzing the serum for the presence of ASCA, which corroborates the suspected diagnosis. A method of determining a predisposition for developing Crohn's, in a human subject who does not present a set of symptoms characteristic of the disease and who has small intestinal bacterial overgrowth, involves sampling serum from the subject and analyzing the serum for the presence of ASCA. The presence of ASCA in the serum indicates a predisposition for developing Crohn's disease. Also disclosed is a kit for diagnosing and treating small intestinal bacterial overgrowth, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, attention deficit/hyperactivity disorder, or an autoimmune disease, such as multiple sclerosis or systemic lupus erythematosus. The kit is useful to improve symptoms, including hyperalgesia related to SIBO and disorders caused by SIBO. Excerpt(s): Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. This invention relates to the medical arts. It relates to a method of diagnosing or treating small intestinal bacterial overgrowth, irritable bowel syndrome and other disorders, such as Crohn's disease, chronic fatigue syndrome, fibromyalgia, depression, attention deficit/hyperactivity disorder, multiple sclerosis, systemic lupus erythematosus and other auto immune diseases in a human subject. Irritable bowel syndrome, Crohn's disease, chronic fatigue syndrome, fibromyalgia, depression, attention deficit/hyperactivity disorder, and autoimmune diseases, e.g., multiple sclerosis and systemic lupus erythematosus, are all clinical conditions of unclear etiology. Web site: http://www.delphion.com/details?pn=US06562629__

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Method of screening for compounds that bind P2x receptor Inventor(s): Buell; Gary N (Geneva, CH), Valera; Soledad (Geneva, CH) Assignee(s): Glaxo Group Limited (Greenford, GB) Patent Number: 6,194,162 Date filed: July 30, 1999 Abstract: The P.sub.2X receptor of ATP has been cloned and expressed by recombinant DNA technology, so the receptor can be prepared free from other ATP receptors. The P.sub.2X receptor enables antibodies to be prepared and is useful in screening compounds for use in a variety of diseases and conditions, including epilepsy, cognition, emesis, pain (especially migraine), asthma, peripheral vascular disease, hypertension, diseases of the immune system, irritable bowel syndrome and premature ejaculation. Excerpt(s): This invention relate to the P.sub.2X -purinoceptor, its preparation and uses. The P.sub.2X -purinoceptor is a ligand-gated ion channel; that is, the receptor itself forms an ion channel which opens when extracellular adenosine 5'-triphosphate (ATP) binds to the receptor. There are five other classes of neurotransmitter receptors (nicotinic acetylcholine, glutamate, glycine, GABA.sub.A and 5-HT.sub.3); these form a structurally related superfamily of ligand-gated ion channels (Barnard, Trends Biochem. Sci. 17, 368-374, (1992)). The P.sub.2X -receptor now identifies a new family of this type of receptor. The unique structure of this receptor, the widespread distribution of this receptor throughout the body, and the numerous physiological roles this receptor may play, make it an important protein that can be used to identify new, therapeutically effective, compounds for the treatment of a number of pathological states. In 1929 the eminent physiologist Szent-Gyorgyi described powerful cardiovascular actions of extracellular purine nucleosides (e.g. adenosine) and nucleotides (e.g. ATP) (Drury & Szent-Gyorgyi, J. Physiol. 68 213-237 (1929)), but it was not until 1972 that pharmacological evidence was provided to suggest the existence of distinct receptors for extracellular ATP (ie. that recognise ATP but not adenosine) (Burnstock, Pharmacological Reviews 21 509-581 (1972)). The seminal and subsequent work on this area by Burnstock and colleagues was largely unaccepted throughout the 1970s and early 1980s until the development of a range of relatively selective ligands and techniques for directly measuring ATP release overwhelmingly substantiated Burnstock's hypothesis (Barnard et al., Trends Pharmacol. Sci. 15 67-70 (1994)). In the past four or five years, unequivocal evidence for the role of ATP as a neurotransmitter has been provided for sympathetic control of blood flow to the intestine and smooth muscle tone (contractility) in genitourinary tissue such as vas deferens, bladder and ureter (Barnard et al. (loc. cit.) and Evans & Surprenant, Brit. J. Pharmacol. 106 242-249 (1992)). Substantial indirect evidence also exists for the role of ATP as a neurotransmitter in a number of distinct neurones in the spinal cord, autonomic ganglia and certain nuclei in the central nervous system (Bean, Trends Pharmacol. Sci. 15 67-70 (1992), Evans et al., Nature 357, 503-505 (1992) and Edwards et al., Nature 359 144-147 (1992)). Web site: http://www.delphion.com/details?pn=US06194162__

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Method of treating irritable bowel syndrome Inventor(s): Dunn; Peter James (Sandwich, GB), Humphrey; Michael John (Sandwich, GB), Quinn; Paul (Sandwich, GB) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,653,339 Date filed: August 13, 2002 Abstract: The present invention is directed to a a method for the treatment of irritable bowel syndrome comprising the multiple daily pulse dosing of an immediate release formulation of the anti-muscarinic darifenacin. Dosing two or three times a day is particularly preferred. Excerpt(s): The present invention is concerned with a method for the treatment of irritable bowel syndrome which involves the multiple daily dosing of an immediate release formulation of the anti-muscarinic darifenacin. Dosing two or three times a day is particularly preferred. Darifenacin is a muscarinic antagonist whose preparation and proposed use in the treatment of diseases associated with altered motility and/or tone of smooth muscle as found, for example, in the gut, trachea and bladder are described in U.S. Pat. No. 5,096,890. Specific diseases referred to include irritable bowel syndrome, diverticular disease, urinary incontinence, oesophageal achalasia and chronic obstructive airways disease. Of these, irritable bowel syndrome and urinary incontinence are particularly attractive targets for a muscarinic antagonist and controlled release formulations of darifenacin intended for use in the treatment of these diseases wherein at least 10% by weight of the darifenacin is released in the lower gastrointestinal tract are the subject of U.S. Pat. No. 6,106,864. The text of these patents and all other references cited in this specification are hereby incorporated by reference in their entirety. Web site: http://www.delphion.com/details?pn=US06653339__

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Methods for treating apnea, apnea disorders, bulimia, and other disorders using optically pure (+) norcisapride Inventor(s): Barberich; Timothy J. (Concord, MA), Rubin; Paul D. (Sudbury, MA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 6,048,879 Date filed: June 14, 1999 Abstract: Methods for the prevention, treatment or management of apnea, apnea disorders, bulimia nervosa, irritable bowel syndrome, urinary incontinence, bradycardia, bradyarrhythmia, syncope, other disorders, or symptoms thereof using (+) norcisapride, or a pharmaceutically acceptable salt thereof, substantially free of its (-) stereoisomer. Excerpt(s): The invention relates to methods of prevention, treatment, or management, of apnea, apnea disorders, bulimia, other disorders, or symptoms thereof. Apnea is defined in Stedman's Medical Dictionary, 26.sup.th Edition, Williams and Wilkins (1995), as the absence of breathing. There are a number of disorders associated with apnea, which are characterized by interrupted breathing in which a person stops breathing long enough to decrease the amount of oxygen and increase the amount of carbon dioxide in the blood and brain. Each type of apnea involves the absence of

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airflow at the nose or the mouth, typically for at least 10 seconds. Various apnea disorders exist, including: central apnea, which results from medullary depression and inhibits respiratory movement; deglutition apnea, which is the inhibition of breathing during swallowing; obstructive or peripheral apnea, which is either a result of obstruction of air passages or inadequate respiratory muscle activity; sleep apnea, which is central and/or obstructive apnea during sleep; and sleep induced apnea, which results from failure of the respiratory center to stimulate adequate respiration during sleep. Web site: http://www.delphion.com/details?pn=US06048879__ •

Methods of modulating muscle contraction Inventor(s): Cote; Graham P. (Kingston, CA), Mak; Alan S. (Kingston, CA), Van Eyk; Jennifer E. (Kingston, CA) Assignee(s): Queen's University at Kingston (Kingston, CA) Patent Number: 6,248,549 Date filed: June 22, 1998 Abstract: Methods of modulating calcium independent smooth muscle contraction, and of modulating cardiac muscle contraction, by the administration of a PAK modulating agent are described. A method of treating a subject having a state characterized by smooth muscle contraction, (e.g., hypertension, asthma, irritable bowel syndrome, incontinence and menstrual cramps) or cardiac contractile dysfunction (e.g., heart failure and myocardial stunning) is also described. The method involves the administration, to a subject, of a therapeutically effective amount of a PAK modulating agent, e.g., a PAK inhibitor or stimulator. Assays, e.g., screening tests, to identify PAK modulating agents or agents that modulate muscle contraction are also provided. Excerpt(s): This invention relates to methods for modulating muscle contraction, and particularly, to methods for modulating smooth muscle contraction in the absence of calcium, and for increasing the calcium sensitivity of both smooth muscle and cardiac muscle. p21-activated kinase (PAK) proteins are serine/threonine protein kinases homologous to the yeast Ste20 kinase. Several distinct members of the PAK family have been identified in mammalian cells, including PAK1, PAK2, PAK3, and PAK65. It has been shown that PAK proteins can be activated by the small Rho-family GTP-binding proteins Cdc42 and Rac1, which are known to regulate assembly of the actin cytoskeletal structure (Zhang et al. 1995, J. Biol. Chem. 270:23934-36). Smooth muscle, in contrast to striated muscle (cardiac and skeletal muscle), is capable of maintaining force at low levels of intracellular calcium. One member of the small Rho-family of GTP-binding proteins, RhoA, has been shown recently to induce smooth muscle contraction independently of calcium. RhoA activates a serinet reonine kinase named ROK (RhoA associated kinase or p160ROK) which can cause smooth muscle calcium-independent contraction. Cardiac muscle, on the other hand, requires increased levels of intracellular calcium for contraction. Web site: http://www.delphion.com/details?pn=US06248549__

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N-substituted pyrrolidine derivatives and process for preparing the same Inventor(s): Ando; Naoki (Nogi-machi, JP), Hoshino; Masato (Oyama, JP), Kobayashi; Fumiyoshi (Oyama, JP), Miyachi; Hiroyuki (Kazo, JP) Assignee(s): Kyorin Pharmaceutical Co., Ltd. (Tokyo, JP) Patent Number: 6,071,950 Date filed: June 2, 1999 Abstract: Novel N-substituted pyrrolidine derivatives having a highly selective and potent antagonism against smooth muscle muscarine receptors and being useful for the treatment of irritable bowel syndrome and the like, characterized by being represented by general formula (1) wherein R represents a hydrogen atom, a halogen atom, or a lower alkoxy group and a process for preparing the same. Excerpt(s): The present invention relates to novel N-substituted pyrrolidine derivatives having a highly selective and potent antagonism against smooth muscle muscarine receptors rather than cardiac muscarine receptors and being useful for the treatment of altered smooth muscle motility and tone, such as irritable bowel syndrome, diverticulosis, urinary incontinence, esophageal achalasia and chronic obstructive airway disease, and process for preparing the same. As one of the therapeutic drugs for the irritable bowel syndrome, the anticholinergic agent has been used, but it brings no sufficient therapeutic effect due to, in part, deficit of tissue selectivity. Also, while compounds that was reported to have a selective antagonism against smooth muscle muscarine receptors are disclosed (Japanese Unexamined Patent Publication Nos. Hei 2282360 and Hei 7-149640, these compounds also do not sufficiently solve the adverse effect such as mydriasis. Moreover, these compounds have diphenylalkyl moiety linked to carbon atom of the pyrrolidine ring, making them different from the structure of the inventive compounds, in which it links to the nitrogen atom of the pyrrolidine ring. The invention is to provide novel N-substituted pyrrolidine derivatives having a highly selective and potent antagonism against smooth muscle muscarine receptors and being useful for the treatment of irritable bowel syndrome and the like. Web site: http://www.delphion.com/details?pn=US06071950__

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Oxazepine derivatives and medicine containing the same Inventor(s): Sakata; Katsutoshi (Kawasaki, JP), Sasaki; Noriko (Kawasaki, JP), Takahashi; Kazuyoshi (Kawasaki, JP), Tsuji; Takashi (Kawasaki, JP) Assignee(s): Ajinomoto Co., Inc. (Tokyo, JP) Patent Number: 6,528,504 Date filed: July 9, 2001 Abstract: The present invention provides (R)-5,11-dihydro-5-[1-(4methoxyphenethyl)piperidine-2-ylmethyl]dibenzo[b, e][1,4]oxazepine, (R)-5,11-dihydro5-[1-(4-dimethylaminophenethyl)piperidine-2-ylmethyl]dibe nzo[b,e][1,4]oxazepine, compounds analogous to them and pharmaceutical compositions containing such a compound. These compounds are useful for treating or preventing abnormal motor functions of gastrointestinal tracts, particularly irritable bowel syndrome. Excerpt(s): The present invention relates to 5,11-dihydrodibenzo [b,e][1,4]oxazepine derivatives antagonistic to calcium channel and useful for treating or preventing abnormal motor functions of gastrointestinal tracts, particularly intestinal diseases such

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as irritable bowel syndrome, stereoisomers thereof, pharmacologically acceptable salts thereof or hydrates thereof, and pharmaceutical compositions containing them as active ingredients. It is disclosed in, for example, European Patent No. 0404359A1 that 5,11dihydrodibenzo[b,e][1,4]thiazepine derivatives are usable as calcium channel antagonists selectively effective on gastrointestinal tracts. Quinn, P. et al., Brit. J. Pharmacol. 1994, 112 (Suppl.), Abst 573P and Wallis R. M. et al. Brit. J. Pharmacol. 1994, 112 (Suppl.), Abst. 574P disclose that (S)-5-[[1-(4-methoxyphenyl)ethyl]pyrrolidine-2ylmethyl]-5,11-dihydrodiben zo[b,e][1,4]thiazepine maleate which is one of derivatives of those compounds has effects similar to the effects of them. Further, International Patent No. 9733885A1 discloses 5-(2-pyrrolidinyl-methyl)-5,11-dihydrodibenzo [b,e][1,4]oxazepine derivatives as medicines for improving motor insufficiency of gastrointestinal tracts. However, the activity and selectivity of these compounds toward gastrointestinal tracts are yet insufficient, and another defect of them is that they have an anticholinergic effect which causes side effects such as thirstiness and mydriasis. As social environments have been complicated recently, many of people feel the severe stress and patients with irritative bowel syndrome having cardinal symptoms of irregular bowel movement and abdominal pain are increasing in number. Medicines used for improving these diseases are, for example, cholinergic blocking agents, laxatives, antidiarrheal agents, intestinal drugs, mucosal paralyzers, gastrointestinal function regulators, autonomic nerve regulators, Chinese medicines, anxiolytic agents, antidepressant agents, sleep promoting drugs and neurotropic agents. However, the clinical effects of these medicines are yet insufficient and, in addition, they are not always satisfactory from the viewpoint of side effects of them. Under these circumstances, the development of medicines of a new type for improving the gastrointestinal function regulators, which have no side effect, is demanded. Web site: http://www.delphion.com/details?pn=US06528504__ •

Pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome and new use of substances therein Inventor(s): Efendic; Suad (Stjarnvagen 16B, 18134 Lidingo, SE), Hellstrom; Per (Svardsjovagen 1, 16775 Bromma, SE) Assignee(s): none reported Patent Number: 6,348,447 Date filed: February 3, 2000 Abstract: The invention relates to the new use of gastrointestinal peptide hormones selected from the class consisting of glucagon-like peptide-1 (GLP-1) and derivatives thereof having anti-secretory effects and smooth muscle relaxatory properties in the gastrointestinal tract for the manufacture of a pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome. The invention also relates to a pharmaceutical composition comprising a combination of at least one member selected from said class consisting of GLP-1 and derivatives thereof with one or more other gastrointestinal peptide hormone(s) or derivative(s) thereof together with pharmacologically acceptable additives and to a method of treating functional dyspepsia or irritable bowel syndrome or both by administering an effective amount of at least one member of said class consisting of GLP-1 and derivatives thereof having effects and properties as mentioned above. Excerpt(s): This application is a 371 of PCT/SE99/00997 filed Jun. 8, 1999 which claims priority to Swedish application 98 02080-3 filed Jun. 11, 1998. The present invention

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relates to a new use of a gastrointestinal peptide hormone or a derivative thereof, to a pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome, and to a method for such treatment. Functional diseases are characterized by disordered function of the organ or organ system and no obvious structural pathology can be detected neither macroscopically nor microscopically. This should be differentiated from morphologic pathological diseases where the structure of the organ is changed from normality to abnormality. This type of disease can always be diagnosed either macro- or microscopically, and may be followed by functional aberration of the organ. Web site: http://www.delphion.com/details?pn=US06348447__ •

Smooth muscle spasmolytic agents, compositions and methods of use thereof Inventor(s): Aberg; A. K. Gunnar (Sarasota, FL), Chen; Jan L. (Worcester, MA), Wright; George E. (Worcester, MA) Assignee(s): Bridge Pharma, Inc. (Sarasota, FL) Patent Number: 6,207,852 Date filed: December 23, 1998 Abstract: The present invention relates to smooth muscle spasmolytic agents, pharmaceutical compositions containing them and method of using said compounds and compositions for the treatment of urinary incontinence, gastric hyperactivity (ex. Irritable Bowel Syndrome) and other smooth muscle contractile conditions.More particularly, the present invention relates to certain substituted esters, amides and ketones having smooth muscle relaxing properties while avoiding, on administration to a mammal, adverse side effects such as prominent antimuscarinic, arrhythmogenic and cardiodepressive effects. Excerpt(s): This application is a 371 of PCT/US97/11310 filed Jun. 30, 1997. More particularly, the present invention relates to certain substituted esters, amides and ketones having smooth muscle relaxing properties while avoiding, on administration to a mammal, adverse side effects such as prominent antimuscarinic, arrhythmogenic and cardiodepressive effects. Web site: http://www.delphion.com/details?pn=US06207852__

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Substituted pyridines useful as modulators of acetylcholine receptors Inventor(s): Cosford; Nicholas D. (San Diego, CA), Vernier; Jean-Michel (San Diego, CA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,194,581 Date filed: December 22, 1998 Abstract: In accordance with the present invention, there is provided a class of pyridine compounds which are modulators of acetylcholine receptors. The compounds of the invention displace acetylcholine receptor ligands from their binding sites. Invention compounds may act as agonists, partial agonists, antagonists or allosteric modulators of acetylcholine receptors, and are useful for a variety of therapeutic applications, such as the treatment of Alzheimer's disease and other disorders involving memory loss and/or dementia (including AIDS dementia); disorders of attention and focus (such as attention

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deficit disorder); disorders of extrapyramidal motor function such as Parkinson's disease, Huntington's disease, Gilles de la Tourette syndrome and tardive dyskinesia; mood and emotional disorders such as depression, panic, anxiety and psychosis; substance abuse including withdrawal syndromes and substitution therapy; neuroendocrine disorders and dysregulation of food intake, including bulimia and anorexia; disorders of nociception and control of pain; autonomic disorders including dysfunction of gastrointestinal motility and function such as inflammatory bowel disease, irritable bowel syndrome, diarrhea, constipation, gastric acid secretion and ulcers; pheochromocytoma; cardiovascular dysfunction including hypertension and cardia arrhythmias, comedication in surgical procedures, and the like. Excerpt(s): The present invention relates to novel compounds which are capable of modulating acetylcholine receptors. Invention compounds are useful, for example, for treatment of dysfunction of the central or autonomic nervous systems including dementia, cognitive disorders, neurodegenerative disorders, extrapyramidal disorders, convulsive disorders, cardiovascular disorders, endocrine disorders, pain, gastrointestinal disorders, eating disorders, affective disorders, and drug abuse. In addition, the present invention relates to pharmaceutical compositions containing these compounds, as well as various uses therefor. By modulation of neurotransmitter release (including dopamine, norepinephrine, acetylcholine and serotonin) from different brain regions, acetylcholine receptors are involved in the modulation of neuroendocrine function, respiration, mood, motor control and function, focus and attention, concentration, memory and cognition, and the mechanisms of substance abuse. Ligands for acetylcholine receptors have been demonstrated to have effects on attention, cognition, appetite, substance abuse, memory, extrapyramidal function, cardiovascular function, pain and gastrointestinal motility and function. The distribution of acetylcholine receptors that bind nicotine, i.e., nicotinic acetylcholine receptors, is widespread in the brain, including the basal ganglia, limbic system, cerebral cortex and mid- and hind-brain nuclei. In the periphery, the distribution includes muscle, autonomic ganglia, the gastrointestinal tract and the cardiovascular system. Acetylcholine receptors have been shown to be decreased, inter alia, in the brains of patients suffering from Alzheimer's disease or Parkinson's disease, diseases associated with dementia, motor dysfunction and cognitive impairment. Such correlations between acetylcholine receptors and nervous system disorders suggest that compounds that modulate acetylcholine receptors will have beneficial therapeutic effects for many human nervous system disorders. Thus, there is a continuing need for compounds which can selectively modulate the activity of acetylcholine receptors. In response to such need, the present invention provides a new family of compounds which modulate acetylcholine receptors. Web site: http://www.delphion.com/details?pn=US06194581__ •

Therapeutically active compositions Inventor(s): Gardiner; Fiona Kate (Beverley, GB) Assignee(s): Reckitt & Colman Products Limited (Windsor, GB) Patent Number: 6,201,014 Date filed: December 7, 1999 Abstract: A pharmaceutical composition for the treatment of irritable bowel syndrome, diarrhoea, constipation, abdominal pain and/or bloating or abdominal distension, the composition including a carrier vehicle and a vanilloid compound. The carrier vehicle

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enables the vanilloid compound to be released in the lower gastrointestinal tract. The vanilloid compound has the effect of desensitizing nerves in the lower gastrointestinal tract, thereby leading to symptomatic relief. Preferred vanilloid compounds are capsaicin and resiniferatoxin. Excerpt(s): The present invention relates to compositions for the treatment of irritable bowel syndrome (IBS) and more particularly to locally acting compositions which are active in the post-stomach region of the gastro-intestinal (GI) tract. Irritable Bowel Syndrome (IBS) is part of a spectrum of diseases known generally as Functional Gastrointestinal Disorders which include diseases such as non-cardiac chest pain, nonulcer dyspepsia, and chronic constipation or diarrhoea. These diseases are all characterised by chronic or recurrent gastrointestinal symptoms for which no structural or biochemical cause can be found. Irritable bowel syndrome in the UK alone is responsible for 30-50% of all gastroenterology referrals to secondary care. 2. two or more of the following on at least a quarter of occasions: altered stool frequency, altered stool form, altered stool passage, passage of mucus, and/or bloating or feeling of abdominal distension. Web site: http://www.delphion.com/details?pn=US06201014__ •

Use of orexin receptor antagonists Inventor(s): Irving; Elaine Alison (Bengeo, GB), Sanger; Gareth John (Sawbridgeworth, GB) Assignee(s): SmithKline Beecham p.l.c. (Brentford, GB) Patent Number: 6,506,774 Date filed: November 30, 2001 Abstract: The use of orexin receptor antagonists as neuroprotectants, and in the treatment of nausea and vomiting, irritable bowel syndrome and other conditions associated with visceral pain. Excerpt(s): The present invention relates to the use of orexin receptor antagonists as neuroprotectants, and in the treatment of nausea and vomiting, irritable bowel syndrome and other conditions associated with visceral pain. Many medically significant biological processes are mediated by proteins participating in signal transduction pathways that involve G-proteins and/or second messengers. Polypeptides and polynucleotides encoding the human 7-transmembrane G-protein coupled neuropeptide receptor, orexin-1 (HFGAN72), have been identified and are disclosed in U.S. Pat. Nos. 5,935,814, 6,020,157 and 6,410,701. Polypeptides and polynucleotides encoding a second human orexin receptor, orexin-2 (HFGANP), have been identified and are disclosed in U.S. Pat. No. 6,166,193. Web site: http://www.delphion.com/details?pn=US06506774__

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Use of tropical root crops in effective intervention strategies for treating difficult and complex cases and chronic diseases Inventor(s): Slimak; Karen M. (P.O. Box 2444, Springfield, VA 22152) Assignee(s): none reported Patent Number: 6,632,461 Date filed: July 12, 2001 Abstract: This invention relates to an effective intervention plan. In one aspect, the invention relates to the treatment of various symptoms, conditions or diseases, such as diarrhea, constipation, congestion, eczema, asthma, fatigue, muscle weakness, tension and spasms, irritable bowel syndrome, swelling, anxiety, multiple chemical sensitivities, moderate to excessive and moderate to severe symptoms due to food allergies, sensitivities and intolerances, bloating, pain, headaches, leaky gut, hypersensitivity, sleep difficulties, severe under weight, eating disorders, obsessive, compulsive disorders, panic attacks, sensory sensitivities, Alzheimer's disease, acid refulx, irritability, delayed motor skills, delayed social skills, autism, PDD, infantile spasms and seizures by withholding for a period of at least 5 days all foods except for root crops. Excerpt(s): This invention relates to an effective dietary intervention plan. In one aspect all food is withheld for a period of at least 5 days, except for tropical root crops. In another aspect the invention relates to the treatment of various symptoms, conditions or diseases such as diarrhea, constipation, congestion, eczema, asthma, fatigue, muscle weakness, tension, and spasms, irritable bowel syndrome, swelling, anxiety, multiple chemical sensitivities, moderate to extensive and moderate to severe symptoms due to food allergies, sensitivities, and intolerances, bloating, pain, headaches, leaky gut, hyperactivity, sleeping difficulties, severe underweight, eating disorders, obsessive, compulsive disorders, panic attacks, sensory sensitivities, Alzheimer's disease, acid reflux, irritability, delayed motor skills, delayed social skills, autism, PDD, infantile spasms, seizures by withholding from the patient for a period of at least 5 days all food except for concentrated forms of concentrated tropical root crops. Preferably the patient is also removed from external environmental sources of allergens. After the initial withholding period new foods may be introduced according to a particular selection and schedule. In another aspect of the invention the subject undergoes an effective dietary intervention plan in which at least five (5) tropical root crops are selected, each eaten on a successive day, along with selected other meat, vegetables, and oils that the subject has never eaten before, eating a different selection of meat, vegetables, and oils each from different food families each day, with no food or food family being repeated for at least 5 days. In another aspect the invention relates to the treatment of various symptoms, conditions or diseases such as Diarrhea, constipation, congestion, eczema, asthma, fatigue, muscle weakness, tension, and spasms, irritable bowel syndrome, swelling, anxiety, multiple chemical sensitivities, moderate to extensive and moderate to severe symptoms due to food allergies, sensitivities, and intolerances, bloating, pain, headaches, leaky gut, hyperactivity, sleeping difficulties, severe underweight, eating disorders, obsessive, compulsive disorders, panic attacks, sensory sensitivities, Alzheimer's disease, acid reflux, irritability, delayed motor skills, delayed social skills, autism, PDD, infantile spasms, seizures by withholding from the patient for a period of at least 5 days all food except for concentrated forms of concentrated tropical root crops. Preferably the patient is also removed from external environmental sources of allergens. After the initial withholding period new foods may be introduced according to a particular selection and schedule. In another aspect of the invention the subject

Patents 151

undergoes an effective dietary intervention plan in which at least seven (7) tropical root crops are selected, each eaten on a successive day, along with selected other meat, vegetables, and oils that the subject has never eaten before, eating a different selection of meat, vegetables, and oils each from different food families each day, with no food or food family being repeated for at least 7 days. In another aspect the invention relates to the treatment of various symptoms, conditions or diseases such as Diarrhea, constipation, congestion, eczema, asthma, fatigue, muscle weakness, tension, and spasms, irritable bowel syndrome, swelling, anxiety, multiple chemical sensitivities, moderate to extensive and moderate to severe symptoms due to food allergies, sensitivities, and intolerances, bloating, pain, headaches, leaky gut, hyperactivity, sleeping difficulties, severe underweight, eating disorders, obsessive, compulsive disorders, panic attacks, sensory sensitivities, Alzheimer's disease, acid reflux, irritability, delayed motor skills, delayed social skills, autism, PDD, infantile spasms, seizures by withholding from the patient for a period of at least 5 days all food except for concentrated forms of concentrated tropical root crops. Preferably the patient is also removed from external environmental sources of allergens. After the initial withholding period new foods may be introduced according to a particular selection and schedule. Web site: http://www.delphion.com/details?pn=US06632461__

Patent Applications on Irritable Bowel Syndrome As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to irritable bowel syndrome: •

2-substituted piperidines that are ligands for monoamine receptors and transporters Inventor(s): Aquila, Brian M.; (Marlborough, MA), Hauske, James R.; (Concord, MA) Correspondence: Foley Hoag, Llp; Patent Group, World Trade Center West; 155 Seaport Blvd; Boston; MA; 02110; US Patent Application Number: 20030073681 Date filed: August 6, 2002 Abstract: One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.

10

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

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Excerpt(s): This application claims the benefit of priority to U.S. Provisional Patent Application serial No. 60/313,934, filed Aug. 21, 2001; and U.S. Provisional Patent Application serial No. 60/353,517, filed Jan. 31, 2002. Dopamine, norepinephrine and serotonin are mammalian monoamine neurotransmitters that play important roles in a wide variety of physiological processes. Therefore, compounds that selectively modulate the activity of these three neurotransmitters, either individually, in pairs, or as a group, promise to serve as agents effective in the treatment of a wide range of maladies, conditions and diseases that afflict mammals due to atypical activities of these neurotransmitters. For example, depression is believed to result from dysfunction in the noradrenergic, dopaminergic, or serotonergic systems. Furthermore, the noradrenergic system appears to be associated with increased drive, whereas the serotonergic system relates more to changes in mood. Therefore, it is possible that the different symptoms of depression may benefit from drugs acting mainly on one or the other of these neurotransmitter systems. On the other hand, a single compound that selectively affects both the noradrenergic and serotonergic systems should prove effective in the treatment of depression comprising symptoms related to dysfunction in both systems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

3-Azabicyclo[3.1.0]hexane derivatives useful in therapy Inventor(s): Banks, Bernard Joseph; (County of Kent, GB), Critcher, Douglas James; (County of Kent, GB), Fenwick, Ashley Edward; (County of Kent, GB), Gethin, David Morris; (County of Kent, GB), Gibson, Stephen Paul; (County of Kent, GB) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030207876 Date filed: April 8, 2002 Abstract: Compounds of formula I, 1where the substituents are as defined herein, and the pharmaceutically or veterinarily acceptable derivatives or prodrugs thereof, are pharmaceutically and veterinarily useful, in particular they bind to opiate receptors (e.g. mu, kappa and delta opioid receptors). They are likely to be useful in the treatment of diseases or conditions modulated by opiate receptors, for example irritable bowel syndrome; constipation; nausea; vomiting; pruritic dermatoses, such as allergic dermatitis and atopy; eating disorders; opiate overdoses; depression; smoking and alcohol addiction; sexual dysfunction; shock; stroke; spinal damage; and head trauma. Excerpt(s): This claims application claims priority under 35 U.S.C. 120 of U.S. Ser. No. 09/883,567, filed Jun. 18, 2001. This invention relates to pharmaceutically useful compounds, in particular compounds that bind to opiate receptors (e.g. mu, kappa and delta opioid receptors). Compounds that bind to such receptors are likely to be useful in the treatment of diseases modulated by opiate receptors, for example irritable bowel syndrome; constipation; nausea; vomiting; and pruritic dermatoses, such as allergic dermatitis and atopy in animals and humans. Compounds that bind to opiate receptors have also been indicated in the treatment of eating disorders, opiate overdoses, depression, smoking and alcohol addiction, sexual dysfunction, shock, stroke, spinal damage and head trauma. There is a particular need for an improved treatment of itching. Itching, or pruritus, is a common dermatological symptom that can give rise to considerable distress in both humans and animals. Pruritus is often associated with inflammatory skin diseases which may be caused by hypersensitivity reactions, including reactions to insect bites, such as flea bites, and to environmental allergens,

Patents 153

such as house dust mite or pollen; by bacterial and fungal infections of the skin; or by ectoparasite infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Aminoalkyl substituted 5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole and tetrahydro-9H-pyrimidino[4,5-b]indole derivatives: CRF1 specific ligands

5,6,7,8-

Inventor(s): Darrow, James W.; (Wallingford, CT), Horvath, Raymond F.; (North Branford, CT), Maynard, George D.; (Clinton, CT) Correspondence: Steven J. Sarussi; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030105117 Date filed: August 27, 2002 Abstract: Disclosed are compounds of the formula: 1whereinAr, R.sup.1, W, X and m are substituents as defined herein.These compounds are modulators of CRF receptors and are therefore useful for treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of Formula I. Excerpt(s): The present invention relates to aminoalkyl substituted 5,6,7,8-tetrahydro9H-pyridino[2,3-b]indole and 5,6,7,8-tetrahydro-9H-pyrimidino[4,5-b]indole derivatives, pharmaceutical compositions containing such compounds and their use in treating psychiatric disorders, neurological diseases, immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress. Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (POMC) derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al., Rec. Prog. Horm. Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39 (1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors [J. E. Blalock, Physiological Reviews 69:1 (1989); J. E. Morley, Life Sci. 41:527 (1987)]. Clinical data provide evidence that CRF has a role in psychiatric disorders and neurological diseases including depression, anxiety-related disorders and feeding disorders. A role for CRF has also been postulated in the etiology and pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, progressive supranuclear palsy and

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amyotrophic lateral sclerosis as they relate to the dysfunction of CRF neurons in the central nervous system [for review see E. B. De Souza, Hosp. Practice 23:59 (1988)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Bifidobacterium in the treatment of inflammatory disease Inventor(s): Collins, John Kevin; (Duncloyne, IE), O'Mahony, Liam; (Cork, IE), O'Sullivan, Gerald Christopher; (Cork, IE), Shanahan, Fergus; (Kinsale, IE) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030170217 Date filed: March 3, 2003 Abstract: A strain of Bifidobacterium isolated from resected and washed human gastrointestinal tract is significantly immunomodulatory following oral consumption in humans. The strain is useful in the prophylaxis and/or treatment of undesirable inflammatroy activity, especially gastrointestinal inflammatory activity such as inflammatory bowel disease or irritable bowel syndrome. The inflammatory activity may also be due to cancer. Excerpt(s): This invention relates to probiotic Bifidobacterium strains which have various applications in foodstuffs and in medicine. More particularly, the invention relates to probiotic strains of bifidobacteria which are capable of beneficially modifying and consequently alleviating observable symptoms in inflammatory disease. Consumers are becoming increasingly aware of matters which may be necessary for maintenance of their environment, health and nutrition. In response, scientific research has focussed upon the roles that diet, stress, and modern medical practices (e.g. antibiotics and radiotherapy) may play in threatening human health. In particular, population dynamics shifting towards older societies are increasing the incidence of illnesses which may be caused by deficient or compromised microflora such as gastrointestinal tract (GIT) infections, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)--Crohn's disease and ulcerative colitis, food allergies, antibiotic-induced diarrhoea, cardiovascular disease, and certain cancers (e.g. colorectal cancer). Probiotics have been defined as live microbial food supplements which beneficially affect the host by improving the intestinal microbial balance, or more broadly, as living microorganisms, which upon ingestion in certain numbers, exert health effects beyond inherent basic nutrition. Cocktails of various micro-organisms particularly species of Lactobacillus and Streptococcus, have traditionally been used in fermented dairy products to promote health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 155

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Co-administration of melanocortin receptor agonist and phosphodiesterase inhibitor for treatment of cyclic-AMP associated disorders Inventor(s): Carlson, Kenneth E.; (West Windsor, NJ), Macor, John E.; (Guilford, CT) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030069169 Date filed: March 4, 2002 Abstract: Co-administration of a melanocortin receptor agonist, particularly an MC-1R or MC-4R agonist, and a cAMP phosphodiesterase inhibitor is described for modulating levels of cyclic adenoise 3',5' monophosphate (cAMP) in a mammal. The inventive coadministration is useful in the treatment of diseases affected by activity of cAMP-PDE, including without limitation, inflammatory bowel disease, irritable bowel syndrome, rheumatoid arthritis, osteoarthritis, pancreatis, psoriasis, migraine, Alzheimer's Disease, Parkinson's disease, transplant rejection, asthma, acute respiratory distress syndrome, chronic obstructive pulmonary disease, stroke, and neurodegeneration of, and consequences of traumatic brain injury. Excerpt(s): This application claims the benefit of priority of U.S. applications Serial Nos. 60/273,206, and 60/273,291, filed Mar. 2, 2001, and U.S. Serial No. 60/289,719 filed May 9, 2001, the entire contents of which are incorporated herein by reference. The present invention relates to methods for treating diseases associated with intracellular levels of cAMP comprising co-administration of at least one compound that is a melanocortin receptor agonist and at least one compound that is a cAMP-PDE inhibitor, and to pharmaceutical compositions for practicing the claimed methods. Cyclic adenoise 3',5' monophosphate (cyclic AMP or cAMP) is a nucleotide messenger associated with inflammatory cell activity; it mediates the functional responses of cells to a multitide of hormones and neurotransmitters, including NF-.kappa.B. NF-.kappa.B is a pivotal component of the pro-inflammatory cascade, and its activation is a central event in initiating many inflammatory diseases. In a typical inflammatory response, NF-.kappa.B is activated in response to an inflammatory stimulus and once activated, induces expression of a wide array of pro-inflammatory genes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Compositions comprising sibutramine phosphodiesterase inhibitors

metabolites

in

combination

with

Inventor(s): Fang, Qun K.; (Wellesley, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20030096792 Date filed: October 23, 2002 Abstract: Methods are disclosed for the treatment and prevention of disorders and conditions such as, but are not limited to: eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse

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including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.Pharmaceutical compositions and dosage forms are also disclosed which comprise a racemic or optically pure sibutramine metabolite and an optional additional pharmacologically active compound. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/662,135, filed Sep. 14, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/372,158, filed Aug. 11, 1999, both of which are incorporated herein by reference in their entireties. The invention relates to methods of using and compositions comprising dopamine reuptake inhibitors such as racemic and optically pure metabolites of sibutramine, optionally in combination with other pharmacologically active compounds. Sibutramine, chemically named [N-1-[1-(4-chlorophenyl)cyclobutyl]3- -methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cyclic amino acids and derivatives thereof useful as pharmaceutical agents Inventor(s): Bryans, Justin Stephen; (Balsham, GB), Horwell, David Christopher; (Cambridge, GB), Thorpe, Andrew John; (Ann Arbor, MI), Wustrow, David Juergen; (Ann Arbor, MI), Yuen, Po-Wai; (Ann Arbor, MI) Correspondence: Warner-lambert Company; 2800 Plymouth RD; Ann Arbor; MI; 48105; US Patent Application Number: 20030220397 Date filed: May 30, 2003 Abstract: The invention is a novel series of cyclic amino acids which are useful in the treatment of epilepsy, faintness attacks, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, gastrointestinal disorders such as irritable bowel syndrome (IBS), and inflammation, especially arthritis. A pharmaceutical composition containing a compound of the invention as well as methods of preparing the compounds and novel intermediates useful in the preparation of the final compounds are included. Excerpt(s): This is a continuation of Ser. No. 09/485,382 filed Feb. 8, 2000, which is a 371 filing of PCT/US98/19876 filed Sep. 23, 1998, which claims priority to U.S. Provisional Serial No. 60/063,644 filed Oct. 27, 1997, and U.S. Provisional Serial No. 60/097,685 filed Aug. 24, 1998. wherein R.sub.1 is hydrogen or a lower alkyl radical and n is 4, 5, or 6 are known in U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. The uses disclosed are: protective effect against cramp induced by thiosemicarbazide; protective action against cardiazole cramp; the cerebral diseases, epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The patents are hereby incorporated by reference. wherein R to R.sup.14 are as defined below. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 157

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Early detection marker for chronic inflammatory associated diseases Inventor(s): Pereira, Heloise Anne; (Edmond, OK) Correspondence: Dunlap, Codding & Rogers P.C.; PO Box 16370; Oklahoma City; OK; 73114; US Patent Application Number: 20030170745 Date filed: March 7, 2003 Abstract: The present invention in one embodiment is an early detection marker for chronic inflammatory-associated diseases, including atherosclerosis, Alzheimer's disease, asthma, rheumatoid arthritis, osteoarthritis, and inflammatory diseases of the bowel such as Crohn's disease, Ulcerative colitis, Irritable bowel syndrome and Inflammatory bowel disease. The method, for example may comprise (1) obtaining a fluid sample from the subject, wherein the subject does not have an acute bacterial or viral infection when the fluid sample is obtained, (2) testing the fluid sample for a circulating or secreted CAP37 protein, and (3) concluding that the subject has a chronic inflammatory-associated disease when the CAP37 protein is detected in the fluid sample. The fluid sample may comprise serum, plasma, or cerebrospinal fluid, for example, or any other body fluid exposed to endothelial, vascular, or neuronal secretions. Excerpt(s): This application claims the benefit of U.S. Serial No. 60/363,114, filed Mar. 8, 2002, which is hereby expressly incorporated herein by reference in its entirety. The present invention relates to, but is not limited to, methods for detecting inflammatoryassociated diseases by detecting CAP37 proteins in a body fluid. Cationic Antimicrobial Protein of M.sub.r 37 kDa (CAP37) was originally isolated from granule extracts of human polymorphonuclear leukocytes (PMN) in 1984 (1). The amino acid sequence of PMN-CAP37 revealed its relation to members of the serine protease family that have a conserved catalytic active site consisting of his-57, asp-102 and ser-195 in the charge relay system (2). Of these sites, the conserved histidine and serine of the catalytic triad have been replaced with serine and glycine residues, respectively, rendering CAP37 ineffective as a serine protease (2,3). However, CAP37 has been demonstrated to have a diverse and exciting repertoire of functions. It was first analyzed regarding its bactericidal properties against Gram negative bacteria including, but not limited to, Salmonella typhimurium, Escherichia coli and Pseudomonas aeruginosa (4) and its ability to bind to and neutralize lipopolysaccharide (LPS)(5). Subsequently we showed CAP37 to be a potent chemoattractant for monocytes (6). Additionally, regarding its effects on the monocyte, CAP37 has been reported to stimulate their survival and thrombospondin secretion (7), also to enhance the LPS-stimulated release of prostaglandin E2 (8), interleukin 6 (IL-6)(9) and tumor necrosis factor-alpha (TNF.alpha.)(8-10). To add even further to its extensive range of known functions, CAP37 has been demonstrated to stimulate the reversible contraction of fibroblasts and endothelial cells (7) and to activate endothelial cell protein kinase C (PKC)(11). Recently, CAP37 released from stimulated PMN was reported to be taken up and sequestered in nearby endothelial mitochondria and has been suggested to protect against apoptosis (12). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Effects of glucagon-like peptide-1 (7-36) on antro-pyloro-duodenal motility Inventor(s): Goeke, Burkhard; (Gauting, DE), Schirra, Joerg; (Kirchhain, DE) Correspondence: Arnold & Porter; Attn: IP Docketing Department, Room 1126b; 555 Twelfth Street, NW; Washington; DC; 20004-1206; US Patent Application Number: 20030216292 Date filed: June 9, 2003 Abstract: The present invention provides an effective method for inhibiting antroduodenal motility in healthy subjects and patients suffering from various disorders, without the side effects associated with other pharmaceutical compositions. GLP-1 slows antro-duodenal motility and may be used for the treatment or prevention of gastrointestinal disorders such as diarrhea, postoperative dumping syndrome and irritable bowel syndrome, and also premedication in endoscopic procedures. Excerpt(s): The present invention relates to inhibiting antro-duodenal motility with GLP-1 and methods to alleviate discomfort during endoscopy and to alleviate symptoms of gastrointestinal disorders. Glucagon has been widely used to cause a variable reduction in gastroduodenal motility. The effect of glucagon appears to be dose-dependent with a minimally effective dose being 0.5 mg. Glucagon, however, does not facilitate colonoscopic evaluation (Norfleet, Gastrointest. Endosc., 24, 164-5, 1978), and at doses as high as 2 mg glucagon does not reduce contractions in the antrum (Gregerson et al., Scand. J. Gastroenterol. 23 (Supp 152), 42-47 (1988)). Furthermore, glucagon is contraindicated in persons with diabetes (Paul & Freyschmidt, ROFO Rortschr. Geb. Rontgenstr. Nuklearmed., 125, 31-7 (1996)), is expensive and its efficacy has been questioned. Side effects associated with the use of glucagon include nausea and vomiting. The effects are dose-dependent and can appear at a dose of 1 mg (Larsen et al., Scand. J. Gastroenterol. 21, 634-640, 1986; Gregersen et al., supra, Diamant Handbook Experimental Pharm, Lefevre ed., Vol. 66/2, 611-643, 1983). As dosages required to sufficiently reduce motility frequently exceed 1 mg, side effects from glucagon use are common. Such side effects render the patient extremely uncomfortable and often cause the endoscopic procedure to be interrupted or aborted. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Heterocyclic derivatives useful as pharmaceutical agents Inventor(s): Blakemore, David Clive; (Cambridge, GB), Bryans, Justin Stephen; (Balsham, GB), Williams, Sophie Caroline; (Cambridge, GB) Correspondence: David R. Kurlandsky; Warner-lambert Company Llc; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030203945 Date filed: May 5, 2003 Abstract: This invention relates to novel heterocyclic derivatives of the formula (VII), (VIII) or (IX) 1in which P, Q, R.sup.1-R.sup.6, m and n are as defined in the specification, and to pharmaceutically acceptable salts thereof. The compounds and pharmaceutical compositions containing them are useful in the treatment of a range of disorders including epilepsy, faintness attacks, hypokinesia, cranial disorders, depression, anxiety, panic, pain, neuropathological disorders, inflammatory diseases and gastrointestinal disorders, especially irritable bowel syndrome.

Patents 159

Excerpt(s): This invention relates to novel heterocyclic derivatives useful as pharmaceutical agents, to processes for their production, to pharmaceutical compositions containing them, and to their use for the treatment of the neurological conditions set out below. in which R.sub.1 is hydrogen or a lower alkyl radical and n is 4, 5, or 6. These compounds are described U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. Their disclosed uses are: the cerebral diseases, epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The disclosures of the above two patents are hereby incorporated by reference. in which R.sup.1 to R.sup.10 are each independently selected from straight or branched chain C.sup.1-C.sup.6 alkyl, substituted or unsubstituted benzyl or phenyl which substituents are selected from halogen, alkoxy, alkyl, hydroxy, carboxy, carboalkoxy, trifluoromethyl and nitro, any of R.sup.1 to R.sup.10 which is not one of the above being hydrogen. They are useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain and neuropathological disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Imidazo[1, 2-a] pyrazines for the treatment of irritable bowel syndrome Inventor(s): Bakthavatchalam, Rajagopal; (US), Gilligan, Paul J.; (US), Wilde, Richard G.; (US) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030220342 Date filed: May 1, 2003 Abstract: Provided herein are methods for treating a subject afflicted with irritable bowel syndrome comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition that comprises a pharmaceutically acceptable carrier and a compound of the formula 1wherein:X is CHR.sup.5, NR.sup.5, O, S, S(O).sub.n or a single bond, wherein n is equal to 0, 1 or 2;D is aryl or heteroaryl attached through an unsaturated carbon atom and wherein said aryl or heteroaryl is optionally substituted at any available position with from 1-5 of A.sup.1, A.sup.2, A.sup.3, A.sup.4 and A.sup.5; andR.sup.2 is C.sub.1-4 alkyl or C.sub.3-8 cycloalkyl, each of which is optionally substituted with from 1-3 hydroxy, halogen or C.sub.1-4 alkoxy, or wherein when X is a bond, R.sup.2 is CN, CF.sub.3, or C.sub.2F.sub.5. Excerpt(s): This application is a continuation of co-pending U.S. application Ser. No. 09/905,097, filed Jul. 13, 2001, now allowed, which in turn claims priority of provisional application Serial No. 60/218,339. These priority applications are hereby incorporated herein in their entireties. This invention relates to compounds which are novel imidazo[1,2-a]pyrazines, and to the use of such compounds as CRF receptor antagonists in the treatment of various neurological disorders. Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (POMC)-derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al., Rec. Prog. Horm.

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Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39 (1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors [J. E. Blalock, Physiological Reviews 69:1 (1989); J. E. Morley, Life Sci. 41:527 (1987)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Medicament containing cilansetron for the treatment of non-obstipative male irritable bowel syndrome patients Inventor(s): Biesheuvel, Egbertus Hendrikus Evert; (Weesp, NL), Caras, Steven David; (Marietta, GA), Cautreels, Werner L. M.; (Weesp, NL), Krause, Heinz Guenter; (Burgdorf, DE), Plekkenpol, Albertus Hermannus Dirk; (Hilversum, NL), Steinborn, Claus Rudolf; (Seelze, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030125349 Date filed: January 22, 2003 Abstract: The present invention relates to the use of cilansetron for the treatment of nonobstipative male IBS patients. Excerpt(s): This application claims priority of U.S. Provisional Patent Application No. 60/220,848, filed Jul. 26, 2000. Convention priority is also claimed based on Federal Republic of Germany Patent Application Nos. DE 100 36 645.7, filed Jul. 26, 2001 and DE 101 23 447.3, filed May 14, 2001. The present invention relates to a novel medicinal use of cilansetron or the acid addition salts thereof. Cilansetron is a 5HT.sub.3-receptor antagonist which falls within the scope of European Patent No. EP 297,651 B1 and has the chemical name (R)-(-)-4,5,6,8,9,10-hexahydro-10-[(2-methyl-1H-imidazol-1yl)methyl]-11H- -pyrido-[3,2,1-jk]-carbazol-11-one. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for distinguishing crohn's disease from ulcerative colitis and other gastrointestinal diseases by detecting the presence of fecal antibodies to saccharomyces cerevisiae Inventor(s): Boone, James Hunter; (Christiansburg, VA), Lyerly, David Maxwell; (Radford, VA), Wilkins, Tracy Dale; (Riner, VA) Correspondence: Shook, Hardy & Bacon Llp; 1200 Main Street; Kansas City; MO; 641052118; US Patent Application Number: 20030143649 Date filed: October 25, 2002 Excerpt(s): This application claims the benefit of priority to U.S. Provisional Application No. 60/335,812 filed on Oct. 26, 2001, the entirety of the disclosure of which is hereby incorporated by reference. Not Applicable. A method and apparatus for the differentiation of Crohn's disease from other gastrointestinal illnesses, such as ulcerative colitis and irritable bowel syndrome, using the presence of fecal anti-Saccharomyces cerevisiae antibodies (ASCA) as a marker for Crohn's disease are provided. The

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apparatus includes an enzyme-linked immunoassay or other immunoassay that utilizes antibodies specific to human immunoglobulins for the measurement of total endogenous ASCA in a human fecal sample. The method and apparatus may be used by healthcare providers to distinguish Crohn's disease from other gastrointestinal illnesses, such as ulcerative colitis and irritable bowel syndrome. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and composition for treatment of irritable bowel disease Inventor(s): Bergeron, Raymond J. JR.; (Gainesville, FL) Correspondence: Miles & Stockbridge; Suite 500; 1751 Pinnacle Drive; Mclean; VA; 22102-3833; US Patent Application Number: 20030153582 Date filed: August 1, 2002 Abstract: A method and composition for treating irritable bowel syndrome in a subject in need of such treatment, utilizing an amount of a polyamine having the formula:R-NH--(CH.sub.2).sub.a--NH--(CH.sub.2).sub.bH--(CH.sub.2).sub.c--NH.sub.2, 1)CF.sub.3--C.sub.6H.sub.5--(CH.sub.2).sub.a--NH--(CH.sub.2).sub.b--NH--(CH.sub.2).sub.c--NH--(CH.sub.2).sub.d--NH--(CH.sub.2).sub.e--C.sub.6H.sub.5--- CF.sub.3, 2)R--NH--(CH.sub.2).sub.a--NH--C.sub.6H.sub.6--NH--(CH.sub.2).sub.b--NH--R and 3)PIP--(CH.sub.2).sub.aNH--(CH.sub.2).sub.b--NH--(CH.sub.2).sub.c--PIP, 4)wherein:R is alkyl, aryl, aralkyl, alkaryl, or cyclo-alkyl having up to about 10 carbon atoms, and any of the alkyl chains may optionally be interrupted by at least one etheric oxygen atom,PIP is piperidine anda, b, c, d, and e may be the same or different and are integers from 1-10 effective to treat irritable bowel syndrome. Excerpt(s): The present invention relates to pharmaceutical compositions and methods for the treatment of irritable bowel disease (IBD) [also termed: irritable bowel syndrome (IBS)]; more particularly for the treatment of diarrhea-predominant IBD. Irritable bowel syndrome (IBS), a chronic or recurring gastrointestinal disorder, afflicts as many as 24% of women and 19% of men in the U.S., Europe, Japan, and China. IBS produces abdominal pain or discomfort in its victims and accounts for about one-eighth of primary care and more than one-fourth of gastroenterology practice. IBS has tremendous societal and economic impact since persons with IBS symptoms miss three times as many work days as those without and incur 70% higher health care costs. The American Gastroenterological Association has recently underscored the importance of IBS by issuing both a position statement (American Gastroenterological Association (AGA) Medical Position Statement: Irritable Bowel Syndrome. Gastroenterology 112:2118-2119 (1997)) and a technical review (Drossman D A, Whitehead W E, Camilleri M., "Irritable bowel syndrome: a technical review for practice guideline development", Gastroenterology 112:2120-2137 (1997)) on IBS. The description herein of IBS is based chiefly on these documents and on other current literature (such as that reviewed in Snape W J Jr., "Irritable bowel syndrome", In: Bockus Gastroenterology, 5th edition (W. S. Haubrich, F. Schoffner, ed.) Philadelphia: W. B. Saunders, pp. 1619-1636 (1995)). IBS presents itself as abdominal pain accompanied by altered bowel habits. There is no established biological marker for IBS, which appears to result from faulty regulation in both the gastrointestinal and nervous systems. Once clinicians rule out other possible causes of IBS symptoms, they must devise a treatment plan based upon the severity and nature of the symptoms as well as other factors such as the degree of impairment the individual is experiencing in the activities of daily living. At present, treatment options

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range from education and dietary modification to drug therapy to psychological therapy. Drug and/or psychological therapy is called for in those 30% of IBS patients with moderate or severe symptoms. Given an IBS prevalence of 19% to 24%, IBS sufferers requiring such therapy represent 6-7% of the population at large, or well over 100 million individuals in continual need of such therapy in the U.S., Europe, Japan, and China. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the stereoselective synthesis of cyclic amino acids Inventor(s): Blakemore, David Clive; (Cambridge, GB), Bryans, Justin Stephen; (Balsham, GB), Williams, Sophie Caroline; (Cambridge, GB) Correspondence: Elizabeth M Anderson; Warner Lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030069438 Date filed: June 6, 2002 Abstract: 1The instant invention is a route to stereospecific 3-substituted 5-membered ring isomers of Formula (A). The final products are useful as agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammation especially arthritis, sleep disorders, premenstrual syndrome, and hot flashes. The invention provides novel routes to synthesize stereoselectively analogs of gabapentin (Neurontin.TM.) of Formulas (I), (II), (III) and (IV) wherein R is C.sub.1-C.sub.10 alkyl or C.sub.3-C.sub.10 cycloalkyl and pharmaceutically acceptable salts thereof. Excerpt(s): wherein R.sub.1 is hydrogen or a lower alkyl radical and n is 4, 5, or 6 are known in U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. The uses disclosed are: protective effect against cramp induced by thiosemicarbazide; protective action against cardiazole cramp; the cerebral diseases, epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The patents are hereby incorporated by reference. or a pharmaceutically acceptable salt thereof wherein R is hydrogen or a lower alkyl; and R.sub.1 to R.sub.8 are each independently selected from hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms, phenyl, benzyl, fluorine, chlorine, bromine, hydroxy,. hydroxymethyl, amino, aminomethyl, trifluoromethyl, -CO.sub.2H, --CO.sub.2R.sub.15, --CH.sub.2CO.sub.2H, --CH.sub.2CO.sub.2R.sub.15, -OR.sub.15 wherein R.sub.15 is a straight or branched alkyl of from 1 to 6 carbons, phenyl, or benzyl, and R.sub.1 to R.sub.8 are not simultaneously hydrogen. This patent application is hereby incorporated by reference. when R.sub.3, R.sub.5, Z.sub.1, Z.sub.2, or Z.sub.3 is X(CH.sub.2).sub.nR.sub.8 and n is not zero, X is oxygen or NR.sub.6 when R.sub.8 is OR.sub.6 or CO.sub.2H. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for treating apnea, apnea disorders, and other disorders using optically pure (-) norcisapride Inventor(s): Barberich, Timothy J.; (Concord, MA), Rubin, Paul D.; (Sudbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20030158229 Date filed: February 26, 2003 Abstract: Methods for the prevention, treatment, or management of apnea, apnea disorders, bulimia nervosa, irritable bowel syndrome, urinary incontinence, bradycardia, bradyarrhythmia, syncope, other disorders, or symptoms thereof using (-) norcisapride, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer. Excerpt(s): The invention relates to methods of prevention, treatment, or management, of apnea, apnea disorders, bulimia, other disorders, or symptoms thereof. Apnea is defined in Stedman's Medical Dictionary, 26.sup.th Edition, Williams and Wilkins (1995), as the absence of breathing. There are a number of disorders associated with apnea, which are characterized by interrupted breathing in which a person stops breathing long enough to decrease the amount of oxygen and increase the amount of carbon dioxide in the blood and brain Each type of apnea involves the absence of airflow at the nose or the mouth, typically for at least 10 seconds. Various apnea disorders exist, including: central apnea, which results from medullary depression and inhibits respiratory movement; deglutition apnea, which is the inhibition of breathing during swallowing; obstructive or peripheral apnea, which is either a result of obstruction of air passages or inadequate respiratory muscle activity; sleep apnea, which is central and/or obstructive apnea during sleep; and sleep induced apnea, which results from failure of the respiratory center to stimulate adequate respiration during sleep. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for treating irritable bowel syndrome Inventor(s): Mangel, Allen Wayne; (Chapel Hill, NC), Northcutt, Allison Ruth; (Raleigh, NC) Correspondence: David J Levy, Corporate Intellectual Property; Glaxosmithkline; Five Moore DR., PO Box 13398; Research Triangle Park; NC; 27709-3398; US Patent Application Number: 20030036549 Date filed: June 10, 2002 Abstract: This invention relates to the use of 5-HT3 receptor antagonists in the treatment of nonconstipated female IBS patients. Excerpt(s): The invention relates to a new medical use for compounds which act as antagonists of 5-hydroxytryptamine (5-HT) at 5-HT.sub.3 receptors. 5-HT.sub.3 receptor antagonists may be identified by methods well known in the art, for example by their ability to inhibit 3-(5-methyl-1H-imidazole4-yl)-1-[1-[.sup.3H]-methyl-1H-indol-3-yl]-1prop- anone binding in rat entorhinal cortex homogenates (following the general procedure described by G Kilpatrick et al, Nature, 1987, 330, 746-748), and/or by their effect on the 5-HT-induced Bezold-Jarisch (B-J) reflex in the cat (following the general

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method described by A Butler et al, Br. J. Pharmacol., 94, 397412 (1988)). A number of different 5-HT.sub.3 receptor antagonists have been disclosed, for example those of group A: indisetron, Ro-93777, YM-114, granisetron, talipexole, azasetron, tropisetron, mirtazapine, ramosetron, ondansetron, lerisetron, alosetron, N-3389, zacopride, cilansetron, E-3620, lintopride, KAE-393, itasetron, mosapride and dolasetron. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of diagnosing irritable bowel syndrome and other disorders caused by small intestinal bacterial overgrowth Inventor(s): Lin, Henry C.; (Manhattan Beach, CA), Pimentel, Mark; (Los Angeles, CA) Correspondence: Sidley Austin Brown & Wood Llp; 555 West Fifth Street; Los Angeles; CA; 90013-1010; US Patent Application Number: 20030031625 Date filed: March 26, 2002 Abstract: Disclosed is a method of diagnosing irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, attention deficit/hyperactivity disorder, autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus, or Crohn's disease, which involves detecting the presence of small intestinal bacterial overgrowth (SIBO) in a human subject having at least one symptom associated with a suspected diagnosis of any of those diagnostic categories. Also disclosed is a method of treating these disorders, and other disorders caused by SIBO, that involves at least partially eradicating a SIBO condition in the human subject. The method includes administration of anti-microbial or probiotic agents, or normalizing intestinal motility by employing a prokinetic agent. The method improves symptoms, including hyperalgesia related to SIBO and disorders caused by SIBO. Also disclosed is a kit for the diagnosis or treatment of irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, attention deficit/hyperactivity disorder, autoimmune diseases, or Crohn's disease. Excerpt(s): This application is a division of Ser. No. 09/374,142, which was filed Aug. 11, 1999. Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. This invention relates to the medical arts. It relates to a method of diagnosing and treating irritable bowel syndrome and other disorders, such as Crohn's disease, chronic fatigue syndrome, fibromyalgia, depression, attention deficit/hyperactivity disorder, multiple sclerosis, systemic lupus erythematosus and other autoimmune diseases in a human subject. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use Inventor(s): De Tejada, Inigo Saenz; (Madrid, ES), Earl, Richard A.; (Westford, MA), Garvey, David S.; (Dover, MA), Khanapure, Subhash P.; (Clinton, MA) Correspondence: Edward D Grieff; Hale & Dorr Llp; 1455 Pennsylvania Ave, NW; Washington; DC; 20004; US Patent Application Number: 20030023087 Date filed: August 13, 2002 Abstract: The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3',5'-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e.g., irritable bowel syndrome (IBS). Excerpt(s): This is a continuation-in-part of U.S. application Ser. No. 09/145,142, filed Sep. 1, 1998, allowed, which is a continuation-in-part of U.S. application Ser. No. 08/740,764, filed Nov. 1, 1996, issued as U.S. Pat. No. 5,874,437; and is a continuation-inpart of PCT/US97/19870, filed Oct. 31, 1997, which claims priority to U.S. application Ser. No. 08/740,764, filed Nov. 1, 1996, issued as U.S. Pat. No. 5,874,437. The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions comprising at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one phosphodiesterase inhibitor, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of

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cyclic guanosine 3',5'-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, and glucoma, and diseases characterized by disorders of gut motility, such as irritable bowel syndrome (IBS). Adequate sexual function is a complex interaction of hormonal events and psychosocial relationships. There are four stages to sexual response as described in the International Journal of Gynecology & Obstetrics, 51(3):265-277 (1995). The first stage of sexual response is desire. The second stage of sexual response is arousal. Both physical and emotional stimulation may lead to breast and genital vasodilation and clitoral engorgement (vasocongestion). In the female, dilation and engorgement of the blood vessels in the labia and tissue surrounding the vagina produce the "orgasmic platform," an area at the distal third of the vagina where blood becomes sequestered. Localized perivaginal swelling and vaginal lubrication make up the changes in this stage of sexual response. Subsequently, ballooning of the proximal portion of the vagina and elevation of the uterus occurs. In the male, vasodilation of the cavernosal arteries and closure of the venous channels that drain the penis produce an erection. The third stage of sexual response is orgasm, while the fourth stage is resolution. Interruption or absence of any of the stages of the sexual response cycle can result in sexual dysfunction. One study found that 35% of males and 42% of females reported some form of sexual dysfunction. Read et al, J. Public Health Med., 19(4):387-391 (1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel 5-HT3 receptor antagonists and methods of use Inventor(s): Becker, Cyrus; (Menlo Park, CA), Druzgala, Pascal; (Santa Rosa, CA), Pfister, Jurg R.; (Los Altos, CA), Zhang, Xiaming; (Campbell, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030158221 Date filed: January 21, 2003 Abstract: The subject invention provides useful and novel 5-HT3 antagonists. The subject invention also provides methods for synthesizing the compounds of invention. The invention also provides methods for the treatment of irritable bowel syndrome and other such conditions. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/350,504, filed Jan. 18, 2002. Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorder thought to result from dysregulation of intestinal motor, sensory and CNS function. In the United States, the estimated prevalence is 15% to 20%, and 75% of patients are women. Despite its prevalence, IBS is poorly understood. It is one of over 20 functional gastrointestinal (GI) disorders that are not explained by identifiable structural or biochemical abnormalities. IBS is characterized by persistent or recurrent symptoms of abdominal pain with diarrhea and/or constipation. IBS is believed to relate to abnormalities in motility and/or afferent sensitivity as

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mediated by the central nervous system. Patients with IBS have a diminished quality of life and use significant health care resources. Treatment for patients diagnosed with IBS has included antidepressant drugs, tranquilizers and laxatives. Pharmacological intervention in diarrhea-predominant IBS focuses on the reduction of bowel motility, spasms and transit times. Peripherally acting opiod ligands such as the petidine congeners diphenoxylate and loperamide and the k-opiod agonist fedotozine slow gastrointestinal transit by their effects on the circular and longitudinal muscle. While these drugs show some effects on intestinal motility, their effects on IBS-related abdominal pain and intestinal relief is generally insufficient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel thiocarbamic acid derivatives and the pharmaceutical compositions containing the same Inventor(s): Yi, Jung Bum; (Kyunggi-do, KR), Kim, Hee Doo; (Seoul, KR), Lee, Jee Woo; (Seoul, KR), Oh, Uh Taek; (Kyunggi-do, KR), Park, Hyeung Geun; (Seoul, KR), Park, Young Ho; (Seoul, KR), Suh, Young Ger; (Kyunggi-do, KR) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030203944 Date filed: February 3, 2003 Abstract: The present invention relates to an antagonist against vanilloid receptor and the pharmaceutical compositions containing the same. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, postoperative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fevescence, stomachduodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases. Excerpt(s): The present invention relates to thiocarbamic acid derivatives and the pharmaceutical compositions containing the same, and particularly, to novel thiocarbamic acid derivatives as an antagonist against vanilloid receptor (VR) and the pharmaceutical compositions thereof. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomachduodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides pharmaceutical compositions for prevention or treatment of these diseases. Yet, the diseases described above are only for enumeration, not to limit the scope of clinical application of vanilloid receptor antagonist. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel thiourea derivatives and the pharmaceutical compositions containing the same Inventor(s): Choi, Jin Kyu; (Kyunggi-do, KR), Jeong, Yeon Su; (Kyunggi-do, KR), Joo, Yung Hyup; (Seoul, KR), Kim, Hee Doo; (Seoul, KR), Kim, Jin Kwan; (Seoul, KR), Kim, Sun Young; (Kyunggi-do, KR), Koh, Hyun Ju; (Seoul, KR), Lee, Jee Woo; (Seoul, KR), Lee, Yong Sil; (Seoul, KR), Lim, Kyung Min; (Kyunggi-do, KR), Moh, Joo Hyun; (Kyunggi-do, KR), Oh, Uh Taek; (Kyunggi-do, KR), Oh, Young Im; (Kyunggi-do, KR), Park, Hyeung Geun; (Seoul, KR), Park, Ok Hui; (Chungchongnam-do, KR), Park, Young Ho; (Seoul, KR), Suh, Young Ger; (Kyunggi-do, KR), Yi, Jung Bum; (Kyunggi-do, KR) Correspondence: Finnegan Henderson; Farabow Garrett & Dunner; 1300 I Street N W; Washington; DC; 20005-3315; US Patent Application Number: 20030153596 Date filed: July 9, 2002 Abstract: The present invention relates to novel thiourca derivatives as a modulator for vanilloid receptor (VR) and the phar- maceutical compositions containing the same. As diseases associated with the activity of vanilloid receptor, pain acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflam- matory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases. Excerpt(s): The present invention relates to novel thiourea derivatives and the pharmaceutical compositions containing the same, and particularly, to novel thiourea compounds as a modulator for vanilloid receptor (VR) and the pharmaceutical compositions thereof. Here, the modulator means the thing that can be bonded to the receptor to act as an antagonist or an agonist. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arttralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulnonary disease, irritation of skin, eye or mucous membrane, fervescence, stomachduodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides pharmaceutical compositions for prevention or treatment of these diseases. Yet, the diseases described above are only for enumeration, not to limit the scope of clinical application of vanilloid receptor modulator. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a main pungent component in hot peppers. Hot peppers have been used, for a long time, not only as a spice but also as traditional medicine in the treatment of gastric disorders and when applied locally, for the relief of pain and inflammation (Szallasi and Blumberg, 1999, Pharm, Rev. 51, ppl59-211). Capsaicin has a wide spectrum of biological actions, and not only exhibits effects on the cardiovascular and respiratory systems but also induces pain and irritancy on local application. Capsaicin, however, after such induction of pain, induces desensitization, both to capsaicin itself and also to other noxious stimuli to make the pain stopped. Based on this property, capsaicin and its analogues such as olvanil, nuvanil, DA-5018, SDZ-249482, resiniferatoxin are either used as analgesic agent, therapeutic agent for incontinentia urinae or skin disorder, or under development (riggleworth and Walpole, 1998, Drugs of the Future 23, pp 531-538).

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

Oxo or oxy-pyridine compounds as 5-HT4 receptor modulators Inventor(s): Gymer, Geoffrey; (Sandwich, GB), Kawamura, Kiyoshi; (Aichi-ken, JP), Mihara, Sachiko; (Aichi-ken, JP), Morita, Mikio; (Aichi-ken, JP), Nukui, Seiji; (Aichi-ken, JP), Stobie, Alan; (Sandwich, GB), Uchida, Chikara; (Aichi-ken, JP) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030207875 Date filed: January 7, 2003 Abstract: This invention provides compounds of the formula (I) and (II): 1or the pharmaceutically acceptable esters thereof, and the pharmaceutically acceptable salts thereof: wherein R.sup.1 is hydrogen or halo; R.sup.2 and R.sup.3 are independently hydrogen or C.sub.1-6 alkyl; R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-6 alkyl; R.sup.6 is hydrogen, C.sub.1-12 alkyl, C.sub.1-6 alkoxy (C.sub.1-6)alkyl or C.sub.1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of C.sub.3-8 cycloalkyl, aryl, heteroaryl and heterocyclic; R.sup.7 and R.sup.8 are hydrogen or taken together may form alkylene chain having one or two carbon atoms; R.sup.9 is C.sub.1-6 alkyl or C.sub.3-8 cycloalkyl; R.sup.10 is C.sub.1-6 alkyl or NR.sup.11R.sup.12; L is (CR.sup.11R.sup.12).sub.n or NR.sup.11; M is NR.sup.11 or (CR.sup.11R.sup.12).sub.n; R.sup.11 and R.sup.12 are independently hydrogen or C.sub.1-6 alkyl; n is an integer from 0 to 5; and m is an integer from 0 to 2; said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo and C.sub.1-6 alkyl; with the proviso that when R.sup.9 is C.sub.1-6 alkyl, L is not NR.sup.11.These compounds have 5-HT.sub.4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound. Excerpt(s): This invention relates to novel oxo or oxy-pyridine compounds. These compounds have 5-HT.sub.4 receptor binding activity (e.g., agonist or antagonist activities), and thus are useful for the treatment of or prevention of gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, irritable bowel syndrome, constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, alzheimers disease, cognitive disorder, emesis, migraine, neurological disease, pain, ischaemic stroke, anxiety, cardiovascular disorder or the like, in mammalian, especially human. The present invention also relates to a pharmaceutical composition comprising the above compounds. Serotonin (5-HT) receptors are known to have a plurality of subtypes such as 5-HT.sub.1, 5-HT.sub.2, 5HT.sub.3 and 5-HT.sub.4. These 5-HT.sub.4 receptors are disclosed in, for example, European Journal of Pharmacology 146 (1988), 187-188, and Naunyn-Schmiedeberg's Arch. Pharmacol. (1989) 340:403-410. 5-HT.sub.4 receptor modulators (e.g., agonists and antagonists) are found to be useful for the treatment of a variety of diseases such as gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, nonulcer dyspepsia, irritable bowel syndrome, constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, alzheimers disease, cognitive disorder, emesis, migraine, neurological disease, pain, and cardiovascular disorders such as cardiac failure and heart arryhthmia (See TiPs, 1992, 13, 141; Ford A.

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P. D. W. et al., Med. Res. Rev., 1993, 13, 633; Gullikson G. W. et al., Drug Dev. Res., 1992, 26, 405; Richard M. Eglen et al, TiPS, 1995, 16, 391; Bockaert J. Et al., CNS Drugs, 1, 6; Romanelli M. N. et al., Arzheim Forsch./Drug Res., 1993, 43, 913; Kaumann A. et al., Naunyn-Schmiedeberg's. 1991, 344, 150; and Romanelli M. N. et al., Arzheim Forsch./Drug Res., 1993, 43, 913). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical composition and method of modulating cholinergic function in a mammal Inventor(s): Coe, Jotham W.; (Niantic, CT), Sands, Steven B.; (Stonington, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030008892 Date filed: March 25, 2002 Abstract: A pharmaceutical composition and method of modulating cholinergic function in a mammal comprising administration of a NRPA compound or a pharmaceutically acceptable salt thereof; and an anti-emetic/anti-nausea agent or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. The NRPA compound and the anti-emetic/anti-nausea agent are present in amounts that render the composition effective modulating cholinergic function or in the treatment of a diorder or condition selected from inflammatory bowel disease (including but not limited to ulcerative colitis, pyoderma gangrenosum and Crohn's disease), irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy, chemical dependencies and addictions (e.g., dependencies on, or addictions to nicotine (and/or tobacco products), alcohol, benzodiazepines, barbiturates, opioids or cocaine), headache, migraine, stroke, traumatic brain injury (TBI), obsessive-compulsive disorder (OCD), psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multiinfarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Tourette's Syndrome. The method of using these compositions is also disclosed. Excerpt(s): The present invention relates to pharmaceutical compositions for modulating cholinergic function in a mammal comprising a nicotinic receptor partial agonist compound in combination with an anti-emetic/anti-nausea agent and a pharmaceutically acceptable carrier. The nicotinic receptor partial agonists (NRPAs) included herein are aryl fused azapolycyclic compounds. NRPAs are not limited to those described here. The term NRPA refers to all chemical compounds which bind at neuronal nicotinic acetylcholine specific receptor sites in mammalian tissue and elicit a partial agonist response. A partial agonist response is defined here to mean a partial, or incomplete functional effect in a given functional assay. Additionally, a partial agonist will also exhibit some degree of antagonist activity by its ability to block the action of a full agonist (Feldman, R. S., Meyer, J. S. & Quenzer, L. F. Principles of Neuropsychopharmacology, 1997; Sinauer Assoc. Inc.). The present invention may be used to treat mammals (e.g. humans) for inflammatory bowel disease (including but not

Patents 171

limited to ulcerative colitis, pyoderma gangrenosum and Crohn's disease), irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy, chemical dependencies and addictions (e.g., dependencies on, or addictions to nicotine (and/or tobacco products), alcohol, benzodiazepines, barbiturates, opioids or cocaine), headache, migraine, stroke, traumatic brain injury (TBI), obsessive-compulsive disorder (OCD), psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multiinfarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Tourette's Syndrome with a decrease in the incidence and severity of unwanted side effects such as nausea and/or stomach upset. The present invention also relates to the combination use of NRPAs and anti-emetic/anti-nausea agents resulting in modulation of cholinergic function without nausea. The combination will provide an improved treatment paradigm than NRPAs alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Predicting patient responsiveness to serotonergic therapy Inventor(s): Camilleri, Michael L.; (Rochester, MN), Urrutia, Raul A.; (Rochester, MN) Correspondence: Fish & Richardson P.C.; 3300 Dain Rauscher Plaza; 60 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20030143548 Date filed: January 28, 2002 Abstract: Methods to predict a patient's responsiveness to 5-HT.sub.3 receptor antagonists are disclosed. The methods allow a clinician to predict a patient's responsiveness to 5-HT.sub.3 receptor antagonists by determining the correlation that exists between a genotype in the promoter region of the gene encoding a serotonin transporter protein and patient response to 5-HT.sub.3 receptor antagonist therapy. In addition, methods to treat patients suffering from diarrhea-predominant irritable bowel syndrome and methods to identify a patient population for inclusion in a 5-HT.sub.3 receptor antagonist clinical trial are disclosed. Excerpt(s): Funding for the work described herein was provided in part by the Federal Government, which may have certain rights in the invention. This invention relates to serotonergic therapy, and more particularly to predicting a patient's responsiveness to serotonergic receptor antagonists. Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in western populations, with an adult prevalence of approximately 15%. The cardinal features of IBS are recurrent abdominal pain and altered bowel habits. Diarrhea-predominant IBS has been associated with accelerated small bowel and/or colonic transit and with rectal hypersensitivity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Probiotic lactobacillus casei strains Inventor(s): Collins, John Kevin; (Doughcloyne, IE), Kiely, Barry; (Passage West, IE), O'Mahony, Liam; (Cork, IE), O'sullivan, Gerald Christopher; (Cork, IE), Shanahan, Fergus; (Kinsale, IE) Correspondence: Jacobson Holman; Professional Limited Liability Company; 400 Seventh STREET. N.W.; Washington; DC; 20004; US Patent Application Number: 20030113306 Date filed: July 25, 2002 Abstract: A Lactobacillus casei strain or a mutant or variant thereof isolated from resected and washed human gastrointestinal tract is significantly immunomodulatory following oral consumption in humans. In particular a Lactobacillus casei strain, AH101, AH104, AH111, AH112 or AH113 or mutants or variants are thereof are useful in the prophylaxis and/or treatment of inflammatory activity especially undesirable gastrointestinal inflammatory activity, such as inflammatory bowel disease or irritable bowel syndrome. Excerpt(s): The invention relates to Lactobacillus casei strains and their use as probiotic bacteria in particular as immunomodulatory biotherapeutic agents. The defense mechanisms to protect the human gastrointestinal tract from colonization by intestinal bacteria are highly complex and involve both immunological and non-immunological aspects (1). Innate defense mechanisms include the low pH of the stomach, bile salts, peristalsis, mucin layers and anti-microbial compounds such as lysozyme (2). Immunological mechanisms include specialized lymphoid aggregates, underlying M cells, called peyers patches which are distributed throughout the small intestine and colon (3). Luminal antigens presented at these sites result in stimulation of appropriate T and B cell subsets with establishment of cytokine networks and secretion of antibodies into the gastrointestinal tract (4). In addition, antigen presentation may occur via epithelial cells to intraepithelial lymphocytes and to the underlying lamina propria immune cells (5). Therefore, the host invests substantially in immunological defense of the gastrointestinal tract. However, as the gastrointestinal mucosa is the largest surface at which the host interacts with the external environment, specific control mechanisms must be in place to regulate immune responsiveness to the 100 tons of food which is handled by the gastrointestinal tract over an average lifetime. Furthermore, the gut is colonized by over 500 species of bacteria numbering 10.sup.11-10.sup.12/g in the colon. Thus, these control mechanisms must be capable of distinguishing non-pathogenic adherent bacteria from invasive pathogens, which would cause significant damage to the host. In fact, the intestinal flora contributes to defense of the host by competing with newly ingested potentially pathogenic micro-organisms. Bacteria present in the human gastrointestinal tract can promote inflammation. Aberrant immune responses to the indigenous microflora have been implicated in certain disease states, such as inflammatory bowel disease. Antigens associated with the normal flora usually lead to immunological tolerance and failure to achieve this tolerance is a major mechanism of mucosal inflammation (6). Evidence for this breakdown in tolerance includes an increase in antibody levels directed against the gut flora in patients with IBD. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Proceture to use staphylococcal bacteria Inventor(s): Gottfries, Carl-Gerhard; (Goteborg, SE), Regland, Bjorn; (Molndal, SE) Correspondence: Drum & Roth; 53 West Jackson Boulevard; Chicago; IL; 60604-3606; US Patent Application Number: 20020192238 Date filed: June 20, 2002 Abstract: The Invention relates to a procedure for the use of staphylococcal bacteria or a product derived therefrom. The aforementioned staphylococcal bacteria or a product derived therefrom are intended for the production of a pharmaceutical preparation for the treatment of and/or for the prevention of irritable bowel syndrome. Excerpt(s): The present invention relates to a procedure for the use of staphylococcal bacteria or a product derived therefrom. Irritable Bowel Syndrome (IBS) is a bowel disease with variable symptoms, which may be referred to in Swedish as the equivalent of "irritable large intestine". There are no biological markers for the disease. Two systems of classification based on the symptoms have been drawn up to define the disease. One is known as the "Manning criteria" and the other as the "Rome criteria". In Manning, A. P., Thompson, W. G., Heaton, K. W., Morris, A. F. (1978), "Towards Positive Diagnosis of the Irritable Bowel", Br. Med. J., 2:653-654, four symptoms are identified which, in a significant fashion, distinguish patients with IBS from patients with some other known organic disease; these are tension and swelling in the abdomen, pain alleviation in conjunction with bowel activity, more frequent bowel motions in conjunction with abdominal pains and looser bowel motions in conjunction with abdominal pains. In addition to these, it was also stated that two symptoms are also often encountered, namely mucous-like motions and a sense of incomplete evacuation of the bowel. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stable hydrate of a muscarinic receptor antagonist Inventor(s): Dunn, Peter James; (Sandwich, GB), Matthews, John George; (Sandwich, GB), Newbury, Trevor Jack; (Sandwich, GB), O'Connor, Garry; (Sandwich, GB) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030191176 Date filed: March 25, 2003 Abstract: A stable solid hydrate of a muscarinic receptor antagonist is useful in the treatment of irritable bowel syndrome, diverticular disease, oesophageal achalasia, chronic obstructive airways disease, over active bladder (including symptoms of incontinence, urge and frequency), urinary incontinence, neurogenic urinary urgency or pollakiuria, treatment of bladder functional disorder, urinary leakage, painful or difficult urination caused by neurogenic bladder, spastic or hypertonic bladder, dysfunctional bladder syndrome, gastrointestinal disorders including gastrointestinal hyperactivity, and relaxing effect on intestinal smooth muscle cells. Excerpt(s): In addition, the invention relates to pharmaceutical compositions containing the hydrate of the invention and to uses of said hydrate in medicine. Such pharmaceutical compositions are particularly relevant to the treatment of conditions for which an antagonist of muscarinic receptors is required, such as irritable bowel

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syndrome, diverticular disease, oesophageal achalasia, chronic obstructive airways disease, over active bladder including symptoms of incontinence, urge and frequency, urinary incontinence, neurogenic urinary urgency or pollakiuria, treatment of bladder functional disorder, urinary leakage, painful or difficult urination caused by neurogenic bladder, spastic or hypertonic bladder, dysfunctional bladder syndrome, gastrointestinal disorders including gastrointestinal hyperactivity, and relaxing effect on intestinal smooth muscle cells. European patent 0388054 describes a family of 3substituted pyrrolidine derivatives including darifenacin and pharmaceutically acceptable salts thereof as muscarinic receptor antagonists. The pharmaceutically acceptable salts include acid addition salts, specifically the hydrochloride, hydrobromide, hydrofluoride, sulphate or bisulphate, phosphate or hydrogen phosphate, acetate, besylate, citrate, fumarate, gluconate, lactate, maleate, mesylate, succinate and tartrate salts. The hydrobromide salt of darifenacin has been the preferred compound for medical usage. The salt is produced from the corresponding anhydrous free base. However, a problem associated with the free base is that it is very unstable, having a shelf life of only one month. Additionally it can be difficult to produce the free base in a sufficiently pure form for pharmaceutical use. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Substituted homopiperidinyl benzimidazole analogues as fundic relaxants Inventor(s): Guillemont, Jerome Emile Georges; (Issy-les-Moulineaux, FR), Janssens, Frans Eduard; (Beerse, BE), Sommen, Francois Maria; (Beerse, BE) Correspondence: Philip S Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20030139393 Date filed: June 19, 2002 Abstract: The present invention relates to compounds of formula (I) 1their prodrugs, Noxides, addition salts, quaternary amines and stereochemically isomeric forms, wherein the bivalent radical --{circle over (A)}-- represents a saturated or an unsaturated homopiperidinyl having one double bond, and wherein said bivalent radical --{circle over (A)}-- is substituted with R.sup.2 being hydrogen, hydroxy, C.sub.1-4alkyl, or C.sub.1-4alkyloxy; -a.sup.1=a.sup.2-a.sup.3=a.sup.4represents an optionally substituted bivalent radical; R.sup.1 is hydrogen, C.sub.1-6alkyl, aryl.sup.1, C.sub.16alkyl substituted with aryl.sup.1, C.sub.1-4alkyloxycarbonyl, aryl.sup.1carbonyl, aryl.sup.1C.sub.1-6alkylarbonyl C.sub.1-4alkylcarbonyl, trifluoromethyl, trifluoromethylcarbonyl, C.sub.1-6alkylsulfonyl, aryl.sup.1sulfonyl, methanesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, dimethylsulfamoyl; X represents O, S or NR.sup.3, wherein R.sup.3 is hydrogen, C.sub.1-6alkyl, methanesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, dimethylsulfamoyl, C.sub.1-4alkyl substituted with aryl.sup.2 and optionally with hydroxy, C.sub.1-4alkylcarbonylC.sub.1-4alkyl substituted with aryl.sup.2; aryl.sup.1 is optionally substituted phenyl, optionally substituted pyridinyl, naphthyl, quinolinyl, or 1,3-benzodioxolyl; aryl.sup.2 is optionally substituted phenyl; fundic relaxating activity. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating dyspeptic symptoms, irritable bowel syndrome and other conditions related to a hampered or impaired relaxation of the fundus. Excerpt(s): The present invention is concerned with novel compounds of formula (I) having fundic relaxating activity. The invention further relates to methods for preparing

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such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicine of said compounds. EP-A-0,079,545 discloses piperazinyl substituted benzimidazole derivatives with antihistaminic acitivity. Unexpectedly, it was found that the present novel compounds of formula (I) have fundic relaxating properties and are therefore useful to alleviate symptoms resulting from an impaired relaxation of the fundus to food ingestion. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Thiophenyl triazol-3-one derivatives as smooth muscle relaxants Inventor(s): Hewawasam, Piyasena; (Middletown, CT), King, Dalton; (Hamden, CT), Lodge, Nicholas J.; (Madison, CT), Starrett, John E.; (Middletown, CT), Sun, Li-Quang; (Glastonbury, CT) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030144333 Date filed: October 8, 2002 Abstract: The present invention provides novel [1,2,4]triazole-3-one derivatives having the general formula (I) 1wherein:Q is 2and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are as defined herein or a nontoxic pharmaceutically acceptable salt or solvate thereof which are smooth muscle relaxants and useful in treating disorders responsive to relaxation of smooth muscle such as asthma, irritable bowel syndrome, male erectile dysfunction and urinary incontinence. Excerpt(s): This is a non-provisional application which claims the benefit of U.S. Provisional Application No. 60/336,865 filed Nov. 2, 2001. The present invention is directed to novel 2phenyl-5thiophenyl-2,4-- dihydro-[1,2,4]-triazol-3-one derivatives which are smooth muscle relaxants and therefore are useful in treating disorders responsive to relaxation of smooth muscle such as asthma, irritable bowel syndrome, male erectile dysfunction and particularly urinary incontinence. The present invention is also directed to a method of treatment with the novel compounds and to pharmaceutical compositions containing them. Urinary incontinence is a common condition that is the frequent cause of confinement to nursing homes among the elderly. It afflicts significant numbers among both men and women and all ages. In addition studies show some degree of daily incontinence reported among as many as 17% of young apparently healthy women. Safe and reliable methods for treating incontinence are clearly needed. Urinary incontinence is a manifestation of the failure to control the muscles of the bladder or urinary sphincter. Incontinence results when the pressure within the bladder is too great as a result of excessive force exerted by the bladder muscles, or when the sphincter muscles are too weak. Urinary incontinence can be a manifestation of other diseases such as Parkinsonism, multiple sclerosis, lesions of the central nervous system, or bladder infections. Interstitial cysts can result in instability of the bladder detusor muscles and a particularly unpleasant form of urge incontinence. Urinary incontinence is believed to currently affect over 12 million people in the United States alone, and to occur in between 15 and 30% of the population over 60. The current standard of care is quite unsatisfactory. All of the current drugs now utilized to treat urinary incontinence suffer from polypharmacology and unwanted side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treating irrtable bowel syndrome or disease Inventor(s): Cadwallader, Dianne; (Auckland, NZ), Heatley, Craig Leonard; (Auckland, NZ), Meakin, Timothy David; (Auckland, NZ) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030171432 Date filed: March 27, 2003 Abstract: The treatment of humans or other mammals for irritable bowel syndrome (IBS) or irritable bowel disease (IBD) using dosage forms or compositions that include cetyl myristate alone or (in admixture or serially) both cetyl myristate and cetyl palmitate. Excerpt(s): The present invention relates to a method of treatment and/or prophylaxis of irritable bowel syndrome (IBS) and irritable bowel disease (IBD). IBS is a medical condition in which the gut functions improperly because of increased sensitivity to pain and abnormal movements. Symptoms may include abdominal discomfort or pain, often in association with urgency and diarrhea and/or constipation; bloating, spasms and painful cramping. Some hypersensitivity can be triggered by inflammation, as seen in dysentery. Colonic inflammation in can be prolonged by emotional stress. IBD, this is also referred to as, Crohns and Colitis is a disorder involving inflammation and possible ulceration of the digestive tract. Symptoms include diarrhea, fever, anorexia, weight loss, gas, and abdominal tenderness. There may be bloody diarrhea if intestinal bleeding occurs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of abnormal increases in gastrointestinal motility with (R)-verapamil Inventor(s): Devane, John; (Althlone, IE), Kelly, John; (Dublin, IE) Correspondence: Finnegan, Henderson, Farabow; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030092765 Date filed: September 27, 2002 Abstract: The present invention is directed to methods of treating, preventing, and/or managing abnormal increases in gastrointestinal motility, and intestinal conditions that cause the same. Such conditions include, but are not limited to, irritable bowel syndrome (IBS), infectious diseases of the small and large intestines, and symptoms of any of the foregoing. In particular, the present invention discloses methods of using (R)verapamil, as well as compositions and formulations containing the same. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/335,959, filed Nov. 15, 2001, the entire disclosure of which is incorporated herein by reference. The present invention is generally directed to methods of treating, preventing, and/or managing abnormal increases in gastrointestinal motility. Such abnormal increases may be caused by one or more intestinal conditions, including, but not limited to, irritable bowel syndrome (IBS), infectious diseases of the small and large intestine, and symptoms of any of the foregoing. In particular, the invention relates to methods of treating, preventing, and/or managing abnormal increases in gastrointestinal motility with stereo-specific forms of calcium channel blockers, including but not limited to, (R)-

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verapamil. Irritable Bowel Syndrome (IBS) results in about 3.5 million physician visits per year, and is the most common diagnosis made by gastroenterologists, accounting for about 25% of all patients diagnosed (Camilleri and Choi, Aliment Pharmacol. Ther., 11(1):3-15, 1997). Individuals afflicted with IBS visit doctors more frequently, enjoy a lower quality of life, and miss work more often relative to those with no bowel symptoms (Drossman et al., Dig. Dis. Sci., 38:1569-1580, 1993). As a consequence, individuals suffering from IBS incur significantly higher health care costs than those without the condition (Talley et al., Gastroenterology, 109:1736-1741, 1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of functional gastrointestinal disorders Inventor(s): Fowler, David; (Cambridge, GB) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20030119916 Date filed: November 18, 2002 Abstract: Tramadol or a pharmaceutically acceptable salt thereof is used in the manufacture of a pharmaceutical preparation for the treatment of functional gastrointestinal disorders such as irritable bowel syndrome. Excerpt(s): The present invention relates to the treatment of functional gastrointestinal (GI) disorders, especially irritable bowel syndrome (IBS). In particular the present invention relates to pharmaceutical preparations containing tramadol for the treatment of such disorders and the use of tramadol in the manufacture of such preparations. Tramadol (2-[(Dimethylamino) methyl]-1-(3-methoxy phenyl) cyclohexanol is a nonnarcotic opioid analgesic which was first described in the 1960's (see UK Patent 997399). It was first marketed in Germany in 1977 and subsequently in various countries and by 1980 a total of 34 different tramadol formulations in immediate release oral and injectable form were on the market. In 1996 controlled release preparations containing tramadol were introduced, for example TRAMUNDIN RETARD capsules of Mundipharma GmbH, TRAMAL LONG 100 tablets of Grunenthal GmbH and ZYDOL SR tablets of G D Searle & Co. Ltd. The only medical indication for which the various tramadol products are used is the treatment of moderate to severe pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of visceral pain, E.G., irritable bowel syndrome with nerve-acting agents Inventor(s): Cintron, Lynn; (Menlo Park, CA), Gaeta, Raymond R.; (Sunnyvale, CA) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030119756 Date filed: November 8, 2002 Abstract: Methods are provided for use in treating humans suffering from irritable bowel syndrome. In the subject methods, an effective amount of a nerve-acting agent, e.g., lidocaine, topiramate, mexiletine and gabapentin, etc., is administered to a human

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suffering from irritable bowel syndrome. Also provided are pharmaceutical compositions and kits for use in practicing the subject methods. Excerpt(s): Pursuant to 35 U.S.C.sctn. 119 (e), this application claims priority to the filing date of the U.S. Provisional Patent Application Serial No. 60/338,093 filed Nov. 8, 2001, the disclosure of which is herein incorporated by reference. The field of this invention is visceral pain, i.e., Irritable Bowel Syndrome, and the treatment thereof. Visceral pain affects the viscera, such as the intestines. One common type of visceral pain is Irritable Bowel Syndrome (IBS). IBS is a functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habits. IBS has elements of an intestinal motility disorder, a visceral sensation disorder, and a central nervous disorder. While the symptoms of IBS have a physiological basis, no clear mechanism unique to IBS has been identified. Rather, the same mechanisms that cause occasional abdominal discomfort in healthy individuals seem to operate to produce the symptoms of IBS. The symptoms of IBS are therefore a product of quantitative differences in the motor reactivity of the intestinal tract, and increased sensitivity to stimuli or spontaneous contractions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of 5-HT4 modulators for the manufacture of a medicament for the treatment of the bladder diseases Inventor(s): Sanger, Gareth John; (Essex, GB), Wardle, Kay Alison; (Essex, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - UW 2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030045452 Date filed: September 27, 2002 Abstract: A compound which acts as an antagonist at 5-HT.sub.4 receptors is of potential use in the treatment of conditions associated with bladder hypersensitivity, such as urinary incontinence, which is often associated with irritable bowel syndrome (IBS) and a compound which acts as an agonist at 5-HT.sub.4 receptors is of potential use in the treatment of conditions associated with a poorly functioning bladder, such as urinary bladder hypoactivity following prostectomy. Excerpt(s): This invention relates to treatment of conditions associated with bladder hypersensitivity, and conditions associated with a poorly functioning bladder. European Journal of Pharmacology 146 (1988), 187-188, and Naunyn-Schmiedeberg's Arch. Pharmacol. (1989) 340:403-410, describe a non classical 5-hydroxytryptamine receptor, now designated the 5-HT.sub.4 receptor, and that tropisetron (ICS 205-930), which is also a 5-HT.sub.3 receptor antagonist, acts as an antagonist at this receptor and metoclopramide is an agonist at this receptor. WO 91/16045 (SmithKline and French Laboratories Limited) describes the use of cardiac 5-HT.sub.4 receptor antagonists in the treatment of atrial arrhythmias and stroke. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of isatin derivatives as ion channel activating agents Inventor(s): Ahring, Philip K.; (Bagsvard, DK), Christophersen, Palle; (Ballerup, DK), Jensen, Bo Skaaning; (Kobenhavn S., DK), Jorgensen, Tino Dyhring; (Solrod Strand, DK), Olesen, Soren Peter; (Klampenborg, DK), Strobaek, Dorte; (Farum, DK), Teuber, Lene; (Varlose, DK) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030114513 Date filed: October 16, 2002 Abstract: The present invention relates to ion channel activating agents. More particularly, the present invention relates to a particular class of chemical compounds that has proven useful as openers of SKCa and IKCa channels. In further aspects, the present invention relates to the use of these SK/IK channel activating agents for the manufacture of medicaments and pharmaceutical compositions comprising the SK/IK channel activating agents. The SK/IK channel activating agents of the invention are useful for the treatment or alleviation of diseases and conditions associated with the SK/IK channels, in particular respiratory diseases such as asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhea, ischaemia, cerebral ischaemia, ischaemic heart disease, angina pectoris, coronary heart disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Excerpt(s): The present invention relates to ion channel activating agents. More particularly, the present invention relates to a particular class of chemical compounds that has proven useful as openers of SK.sub.Ca and IK.sub.Ca channels. In further aspects, the present invention relates to the use of these SK/IK channel activating agents for the manufacture of medicaments, and pharmaceutical compositions comprising the SK/IK channel activating agents. The SK/IK channel activating agents of the invention are useful for the treatment or alleviation of diseases and conditions associated with the SK/IK channels, in particular respiratory diseases such as asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labour, baldness, cancer, and immune suppression. Ion channels are transmembrane proteins, which catalyse the transport of inorganic ions across cell membranes. The ion channels participate in processes as diverse as the generation and timing of action potentials, synaptic transmissions, secretion of hormones, contraction of muscles, etc.

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

Use of Lactobacillus salivarius Inventor(s): Collins, John Kevin; (Doughcloyne, IE), O'Mahony, Liam; (Cork, IE), O'Sullivan, Gerald Christopher; (Cork, IE), Shanahan, Fergus; (Kinsale, IE) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030166257 Date filed: September 12, 2002 Abstract: Lactobacillus salivarius is useful in the prophylaxis or treatment of undesirable inflammatory activity, especially gastrointestinal inflammatory activity such as inflammatory bowel disease or irritable bowel syndrome. The inflammatory activity may also be due to cancer. The Lactobacillus salivarius is of human origin isolated from resected and washed human gastrointestinal tract. One such strain is UCC 118 described in WO-A-9835014. Excerpt(s): The invention relates to the use of strains of Lactobacillus salivarius. The defence mechanisms to protect the human gastrointestinal tract from colonisation by intestinal bacteria are highly complex and involve both immunological and nonimmunological aspects (V. J. McCracken and H. R. Gaskins, `Probiotics a critical review`, Horizon Scientific Press, UK, 1999, p. 278.). Innate defence mechanisms include the low pH of the stomach, bile salts, peristalsis, mucin layers and anti-microbial compounds such as lysozyme (D. C. Savage, `Microbial Ecology of the Gut`, Academic Press, London, 1997, p.278.). Immunological mechanisms include specialised lymphoid aggregates, underlying M cells, called peyers patches which are distributed throughout the small intestine and colon (M. F. Kagnoff. Gastroenterol. 1993, 105, 1275). Luminal antigens presented at these sites result in stimulation of appropriate T and B cell subsets with establishment of cytokine networks and secretion of antibodies into the gastrointestinal tract (M. R. Neutra and J-P Kraehenbuhl, `Essentials of mucosal immunology`, Academic Press, San Diego, 1996, p.29., M. E. Lamm. Ann. Rev. Microbiol. 1997, 51, 311). In addition, antigen presentation may occur via epithelial cells to intraepithelial lymphocytes and to the underlying lamina propria immune cells (S. Raychaudhuri et al. Nat Biotechnol., 1998, 16, 1025). Therefore, the host invests substantially in immunological defence of the gastrointestinal tract. However, as the gastrointestinal mucosa is the largest surface at which the host interacts with the external environment, specific control mechanisms must be in place to regulate immune responsiveness to the 100 tons of food which is handled by the gastrointestinal tract over an average lifetime (F. Shanahan, `Physiology of the gastrointestinal tract`, Raven Press, 1994, p.643.). Furthermore, the gut is colonised by over 500 species of bacteria numbering 10.sup.11-10.sup.12/g in the colon. Thus, these control mechanisms must be capable of distinguishing non-pathogenic adherent bacteria from invasive pathogens which would cause significant damage to the host In fact, the intestinal flora contributes to defence of the host by competing with newly ingested potentially pathogenic microorganisms. Consumption of non-pathogenic, or probiotic, bacteria has resulted in enhancement of immune parameters in healthy volunteers. Examples of these immune modulatory effects are given in Table 1. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of recombinant gastric lipase for treating functional dyspepsia Inventor(s): Berna, Patrick; (Palaiseau, FR), Milano, Stephane; (St. Nicier, FR) Correspondence: Palmer & Dodge, Llp; Kathleen M. Williams; 111 Huntington Avenue; Boston; MA; 02199; US Patent Application Number: 20030157087 Date filed: October 25, 2002 Abstract: The invention relates to a method for treating a functional dyspepsia by administering to a mammal in need thereof a preparation comprising a recombinant gastric lipase. The invention also relates to pharmaceutical compositions comprising a recombinant gastric lipase and methods of use. Excerpt(s): This application claims priority under 35 U.S.C.sctn.120 to International Application PCT/EPO1/04679, filed Apr. 25, 2001 which claims priority to 00401174.8, filed Apr. 27, 2000. The invention relates to the use of recombinant gastric lipase for the preparation of a drug for preventing and/or treating functional dyspepsia. The invention also concerns a method for treating functional dyspepsia comprising administering to a patient in need thereof an effective amount of the above compound. Dyspepsia is a very common syndrome that accounts for about 30% of cases seen by gastroenterologists. Functional dyspepsia (also known as non-ulcer dyspepsia or NUD, i.e. without any clear and obvious gastric lesion) is the most important etiologic category and represents about 60% of all dyspepsia cases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of rofleponide in the treatment of irritable bowel syndrome (ibs) Inventor(s): Brattsand, Ralph; (Lund, SE) Correspondence: White & Case Llp; Patent Department; 1155 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030004214 Date filed: July 19, 2002 Abstract: The invention provides the use of rofleponide, its esters and salts in the manufacture of a medicament for use in the treatment of irritable bowel syndrome (IBS) and pharmaceutical formulations for use in such treatment. Excerpt(s): The present invention provides a new treatment for irritable bowel syndrome (IBS), namely use of rofleponide, its esters and salts. The irritable bowel syndrome is a chronic abdominal disease for which there is no apparent underlying structural cause. Symptoms in IBS are thought to arise from altered gastro-intestinal motility, increased visceral sensitivity or altered brain-gut modulation. The diagnosis of IBS is hampered by the absence of simple diagnostic tests. Physicians approach IBS as a diagnosis of exclusion and then base the diagnosis on certain diagnostic criteria such as abnormal discomfort and pain, bloating and disturbed defecation, see further in Gut, 1999; 45 (Suppl.2):II43, C1(Sept), Thompson et al., and Gasteroenterology 1997, vol. 112, p.2120-2137. Current treatment of IBS is mainly antispasmodics, laxatives, loperamide and antidepressants. A history of gastro-enteritis (Salmonella, Campylobacter etc.) is more commonly found in patients with IBS than in a control population and up to 30% of patients develop IBS after gastro-enteritis. According to the invention there is provided the use of rofleponide, its esters and salts, such as fatty acid esters e.g.

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rofleponide palmitate in the manufacture of a medicament for use in the treatment of irritable bowel syndrome, particularly post-infectious irritable bowel syndrome. 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 irritable bowel syndrome, 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 “irritable bowel syndrome” (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 irritable bowel syndrome. You can also use this procedure to view pending patent applications concerning irritable bowel syndrome. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON IRRITABLE BOWEL SYNDROME Overview This chapter provides bibliographic book references relating to irritable bowel syndrome. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on irritable bowel syndrome 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 “irritable bowel syndrome” (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 irritable bowel syndrome: •

Breaking the Bonds of Irritable Bowel Syndrome: A Psychological Approach to Regaining Control of Your Life Source: Oakland, CA: New Harbinger Publications, Inc. 2000. 177 p. Contact: Available from New Harbinger Publications, Inc. 5674 Shattuck Avenue, Oakland, California 94609. (800) 748-6273 or (510) 652-0215. Fax: (510) 652-5472. E-mail: [email protected]. Website: http://www.newharbinger.com/contactus.htm. PRICE: $14.95 and handling. ISBN: 1572241888. Summary: Irritable bowel syndrome (IBS) consists of recurrent episodes of abdominal pain related to altered bowel habit, which may consist of predominantly constipation or diarrhea, or an alternation between the two. In this book, the author encourages an open discussion of the symptoms and feelings that accompany irritable bowel syndrome

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(IBS). Charts and worksheets help readers track the relationship between unpleasant symptoms and external triggers such as foods, stressful events, emotional states, and certain thoughts. By using these tools and improving their emotional awareness, readers will benefit their overall mental health, gain a tremendous sense of accomplishment, and regain a feeling of being in charge of their life. Coping skills, such as relaxation exercises and assertiveness techniques, teach readers how to manage their stress more effectively and help them break free of the restrictions placed upon them by the disruptiveness of this digestive disorder. The book includes ten chapters, a section of references, and a brief list of resources for additional information. •

Irritable Bowel Syndrome (IBS) and Gastrointestinal Solutions Handbook Source: Encinitas, CA: United Research Publishers. 1997. 232 p. Contact: Available from United Research Publishers. Department RB-91, 103 North Coast Highway 101, Encinitas, CA 92024. PRICE: $14.95. ISBN: 096149249X. Summary: This book discusses irritable bowel syndrome (IBS) and other gastrointestinal problems and explains how readers can educate themselves, treat problems, and prevent recurrences of these conditions. The author discusses natural, alternative, and medical remedies that can bring relief without the use of drugs. The author also explains how the gastrointestinal system works, why certain foods, activities, and stress cause problems, and why over 20 million Americans deal with IBS and gastrointestinal distress. One chapter in the book discusses other diseases of the digestive tract and notes that they require a doctor's attention but are often easier to treat than IBS. IBS, however, can be individualistic, intermittent, and difficult to treat. The last section reviews some nontraditional helps and ideas that might be of use, including homeopathy, relaxation, hypnotherapy, aromatherapy, herbal remedies, and acupuncture. A final chapter lists fat grams and calories for many common foods.

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I.B.S. Relief: A Doctor, a Dietitian, and a Psychologist Provide a Team Approach to Managing Irritable Bowel Syndrome Source: Somerset, NJ: John Wiley and Sons, Inc. 1998. 176 p. Contact: Available from John Wiley and Sons, Inc. Distribution Center, 1 Wiley Drive, Somerset, NJ 08875-1272. (800) 225-5945 or (732) 469-4400. Fax (732) 302-2300. E-mail: [email protected]. Website: www.wiley.com. PRICE: $13.95 plus shipping and handling. ISBN: 0471347418. Summary: This book offers a multidisciplinary approach to managing irritable bowel syndrome (IBS). The authors note that because the complex nature of IBS may raise medical, nutrition, and psychological issues, a gastroenterologist, registered dietitian, and psychologist collaborated to write the book. The book is designed as a workbook for people with IBS to learn symptom management skills. The authors stress that successful management of IBS symptoms requires matching management strategies to the links between diet, stress, and symptoms that are specific to each individual. The first two chapters focus on diagnosing IBS. Additional chapters cover the causes of IBS, the importance of a healthy diet, dietary aggravators, diet adjustments for specific symptoms, stress management, coping with pain, managing IBS when other disease processes are present, and working with one's health care providers. The book includes self assessments, recordkeeping forms, and six different diet plans (to be used alone or in combination). The book includes a list of ten tips for living with an irritable bowel, and appendices that cover the physiology of the gut, Canada's food guide, high fiber and low fat recipes, and resources. The book concludes with a subject index.

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Tell Me What to Eat If I Have Irritable Bowel Syndrome: Nutrition You Can Live With Source: Franklin Lakes, NJ: Career Press, Inc. 2000. 137 p. Contact: Available from Career Press, Inc. 3 Tice Road, P.O. Box 687, Franklin Lakes, NJ 07417. (800) 227-3371. Website: www.careerpress.com or www.newpagebooks.com. PRICE: $10.99 plus shipping and handling. Summary: This book offers eating and nutrition guidelines for people who have been diagnosed with irritable bowel syndrome (IBS). People with IBS have bowels that tend to overreact in certain situations. Whatever affects the bowels of the population at large, such as diet, hormones, or stress, affects those of people with IBS even more, resulting in the symptoms of the disorder. This book suggests an approach to managing IBS that includes eating a healthful diet (rich in high fiber foods that the patient can tolerate), drinking plenty of water, avoiding foods that make symptoms worse, and finding ways to minimize and handle the stress of daily living. The author cautions that treating IBS is like trying to hit a moving target; not only do IBS symptoms vary from one person to the next, they can also change from week to week in the same person. Similarly, different treatments work for different people and some treatments used for one symptom can cause a completely new symptom to occur. This book emphasizes the possible dietary treatments for IBS. The author notes that people with IBS who do not seem to respond well to drugs or dietary modification may want to concentrate on the psychological treatments available for IBS. The book offers seven chapters that cover common questions about IBS ('everything you ever wanted to ask a gastroenterologist'), the main symptoms of IBS, working with a dietitian to manage IBS, ten food steps to freedom, 20 recommended recipes, food shopping guidelines, and eating out at restaurants. The ten food steps include keep an FFS (food, feelings, symptoms) diary, eat high fiber foods, drink eight or more 8 ounce glasses of water, limit caffeine, avoid high fat meals and snacks, avoid trouble spice, avoid overdoing alcohol, avoid gassy foods, eat smaller more frequent meals, and exercise. A brief subject index concludes the book.

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Irritable Bowel Syndrome and the Mind-Body Brain-Gut Connection Source: Columbus, OH: Parkview Publishing. 1997. 302 p. Contact: Available from Parkview Publishing. P.O. Box 1103, Columbus, OH 43216. (888) 599-6464 or (614) 258-4848. Fax (614) 258-7272. PRICE: $19.95. ISBN: 0965703894. Summary: This book offers readers a guide to understanding and treating their functional gastrointestinal (GI) disorders, focusing on irritable bowel syndrome (IBS). The author emphasizes the role that individuals can play in managing their own symptoms and future. The book is framed around eight steps to positive change; eight chapters cover the GI tract and the mind-body connection; the common functional GI disorders; healing with diagnosis and education; understanding one's own symptoms and GI tract; identifying gut 'triggers'; emphasizing self-care and wellness; taking action if symptoms persist; and managing the functional GI disorder. Specific topics include the interplay between stress, psychology and symptoms; colitis and inflammatory bowel disease (IBD); the International Foundation for Functional Gastrointestinal Disorders (IFFGD); self-tests for personal and psychological problems; the role of a history of abuse; cognitive behavioral factors; food and symptom diaries; food allergy versus food intolerance and sensitivity; inflammation and infection; the menstrual cycle; seasonal changes; nutrition; weight; exercise; the impact of alcohol, nicotine, and tobacco; the use of an elimination diet; stress, emotional, and psychological issues; chronic pain management; and managing the symptoms of chest pain, heartburn, dysphagia,

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dyspepsia, nausea, vomiting, aerophagia (burping and belching), abdominal bloating, rectal gas and flatulence, abdominal pain, diarrhea, constipation, bowel incontinence, and anal and rectal pain. The book includes black and white photographs, charts, and figures; a subject index concludes the volume. •

Relief from IBS: Irritable Bowel Syndrome Source: New York, NY: Ballantine Books. 1991. 216 p. Contact: Available from Ballantine Books. Mail Sales Department, Department 05001, Random House Distribution Center, 400 Hahn Road, Westminster, MD 21157. (800) 7932665 or (410) 848-1900. Fax (800) 659-2436 or (410) 386-7049. PRICE: $5.99 (paperback). ISBN: 0871315572. Summary: This comprehensive, practical text for patients with irritable bowel syndrome (IBS) provides information about understanding and managing IBS. The text is divided into four sections: characteristics of IBS (background information on IBS symptoms and the digestive system); risk factors (combinations of diet and emotions which seem to trigger IBS); tools for tracking IBS status (diet detection diaries; mood mapping); and IBS treatment (life style changes; coping skills; relaxation techniques; biofeedback; effective diet planning; medications). The text emphasizes what IBS patients can do for themselves, providing realistic, practical guidelines for controlling IBS symptoms and obtaining lasting relief. Answers to common questions asked about IBS, information concerning children with IBS, and references for further reading are appended.

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

25 Natural Ways to Control Irritable Bowel Syndrome by James Scala; ISBN: 0658007017; http://www.amazon.com/exec/obidos/ASIN/0658007017/icongroupinterna

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A Guide to Therapy for Irritable Bowel Syndrome by Leonard Weinstock, Thomas Lipsitz; ISBN: 0970712502; http://www.amazon.com/exec/obidos/ASIN/0970712502/icongroupinterna

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A Meditaion to Help With Irritable Bowel Syndrome & Inflammatory Bowel Disease by Belleruth Naparstek (2002); ISBN: 1881405605; http://www.amazon.com/exec/obidos/ASIN/1881405605/icongroupinterna

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A Victim No More: Overcoming Irritable Bowel Syndrome by Jonathan M. Berkowitz (2003); ISBN: 1591200784; http://www.amazon.com/exec/obidos/ASIN/1591200784/icongroupinterna

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All About Irritable Bowel Syndrome by David Potterton; ISBN: 0572021658; http://www.amazon.com/exec/obidos/ASIN/0572021658/icongroupinterna

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Behavioral Medicine and Irritable Bowel Syndrome by Paul R. Latimer (1982); ISBN: 0080250858; http://www.amazon.com/exec/obidos/ASIN/0080250858/icongroupinterna

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Breaking the Bonds of Irritable Bowel Syndrome: A Psychological Approach to Regaining Control of Your Life by Barbara Bradley Bolen Ph.D., W. Grant Thompson (2000); ISBN: 1572241888; http://www.amazon.com/exec/obidos/ASIN/1572241888/icongroupinterna

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Clinical Implications of Irritable Bowel Syndrome by Philippe Denis (Editor) (1998); ISBN: 3110158604; http://www.amazon.com/exec/obidos/ASIN/3110158604/icongroupinterna

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Cognitive-Behavioral Treatment of Irritable Bowel Syndrome: The Brain-Gut Connection by Brenda B. Toner (Editor), et al; ISBN: 157230135X; http://www.amazon.com/exec/obidos/ASIN/157230135X/icongroupinterna

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Contemporary Diagnosis and Management of Irritable Bowel Syndrome by Douglas A. Drossman, Anthony J. Lembo; ISBN: 188406597X; http://www.amazon.com/exec/obidos/ASIN/188406597X/icongroupinterna

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Diets to Help Colitis and Irritable Bowel Syndrome: Natural Relief With a Carefully Balanced Regime by J. O. Lay; ISBN: 0722531990; http://www.amazon.com/exec/obidos/ASIN/0722531990/icongroupinterna

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Digestion, Diet, and Disease: Irritable Bowel Syndrome and Gastrointestinal Function by Janice M. Vickerstaff Joneja (2004); ISBN: 0813533872; http://www.amazon.com/exec/obidos/ASIN/0813533872/icongroupinterna

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Diseases Explained: Irritable Bowel Syndrome Wall Chart by Lexi-Comp; ISBN: 1930598203; http://www.amazon.com/exec/obidos/ASIN/1930598203/icongroupinterna

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Freedom from Digestive Distress: Medicine-Free Relief from Heartburn, Gas, Bloating, and Irritable Bowel Syndrome by Gary L. Gitnick, Karen Cooksey (2000); ISBN: 0812932625; http://www.amazon.com/exec/obidos/ASIN/0812932625/icongroupinterna

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Functional Dyspepsia and Irritable Bowel Syndrome - Concepts and Controversies by H. Goebell (Editor), et al (1998); ISBN: 079238735X; http://www.amazon.com/exec/obidos/ASIN/079238735X/icongroupinterna

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Gastrointestinal Health : A Self-Help Nutritional Program to Prevent, Cure, or Alleviate Irritable Bowel Syndrome, Ulcers, Heartburn, Gas, Constipation by Steven R. Peikin; ISBN: 0060984058; http://www.amazon.com/exec/obidos/ASIN/0060984058/icongroupinterna

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Gastrointestinal Health Third Edition : The Proven Nutritional Program to Prevent, Cure, or Alleviate Irritable Bowel Syndrome (IBS), Ulcers, Gas, Constipation, Heartburn, and Many Other Digestive Disorders by Steven R. Peikin (Author); ISBN: 0060585323; http://www.amazon.com/exec/obidos/ASIN/0060585323/icongroupinterna

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Health Journeys: A Meditation to Help with Irritable Bowel Syndrome & Inflammatory Bowel Disease by Belleruth Naparstek, Steven M. Kohn; ISBN:

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1881405508; http://www.amazon.com/exec/obidos/ASIN/1881405508/icongroupinterna •

Healthy Digestion the Natural Way: Preventing and Healing Heartburn, Constipation, Gas, Diarrhea, Inflammatory Bowel and Gallbladder Diseases, Ulcers, Irritable Bowel Syndrome, and More by D. Lindsey Berkson (Author) (2000); ISBN: 0471349623; http://www.amazon.com/exec/obidos/ASIN/0471349623/icongroupinterna

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Herbal Remedies: Irritable Bowel Syndrome (Health Know How) by David Potterson; ISBN: 0572018185; http://www.amazon.com/exec/obidos/ASIN/0572018185/icongroupinterna

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HOUGHTON IRRITABLE BOWEL SYNDROME VOLUME 13 ISS 3; ISBN: 0702024996; http://www.amazon.com/exec/obidos/ASIN/0702024996/icongroupinterna

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How to Cope Successfully with Irritable Bowel Syndrome (How to Cope Successfully With.) by Richard Emerson, Alastair Forbes; ISBN: 1903784069; http://www.amazon.com/exec/obidos/ASIN/1903784069/icongroupinterna

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I.B.S. Relief: A Doctor, a Dietitian, and a Psychologist Provide a Team Approach to Managing Irritable Bowel Syndrome by Dawn Burstall (Author), et al; ISBN: 0471347418; http://www.amazon.com/exec/obidos/ASIN/0471347418/icongroupinterna

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IBS Breakthrough : Healing Irritable Bowel Syndrome for Good With Chinese Medicine by Leigh Fortson, Bing Lee (2001); ISBN: 1931412626; http://www.amazon.com/exec/obidos/ASIN/1931412626/icongroupinterna

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Ibs Handbook: Learning to Live With Irritable Bowel Syndrome by Gerard L Guillory, Mike Snipes; ISBN: 0962253308; http://www.amazon.com/exec/obidos/ASIN/0962253308/icongroupinterna

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IBS: a Complete Guide to Irritable Bowel Syndrome by Christine P. Dancey, Susan Backhouse; ISBN: 1854879103; http://www.amazon.com/exec/obidos/ASIN/1854879103/icongroupinterna

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Irritable Bowel Syndrome by Nicholas W. Read (Editor); ISBN: 0808916696; http://www.amazon.com/exec/obidos/ASIN/0808916696/icongroupinterna

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Irritable Bowel Syndrome by P. Denis (Editor); ISBN: 3110149125; http://www.amazon.com/exec/obidos/ASIN/3110149125/icongroupinterna

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Irritable Bowel Syndrome by Sarah, Dr. Brewer; ISBN: 0722533926; http://www.amazon.com/exec/obidos/ASIN/0722533926/icongroupinterna

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Irritable Bowel Syndrome & the Mind-Body/Brain-Gut Connection: 8 Steps for Living a Healthy Life with a Functional Bowel Disorder or Colitis; ISBN: 0965703894; http://www.amazon.com/exec/obidos/ASIN/0965703894/icongroupinterna

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Irritable Bowel Syndrome (Fast Facts) by W Grant Thompson, Kenneth W. Heaton (2004); ISBN: 1899541977; http://www.amazon.com/exec/obidos/ASIN/1899541977/icongroupinterna

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Irritable Bowel Syndrome (Food Solutions):: Recipes and Advice to Control Symptoms by Patsy Westcott, Philip Wilson (Illustrator) (2002); ISBN: 0600604950; http://www.amazon.com/exec/obidos/ASIN/0600604950/icongroupinterna

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Irritable bowel syndrome (SuDoc HE 20.3323:IR 7/999) by U.S. Dept of Health and Human Services; ISBN: B000111E4E; http://www.amazon.com/exec/obidos/ASIN/B000111E4E/icongroupinterna

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Irritable Bowel Syndrome (What You Really Need to Know About.) by Howard; ISBN: 1840283459; http://www.amazon.com/exec/obidos/ASIN/1840283459/icongroupinterna

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Irritable Bowel Syndrome [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3ON; http://www.amazon.com/exec/obidos/ASIN/B00008R3ON/icongroupinterna

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Irritable Bowel Syndrome and Diverticulosis: A Self-Help Plan by Shirley Trickett, Belinda Dawes; ISBN: 0722538618; http://www.amazon.com/exec/obidos/ASIN/0722538618/icongroupinterna

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Irritable Bowel Syndrome and the MindBodySpirit Connection: 7 Steps for Living a Healthy Life With a Functional Bowel Disorder, Crohn's Disease or Colitis by William B. Salt II, Neil F. Neimark (2002); ISBN: 0965703851; http://www.amazon.com/exec/obidos/ASIN/0965703851/icongroupinterna

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Irritable Bowel Syndrome: A Natural Approach by Rosemary Nicol (1999); ISBN: 1569751889; http://www.amazon.com/exec/obidos/ASIN/1569751889/icongroupinterna

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Irritable Bowel Syndrome: A Practical Guide (Mandarin Paperback) by Geoff Watts; ISBN: 074932466X; http://www.amazon.com/exec/obidos/ASIN/074932466X/icongroupinterna

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Irritable Bowel Syndrome: Diagnosis and Treatment by Michael Camilleri, et al; ISBN: 0702026557; http://www.amazon.com/exec/obidos/ASIN/0702026557/icongroupinterna

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Irritable Bowel Syndrome: How Your Diet Can Help by Stephen Terrass; ISBN: 0722531516; http://www.amazon.com/exec/obidos/ASIN/0722531516/icongroupinterna

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Irritable Bowel Syndrome: New Ideas and Insights into Pathophysiology by N.W. Read (Editor); ISBN: 0632025557; http://www.amazon.com/exec/obidos/ASIN/0632025557/icongroupinterna

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Irritable Bowel Syndrome: One Disease, Several, or None? (Perspectives in Digestive Diseases, Vol. 5) by G. Bianchi Porro, N.W. Read (Editor); ISBN: 8877490616; http://www.amazon.com/exec/obidos/ASIN/8877490616/icongroupinterna

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Irritable Bowel Syndrome: Pocketbook by Roger Jones (2001); ISBN: 185317985X; http://www.amazon.com/exec/obidos/ASIN/185317985X/icongroupinterna

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Irritable Bowel Syndrome: Psychosocial Assessment and Treatment by Edward B. Blanchard; ISBN: 1557987300; http://www.amazon.com/exec/obidos/ASIN/1557987300/icongroupinterna

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Irritable Bowel Syndrome: Special Diet Cookbook by Ann Page-Wood, Jill Davies; ISBN: 0722523440; http://www.amazon.com/exec/obidos/ASIN/0722523440/icongroupinterna

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Overcoming Irritable Bowel Syndrome by Christine Dancey, et al; ISBN: 1854871757; http://www.amazon.com/exec/obidos/ASIN/1854871757/icongroupinterna

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Recipes for Health: Irritable Bowel Syndrome: Over 100 Recipes for Coping With This Digestive Disorder by Ann Page-Wood, et al; ISBN: 0722531419; http://www.amazon.com/exec/obidos/ASIN/0722531419/icongroupinterna

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Relief from Ibs: Irritable Bowel Syndrome by Elaine F. Shimberg; ISBN: 034536712X; http://www.amazon.com/exec/obidos/ASIN/034536712X/icongroupinterna

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Stop Belly-Aching: Banish Indigestion & Irritable Bowel Syndrome by Peter, Dr Mansfield, Dr. Peter Mansfield (2002); ISBN: 0285636189; http://www.amazon.com/exec/obidos/ASIN/0285636189/icongroupinterna

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Tell Me What to Eat If I Have Irritable Bowel Syndrome: Nutrition You Can Live With (Tell Me What to Eat) by Elaine Magee (2000); ISBN: 1564144445; http://www.amazon.com/exec/obidos/ASIN/1564144445/icongroupinterna

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The 2002 Official Patient's Sourcebook on Irritable Bowel Syndrome: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833966; http://www.amazon.com/exec/obidos/ASIN/0597833966/icongroupinterna

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The Bible Cure for Irritable Bowel Syndrome (Bible Cure Series) by Don, MD Colbert (2002); ISBN: 0884198278; http://www.amazon.com/exec/obidos/ASIN/0884198278/icongroupinterna

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The First Year - IBS (Irritable Bowel Syndrome): An Essential Guide for the Newly Diagnosed by Heather Van Vorous, David B. Posner (Foreword); ISBN: 1569245479; http://www.amazon.com/exec/obidos/ASIN/1569245479/icongroupinterna

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The Irritable Bowel Syndrome (Ibs) and Gastrointestinal Solutions Handbook by Chet Cunningham (1997); ISBN: 096149249X; http://www.amazon.com/exec/obidos/ASIN/096149249X/icongroupinterna

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The Irritable Bowel Syndrome Sourcebook by Laura O'Hare; ISBN: 0737305533; http://www.amazon.com/exec/obidos/ASIN/0737305533/icongroupinterna

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The Natural Way With Irritable Bowel Syndrome (Natural Way) by Nigel Howard; ISBN: 1852305835; http://www.amazon.com/exec/obidos/ASIN/1852305835/icongroupinterna

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The Psychopathology of Functional Somatic Syndromes: Neurobiology and Illness Behavior in Chronic Fatigue Syndrome, Fibromyalgia, Gulf War Illness, Irritable Bowel Syndrome, and Premenstrual Syndrome by Peter, Md. Manu (2004); ISBN: 078901260X; http://www.amazon.com/exec/obidos/ASIN/078901260X/icongroupinterna

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The Troubled Gut: Self Help for Irritable Bowel Syndrome (Headline Health Kicks) by Barbara Rowlands; ISBN: 0747243867; http://www.amazon.com/exec/obidos/ASIN/0747243867/icongroupinterna

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The Wellness Book of I.B.S.: How to Achieve Relief from Irritable Bowel Syndrome and Live a Symptom-Free Life by Deralee Scanlon, Barbara Cottman Becnel (Contributor); ISBN: 0312852266; http://www.amazon.com/exec/obidos/ASIN/0312852266/icongroupinterna

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Understanding Irritable Bowel Syndrome by Simon Darnley (Author), Barbara Millar (Author); ISBN: 0470844965; http://www.amazon.com/exec/obidos/ASIN/0470844965/icongroupinterna

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Understanding Irritable Bowel Syndrome by Kieran Horiarty; ISBN: 1898205612; http://www.amazon.com/exec/obidos/ASIN/1898205612/icongroupinterna

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What is irritable bowel syndrome? (SuDoc HE 20.3323:IR 7/990) by U.S. Dept of Health and Human Services; ISBN: B000102XTU; http://www.amazon.com/exec/obidos/ASIN/B000102XTU/icongroupinterna

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What You Really Need to Know About Irritable Bowel Syndrome by Rob Buckman, et al; ISBN: 0867308273; http://www.amazon.com/exec/obidos/ASIN/0867308273/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “irritable bowel syndrome” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Irritable bowel syndrome: pathogenesis and treatment Author: Read, N. W.; Year: 1991; Oslo, Norway: Norwegian University Press, c1987

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Psychotherapy in irritable bowel syndrome: a controlled outcome study Author: Svedlund, Jan.; Year: 1987; Copenhagen: Munksgaard, [1983]; ISBN: 8716095960

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Towards confident management of irritable bowel syndrome Author: Heaton, K. W. (Kenneth Willoughby); Year: 1991; Southampton: Duphar Medical Relations, 1991; ISBN: 1870678311

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

Pharmacotherapy of the Irritable Bowel Syndrome Source: in Lewis, J.H., ed. Pharmacologic Approach to Gastrointestinal Disorders. Baltimore, MD: Williams and Wilkins. 1994. p. 163-177.

11

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

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Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4000. Fax (410) 528-4414. PRICE: $85 (as of 1995). ISBN: 0683049704. Summary: In this chapter, from a book on the pharmacologic approach to gastrointestinal disorders, the author explains pharmacotherapy of the irritable bowel syndrome (IBS). The author concentrates on treatment of symptoms involving the small bowel and colon, since these areas evoke most patient complaints. The chapter covers demographic considerations; pathophysiologic features; food intake and IBS symptoms; gas syndromes; diagnostic considerations; treatment options, including psychotherapy, hypnotherapy, and behavior modification; pharmacologic interventions, including pain treatment, anticholinergic agents, treatment of depression and anxiety, the selection of antidepressant medication, and antianxiety agents; and other agents of potential value for painful IBS, including peppermint oil, trimebutine, mebeverine, calcium channel blockers, treatment of diarrhea, and treatment of constipation. 1 figure. 6 tables. 73 references. (AA-M). •

Irritable Bowel Syndrome: Does Making a Confident Diagnosis Reassure an Unhappy Patient? Source: in Barkin, J.S., and Rogers, A.I., eds. Difficult Decisions in Digestive Diseases. 2nd ed. St. Louis, MO: Mosby-Year Book, Inc. 1994. p. 399-404. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 633-6699 or (800) 325-4177 or (314) 872-8370. Fax (314) 432-1380. PRICE: $84 (as of 1995). ISBN: 0801680190. Summary: In this chapter, from a medical text on difficult decisions in digestive diseases, the authors explain irritable bowel syndrome (IBS), focusing on the role of reassurance in the management of IBS. They stress that, for the physician to effectively reassure the patient, both need security that the diagnosis is correct, and the decision to reassure can be a difficult one if the physician is not confident. Topics include differentiating IBS from other gastrointestinal diseases; diagnostic tests used to confirm the IBS diagnosis; the durability of the IBS diagnosis over time; the effectiveness of reassurance as a therapeutic tactic; and the six sequential steps in reassurance therapy. The authors conclude that the benign course of IBS makes reassurance an important initial management approach, but the treatment may have more than time-buying utility in many patients. 3 figures. 4 tables. 23 references. (AA-M).

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Irritable Bowel Syndrome and Constipation Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 496-501. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter from a gastroenterology text covers irritable bowel syndrome (IBS) and constipation. The IBS is a heterogeneous group of functional gastrointestinal tract disorders involving the small intestine and colon; central to the definition of IBS is abdominal pain. The author focuses on patients with IBS who have constipation as their primary bowel complaint. Topics include pathophysiology, diagnosis, definition, history and physical examination, diagnostic tests including those of colonic function, and treatment options, including general measures, treatment for abdominal pain, gas and

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bloating, and psychologic and behavioral therapy. The general treatment measures recommended include developing a therapeutic relationship, providing reassurance and education, and dietary interventions including fiber supplementation. Patients who fail to respond adequately to these general treatment measures should receive additional diagnostic testing and therapy directed at their predominant symptoms. 1 table. 12 references. •

Evidence-Based Therapy of Irritable Bowel Syndrome Source: in Manu, P. Pharmacotherapy of Common Functional Syndromes: EvidenceBased Guidelines for Primary Care Practice. Binghamton, NY: Haworth Medical Press. 2000. p. 175-177. Contact: Available from Haworth Medical Press, an imprint of Haworth Press, Inc. 10 Alice Street, Binghamton, New York 13904-1580. (800) HAWORTH or (800) 429-6784. Outside United States and Canada (607) 722-5857. Fax (800) 895-0582. E-mail: [email protected]. Website: www.haworthpressinc.com. PRICE: $69.95 plus shipping and handling. ISBN: 0789005883. Summary: This chapter is from a book that evaluates drug therapies for each of the four major functional disorders: chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome (IBS), and premenstrual syndrome. In this chapter, the final of six short chapters that focus on IBS, the author reviews evidence based therapy for IBS. The author contradicts present thinking that drug therapy for IBS should focus on the most disturbing symptoms, using loperamide for diarrhea, fiber for constipation, and anticholinergic agents for pain. The author, instead, contends that research studies do not provide support for the effectiveness of these drug approaches. Because evidence indicates that tricyclic antidepressants are effective for the totality of this illness, the author contends that these drugs should constitute the first line treatment in all cases in which the severity of the syndrome warrants intervention, provided that there are no contraindications to the use of these agents and that the potential for drug interactions has been considered. Monotherapy with amitriptyline or desipramine should be initiated with a starting dose of 10 mg administered once a day in patients with the diarrhea predominant variant of the syndrome. Adjunctive therapy with a bulking agent may lead to a decrease in the overall severity of the syndrome in all patients and ease the bowel habit and stool passage in those with the constipation predominant variant of the syndrome.

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Main Symptoms of Irritable Bowel Syndrome Source: in Magee, E. Tell Me What to Eat If I Have Irritable Bowel Syndrome. Franklin Lakes, NJ: Career Press, Inc. 2000. p. 24-29. Contact: Available from Career Press, Inc. 3 Tice Road, P.O. Box 687, Franklin Lakes, NJ 07417. (800) 227-3371. Website: www.careerpress.com or www.newpagebooks.com. PRICE: $10.99 plus shipping and handling. Summary: This chapter is from a book that offers eating and nutrition guidelines for people who have been diagnosed with irritable bowel syndrome (IBS). People with IBS have bowels that tend to overreact in certain situations. Whatever affects the bowels of the population at large, such as diet, hormones, or stress, affects those of people with IBS even more, resulting in the symptoms of the disorder. This chapter describes the main symptoms of IBS, which include abdominal pain, irregular pattern of defecation at least 25 percent of the time, constipation, diarrhea, mucus in the stool, abdominal bloating or swelling, the feeling of incomplete emptying rectum, and gas attacks (flatulence). The

194 Irritable Bowel Syndrome

author notes that, for many women, IBS symptoms seem to worsen during their periods (menstruation). Therefore, right before and during one's period, it is especially important to avoid trigger foods or stressors that seem to bring on or aggravate bowel symptoms. The chapter concludes with a brief discussion of common IBS symptoms that occur in other parts of the body. These can include heartburn, sleep disturbances, fatigue, bladder or urinary problems, non cardiac chest pain, nausea or bloating, pain in the upper abdomen, migraine headaches, painful intercourse, and fibromyalgia. •

Coexistence of Inflammatory Bowel Disease and Irritable Bowel Syndrome Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 87-90. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the coexistence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as IBD. Irritable bowel syndrome (IBS) is a chronic abdominal symptom complex for which no structural underlying abnormality can be demonstrated. It is a common disorder that affects all age groups with an increased frequency in females. Few if any of the clinical features of IBS can confidently distinguish it from IBD. The multiplicity and chronicity of symptoms and their relationship to altered bowel habit can be helpful hints. A psychoneurotic disposition, evidence of anxiety or depression, and a tendency to somatize symptoms referable not only to the gut but other organ systems are pointers in favor of IBS. However, when IBS occurs in a patient with established IBD, this can be a difficult diagnosis. Since IBS is a very common disorder, it is not unexpected to find patients with both IBS and IBD. The author considers whether there is a special relationship between these two disorders. There is good scientific evidence that inflammation of the gut alters its physiologic performance, and this may persist after resolution of the inflammation. The author concludes that IBS occurs with greater frequency in certain patients in remission from IBD, and this is more easily seen in UC than in CD. Symptoms of IBS in the context of IBD are no different from those typical for that condition. An awareness of this relationship is of key importance in making a confident diagnosis, as is a good knowledge of the patients' history and the characteristic behavior of their IBD. In some complicated IBD patients, extensive investigation by colonoscopy with or without small bowel radiography may be required. For most patients, treatment of IBS should follow the usual guidelines with notable exceptions in the case of patients with histories of obstruction. 1 figure. 17 references.

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Irritable Bowel Syndrome: Diagnosis and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 241259. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price.

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Summary: This chapter on the diagnosis and treatment of irritable bowel syndrome (IBS) is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). Irritable bowel syndrome, the most common functional bowel disorder, is characterized by abdominal pain, bloating, and disturbed defecation. The functional gastrointestinal (GI) disorders result in significant utilization of health care resources; IBS is responsible for a considerable economic burden because of the high frequency of physician visits and work absenteeism. After consideration of demographic features, the nature of the symptoms, and the severity index, only limited investigations to rule out organic disease are indicated. The variety of symptoms, the lack of understanding of the pathophysiology of the disease, and the complex interaction of the central nervous system and the enteral nervous system and their receptors, suggest that no single drug will cure IBS. The authors recommend a strong physician-patient relationship to help control health care utilization. The goal should be judicious use of medical testing, within an atmosphere of an empathetic patient-doctor relationship. Recurrences should be treated by a symptom based approach, with careful attention to the psychosocial triggers that contribute to exacerbation. With a few simple investigations (tests), sympathetic explanation (patient education), and appropriate treatment, most patients with IBS have a good prognosis. 4 tables. 124 references. •

Management of the Irritable Bowel Syndrome Source: in Danzi, J.T.; Scopelliti, J.A., eds. Office Management of Digestive Diseases. Malvern, PA: Lea and Febiger. 1992. p. 102-111. Contact: Available from Lea and Febiger. Box 3024, Malvern, PA 19355-9725. (215) 2512230. PRICE: $39.50. ISBN: 0812114361. Summary: This chapter, from a medical textbook about the office management of common gastrointestinal diseases, discusses the management of the irritable bowel syndrome (IBS). Topics include pathogenesis, psychosocial factors, diagnosis, treatment issues, patient education, and specific therapy, including fiber supplements, anticholinergics, tranquilizers, opioids, antidepressants, and psychotherapy. The author stresses that successful treatment requires time, energy, and empathy; the interaction of the physician and the patient constitutes the treatment. 20 references.

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Coexistent Irritable Bowel Syndrome and Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 91-94. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This second chapter on the coexistence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as IBD. Irritable bowel syndrome (IBS) is a chronic abdominal symptom complex for which no structural underlying abnormality can be demonstrated. It is a common disorder that affects all age groups with an increased frequency in females. Few if any of the clinical features of IBS can confidently distinguish it from IBD. This chapter focuses on the prevalence of

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IBS, clinically relevant pathophysiology, and the importance of the patient-physician relationship. The author notes that there are several pathophysiologic alterations found in the small bowel and colon of patients with IBS that could be aggravated or brought to the level of clinical awareness by IBD or its treatment. These alterations include pain or diarrhea after ileo-right colon resection (removal); active proctosigmoiditis; ileal pouch procedures; and an exaggeration of the patient's response to secretagogues, including caffeine and problems with lactose intolerance. The author emphasizes the benefits of explaining to the patient with both IBS and IBD the fact that she or he has two different disorders and that each may cause its own symptoms. Explaining the pathophysiology seems to help the patient adjust medications and understand and accept symptoms caused by meals or by stress. 6 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to irritable bowel syndrome 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:12 •

1998-1999 Complete Directory for People with Rare Disorders Source: Lakeville, CT: Grey House Publishing, Inc. 1998. 726 p. Contact: Available from Grey House Publishing, Inc. Pocket Knife Square, Lakeville, CT 06039. (860) 435-0868. Fax (860) 435-0867. PRICE: $190.00. ISBN: 0939300982. Summary: This directory, from the National Organization for Rare Disorders (NORD) provides a wealth of information on diseases and organizations. The directory offers four sections: disease descriptions, disease specific organizations, umbrella organizations, and government agencies. In the first section, the directory includes descriptions of 1,102 rare diseases in alphabetical order. Each entry defines the disorder, then refers readers to the organizations that might be of interest. Diseases related to digestive diseases include achalasia, Addison's disease, Alagille syndrome, Barrett's esophagus, Budd Chiari syndrome, Caroli disease, celiac sprue, cholangitis, cholecystitis, cirrhosis, colitis, Crohn's disease, Cushing syndrome, cystic fibrosis, diverticulitis, Dubin Johnson syndrome, fructose intolerance, galactosemia, gastritis, gastroesophageal reflux, hepatitis, Hirschprung's disease, Hurler syndrome, imperforate anus, irritable bowel syndrome, jejunal atresia, Korsakoff's syndrome, lipodystrophy, maple syrup urine disease, Morquio syndrome, polyposis, porphyria, proctitis, prune belly syndrome, sarcoidosis, Stevens Johnson syndrome, Tropical sprue, tyrosinemia, valinemia, vitamin E deficiency, Whipple's disease, Wilson's disease, and Zollinger Ellison syndrome. Each of the 445 organizations listed in the second section is associated with a specific disease or group of diseases. In addition to contact information, there is a descriptive paragraph about the organization and its primary goals and program activities. Entries include materials published by the organization as well as the diseases the organizations cover, which refer readers to Section I. The third section lists 444

12

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

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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 key word index concludes the volume.

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CHAPTER 8. SYNDROME

MULTIMEDIA

ON

IRRITABLE

BOWEL

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

Irritable Bowel Syndrome: Tranforming Your Life Through IBS Management Source: Bethesda, MD: Foundation for Digestive Health and Nutrition. 2001. (videocassette). Contact: Available from Foundation for Digestive Health and Nutrition. 7910 Woodmont Avenue, Suite 610, Bethesda, MD 20814-3015. (301) 222-4002. Fax (301) 2224010. E-mail: [email protected]. Website: www.fdhn.org. PRICE: Single copy free to patients. Summary: More than 25 million Americans have irritable bowel syndrome (IBS), some undiagnosed. Yet many are learning how lifestyle and dietary modifications, reduced stress, and appropriate medication can help manage this sometimes debilitating condition. This patient education videotape offers personal stories from IBS patients and guidance from renowned gastroenterologists. Three leading experts explain this

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common, sometimes debilitating, condition and describe how increased understanding in the medical community and better treatments are transforming the lives of people with IBS. Eight patients then share their personal stories about the challenges of living with IBS and how their lives have improved through education and partnerships with their health care providers. The video includes the contact information for the Foundation for Digestive Health and Nutrition (www.fdhn.org) and the American Gastroenterological Association (www.gastro.org), for viewers wanting more information about IBS. •

Biopsychosocial Approach to Irritable Bowel Syndrome: Improving the PhysicianPatient Relationship Source: Milwaukee, WI: International Foundation on Functional Gastrointestinal Disorders. 1997. (videocassette). Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: $100.00 plus $5.00 shipping. Summary: The irritable bowel syndrome (IBS) is a familiar medical disorder characterized by symptoms of abdominal pain and disturbed defecation (diarrhea or constipation). However, management of patients with IBS has been complicated by a lack of precise definition of the syndrome, incomplete and conflicting views of its pathophysiology, and an absence of specific treatments. This continuing education program helps general or family physicians and gastroenterologists to understand the physiological basis for symptom generation in IBS; to improve diagnostic precision through the use of symptom-based criteria, as well as knowledge of the primary symptom type and the severity of the condition; to understand the illness experience and the patient's clinical outcome; and to plan an approach to treatment that incorporates management of both the biological and psychosocial contributions to this disorder. The videotape program and study guide are divided into two sections. The first section reviews the current pathophysiologic understanding of IBS and presents a biopsychosocial approach to diagnosis and treatment. The second section addresses the process of interaction with the patient, and the development of an effective physicianpatient relationship. 103 references. (AA-M).

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What You Really Need to Know About Irritable Bowel Syndrome (IBS) Source: [Toronto, Ontario, Canada]: Videos for Patients. 1994. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $99.00 (Canadian); contact producer for current price in American dollars. Order Number VFP025. Summary: This patient education videotape provides information about irritable bowel syndrome (IBS). The videotape begins with a brief sketch featuring comedian John Cleese and narrator Dr. Robert Buckman illustrating the difficulties sometimes experienced by patients during the traditional doctor's explanation. Topics include a definition of IBS; the symptoms of IBS; diagnostic considerations; treatment options, including changes in diet and lifestyle; and where to get more information and help. Dr. Buckman presents the medical facts, using models, simple diagrams, and graphics to supplement his explanation, and avoiding medical jargon as much as possible.

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Bibliography: Multimedia on Irritable Bowel Syndrome 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 irritable bowel syndrome (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 irritable bowel syndrome: •

Digestive disorders and irritable bowel syndrome [videorecording] Source: a presentation of Films for the Humanities & Sciences; Year: 1993; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1993

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Irritable bowel syndrome [electronic resource]. Year: 2003; Format: Electronic resource; Bethesda, MD: American Gastroenterlogical Association, 2003

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Irritable bowel syndrome [slide] Source: [authors, Douglas A. Drossman, Mark A. Peppercorn, Joseph G. Sweeting]; Year: 1997; Format: Slide; [United States]: American Gastroenterological Association, c1997

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Irritable bowel syndrome [slide] Source: Glaxo Pharmaceuticals; Year: 1992; Format: Slide; New York, NY: HP Pub. Co., 1992

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Irritable bowel syndrome [sound recording]: recorded at DDW 1995 in San Diego Source: AGA; Year: 1995; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, [1995?]

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Irritable bowel syndrome [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital [and] Marshfield Medical Research Foundation; Year: 1990; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1990]

•

Irritable bowel syndrome [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1984; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, [1984]

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Irritable bowel syndrome [videorecording]: diagnosis and clinical management Source: with Douglas A. Drossman; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986

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CHAPTER 9. PERIODICALS AND NEWS ON IRRITABLE BOWEL SYNDROME Overview In this chapter, we suggest a number of news sources and present various periodicals that cover irritable bowel syndrome.

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

M. avium implicated in Crohn's disease, perhaps also irritable bowel syndrome Source: Reuters Medical News Date: August 06, 2003

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•

New drug approach to irritable bowel syndrome Source: Reuters Health eLine Date: May 29, 2003

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Levels of 5-hydroxytryptamine increase after meals in women with irritable bowel syndrome Source: Reuters Medical News Date: May 05, 2003

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Hypnosis improves long-term outcomes in functional dyspepsia Source: Reuters Medical News Date: December 24, 2002

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Irritable bowel syndrome entails economic burden; exercise helps health outlook Source: Reuters Medical News Date: October 21, 2002

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US approves drug for irritable bowel syndrome Source: Reuters Health eLine Date: July 25, 2002

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Zelnorm approved by US FDA for irritable bowel syndrome in women Source: Reuters Medical News Date: July 24, 2002

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Hypnotherapy good for irritable bowel syndrome Source: Reuters Health eLine Date: May 13, 2002

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Menstruation may worsen irritable bowel syndrome Source: Reuters Health eLine Date: March 14, 2002

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Irritable bowel syndrome influenced by environment as well as heredity Source: Reuters Medical News Date: October 30, 2001

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Family setting influences irritable bowel syndrome Source: Reuters Health eLine Date: September 24, 2001

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Corticosteroids may protect against asthma-related irritable bowel syndrome Source: Reuters Medical News Date: August 29, 2001

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Alosetron helpful in subset of women with irritable bowel syndrome Source: Reuters Medical News Date: July 24, 2001

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High rates of irritable bowel syndrome reported in Hong Kong Source: Reuters Medical News Date: December 13, 2000

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Bowel gas volume useful in diagnosing irritable bowel syndrome Source: Reuters Medical News Date: August 09, 2000

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Emotions may affect irritable bowel syndrome Source: Reuters Health eLine Date: July 11, 2000

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Emotional factors may affect irritable bowel syndrome and vice versa Source: Reuters Medical News Date: July 06, 2000

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FDA panel backs drug for irritable bowel syndrome Source: Reuters Health eLine Date: June 27, 2000

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Poor sleep exacerbates symptoms in women with irritable bowel syndrome Source: Reuters Medical News Date: May 30, 2000

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Behavioral therapy improves management of irritable bowel syndrome Source: Reuters Medical News Date: May 01, 2000

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Alosetron relieves symptoms of irritable bowel syndrome in women Source: Reuters Medical News Date: March 27, 2000

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FDA approves drug for irritable bowel syndrome Source: Reuters Health eLine Date: February 10, 2000

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FDA advisers urge approval of new drug for irritable bowel syndrome Source: Reuters Medical News Date: November 17, 1999

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Experimental drug relieves irritable bowel syndrome in women Source: Reuters Medical News Date: November 09, 1999

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Investigational agent tegaserod improves quality of life in irritable bowel syndrome Source: Reuters Medical News Date: October 26, 1999

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Rectal pain threshold lowered in patients with irritable bowel syndrome Source: Reuters Medical News Date: March 22, 1999

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Bacterial gastroenteritis linked to increased risk of irritable bowel syndrome Source: Reuters Medical News Date: February 26, 1999

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Psychological factors may contribute to etiology of irritable bowel syndrome Source: Reuters Medical News Date: February 23, 1999

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Chinese remedies effective for breech birth, irritable bowel syndrome Source: Reuters Medical News Date: November 11, 1998

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Irritable bowel syndrome linked to abnormal colonic fermentation Source: Reuters Medical News Date: October 09, 1998

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Irritable Bowel Syndrome Not Linked Directly To Childhood Abuse Source: Reuters Medical News Date: January 29, 1998

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Irritable Bowel Syndrome Should Not Be Equated With Hypochondriasis Source: Reuters Medical News Date: December 08, 1997

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Chronic Diarrhea In Gulf War Veterans Resembles Symptoms Of Irritable Bowel Syndrome Source: Reuters Medical News Date: May 08, 1996 The NIH

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

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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 “irritable bowel syndrome” (or synonyms).

Newsletters on Irritable Bowel Syndrome Find newsletters on irritable bowel syndrome using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “irritable bowel syndrome.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “irritable bowel syndrome” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

New Testing Techniques for Irritable Bowel Syndrome Source: Newsletter for People with Lactose Intolerance and Milk Allergy. p. 3-4. Spring 1993. Contact: Available from Newsletter for People with Lactose Intolerance and Milk Allergy. P.O. Box 3129, Ann Arbor, MI 48106-3129.\ (313) 572-9134. Summary: This brief article, from a newsletter for people with lactose intolerance and milk allergy, reports on new testing techniques available for irritable bowel syndrome (IBS). Topics include the various etiologic agents possibly responsible for IBS; the traditional diagnostic methods used to confirm IBS; and the new test, called a bowel scintiscan, that reveals gaps in the emptying process of the large intestine. These gaps indicate areas of the bowel that function abnormally, therefore demonstrating the presence of IBS. The article notes that the test is still experimental and is only available through the Mayo Clinic in Rochester, Minnesota.

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 “irritable bowel syndrome” (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 irritable bowel syndrome: •

Irritable Bowel Syndrome: Clinical Issues Source: Participate. 9(1): 1-4. Spring 2000. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org.

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Summary: This article discusses irritable bowel syndrome (IBS), a very common condition that is characterized by abdominal pain associated with a change in a bowel pattern (constipation or diarrhea). IBS is considered a condition of the brain-gut connection and triggering factors may variously cause symptoms of diarrhea at one time and constipation at another. There is a wide range of severity of IBS, from mild or infrequent symptoms that the patient manages at home to very severe kinds of symptoms that can cause patients to seek relief with more frequent doctor visits. The article answers common questions about IBS and its treatments. IBS is in the group of conditions that are called functional gastrointestinal disorders, i.e., disorders of dysfunction, rather than pathology such as inflammation or visible tissue damage. Diagnosis include patient history, symptoms according to the Rome Criteria, and diagnostic tests such as colonoscopy or CT scan (computed tomography). Treatments are usually done in response to the specific symptoms. For example, in a patient who usually has constipation, treatment are used that increase the functioning of the bowel, the frequency, and the ease of having a bowel movement. For patients whose symptoms tend more to diarrhea, treatment includes anti diarrheal agents. Pain medications might also be indicated, particularly if the pain is meal related. Reduced dosage prescriptions of antidepressants can be effective to modulate or decrease pain. The author reviews new drugs currently under study, as well as ongoing research into the brain-gut connection. The author also discusses the impact of conceptualizing functional disorders within the traditional disease-based medical framework, which separates the mind from the body. IBS must be recognized as genuine, non trivial, and a disorder that is not fully explained as either psychiatric or organic. •

Irritable Bowel Syndrome: The Bottom Line Source: Fibromyalgia Frontiers. 7(2): 4-8, 13. March-April 1999. Contact: Available from Fibromyalgia Association of Greater Washington, Inc. 13203 Valley Drive, Woodbridge, VA 22191-1531. (703) 790-2324. Fax (703) 494-4103. E-mail: [email protected]. Summary: This article on irritable bowel syndrome (IBS) is from a newsletter for people with fibromyalgia (a pain disorder). IBS is known as a functional gastrointestinal (GI) disorder because it involves a healthy bowel, without inflammation or disease, that does not perform normally. In IBS, the bowel tends to have an unusual sensitivity to such events as the passage of food particles, fluids, or gas. IBS symptoms, which are usually intermittent rather than constant, are abdominal discomfort, cramping or pain, bloating, abnormal bowel movements (i.e., diarrhea, constipation, or the two alternating), mucus in the stools, and a sensation of incomplete evacuation. IBS is quite common among persons with fibromyalgia; its incidence is estimated at approximately 40 percent among patients with diagnosed fibromyalgia (compared with only 16 percent in normal controls). However, some GI signs are not part of IBS and should be investigated. The author then discusses the pathophysiology of IBS and the treatment options for the syndrome. Although admittedly not high tech, modifying the diet and eating habits and learning to control stress are the most potent weapons available against IBS. Dietary fiber has a central role, and it is important to increase one's intake of fiber slowly to allow the body to adjust and to drink plenty of water as fiber intake increases. The article concludes with the contact information for the International Foundation for Functional Gastrointestinal Disorders and for the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. 18 references.

Periodicals and News

•

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Irritable Bowel Syndrome: Gaining Control of Your Symptoms Source: Mayo Clinic Health Letter. 17(2): 4-5. February 1999. Contact: Available from Mayo Foundation for Medical Education and Research. 200 First Street, SW, Rochester, MN 55905. Summary: This newsletter article offers strategies to help people with irritable bowel syndrome (IBS) gain control of their symptoms. IBS is a common, chronic gastrointestinal disorder in which the structure of the bowel is normal, but the function is not. The symptoms are produced, in part, by spasms in the walls of the intestines. Some people mainly experience cramping and diarrhea, others alternate between constipation and diarrhea, or have predominantly pain and constipation. Bloating and gas are also common. IBS can be difficult to diagnose because many conditions have similar symptoms. Common treatments include dietary changes, managing stress, the use of medications, antidepressants, and alternative therapies, such as peppermint oil. A sidebar addresses the issue of a psychological basis for IBS, concluding that stress no doubt aggravates IBS, but that one doesn't have to be under stress to have the condition. 1 figure.

•

Current Approach to the Diagnosis of Irritable Bowel Syndrome Source: Participate. 10(1): 1-3. Spring 2001. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. Summary: This newsletter article reviews the current approach to the diagnosis of irritable bowel syndrome (IBS). Physicians now rely less on extensive testing to exclude other disorders and instead can diagnose IBS in most patients by recognizing certain symptom details, performing a physical examination, and undertaking limited diagnostic testing. Extensive testing is usually reserved for special situations. Various symptom criteria have been proposed; the Rome II criteria are presently in use. Rome II criteria for IBS are symptoms at least 12 weeks or more in duration, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has two out of three features: relieved with defecation, onset associated with a change in frequency of stool, or onset associated with a change in form (appearance) of stool. Other symptoms that are not essential but that support the diagnosis of IBS include abnormal stool frequency (greater than 3 bowel movements per day or less than 3 bowel movements per week), abnormal stool form, abnormal stool passage, passage of mucus, or bloating or feeling of abdominal distension. The discomfort or pain and abnormal bowel habit of IBS typically fluctuate in severity, may be associated with stressful life events, and occur over a long time period. Diagnostic tests can include blood tests, stool tests, sigmoidoscopy or colonoscopy, barium enema, and psychological tests. Diagnosis by careful review of the patient's symptoms, a physical examination, and selected diagnostic procedures is quite secure, as followup for many years of confidently diagnosed patients seldom disclose another cause for their symptoms. With an unequivocal diagnosis, both patient and physician can work together on the most effective management.

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

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

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for irritable bowel syndrome. 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 irritable bowel syndrome. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks,

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etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to irritable bowel syndrome: Alosetron •

Systemic - U.S. Brands: Lotronex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500107.html

Antacids •

Oral - U.S. Brands: Advanced Formula Di-Gel; Alamag; Alamag Plus; Alenic Alka; Alenic Alka Extra Strength; Alka-Mints; Alkets; Alkets Extra Strength; Almacone; Almacone II; AlternaGEL; Alu-Cap; Aludrox; Alu-Tab; Amitone; Amphojel; Antacid Gelcaps; Antacid Liquid; Antacid L http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202047.html

Fluoxetine •

Systemic - U.S. Brands: Prozac; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202247.html

Loperamide •

Oral - U.S. Brands: Imodium http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202332.html

Simethicone •

Oral - U.S. Brands: Flatulex; Gas-X; Genasyme; Phazyme; Phazymehttp://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202522.html

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

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

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

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APPENDICES

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

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

•

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

•

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

•

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

•

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

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

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

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

13

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

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

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

•

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

•

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

•

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

•

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

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

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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/

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

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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

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

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

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “irritable bowel syndrome” 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 “irritable bowel syndrome” (or synonyms) into the “For these words:” box. The following is a sample result: •

Irritable Bowel Syndrome: New Findings and Treatments: Special Report Source: New York, NY: McMahon Publishing Group. 2000. 8 p. Contact: Available from Gastroenterology and Endoscopy News. McMahon Publishing Group, 545 W. 45th St., 8th floor, New York, NY 10036. (800) 526-0828. Website: www.mcmahonmed.com. PRICE: $5.00 plus shipping and handling. Summary: This report offers a continuing education activity for physicians who see patients with irritable bowel syndrome (IBS). The authors outline the characteristics and presenting symptoms of various patient subtypes and report on recent findings indicating the central role of serotonin in the pathophysiology of IBS, as well as new pharmacotherapeutic agents (drug therapy) developed for IBS. Approximately 95 percent of all serotonin (5HT) is located in the gastrointestinal (GI) tract; the remainder is located in the central nervous system. The abundance of 5HT in the GI tract indicates that this neurotransmitter plays a major role in GI function. 5HT modulates motility (movement through the GI tract), visceral perception (feelings, such as pain, arising from the gut), and intraluminal secretion; these are all roles that have been linked to the pathophysiology of IBS. Until recently, no pharmaceutical agents have been developed specifically for IBS. The ability of 5HT2 and 5HT4 agents to reduce the multiple symptoms associated with IBS provides not only direct relief but indirect relief as well, and confirms the neurobiologic basis of this GI disorder of function. Specific drugs discussed include alosetron (a 5HT2 antagonist), tegaserod (a 5HT4 agonist), and prucalopride (a 5HT4 agaonist). A posttest is appended, with which readers can qualify for continuing education credits. References are provided in the text of the report. 4 figures. 1 table.

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine 16

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

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(NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “irritable bowel syndrome” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 5 40 886 4 0 935

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “irritable bowel syndrome” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or

17

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). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19

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

20

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 21 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 22 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story.

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more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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/.

23

After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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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 irritable bowel syndrome 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 irritable bowel syndrome. 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 irritable bowel syndrome. 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 “irritable bowel syndrome”:

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•

Guides on irritable bowel syndrome Irritable Bowel Syndrome http://www.nlm.nih.gov/medlineplus/tutorials/irritablebowelsyndromeloader.ht l

•

Other guides Chronic Fatigue Syndrome http://www.nlm.nih.gov/medlineplus/chronicfatiguesyndrome.html Colonic Diseases http://www.nlm.nih.gov/medlineplus/colonicdiseases.html Colorectal Cancer http://www.nlm.nih.gov/medlineplus/colorectalcancer.html Coronary Disease http://www.nlm.nih.gov/medlineplus/coronarydisease.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Dietary Fiber http://www.nlm.nih.gov/medlineplus/dietaryfiber.html Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseases.html Diverticulosis and Diverticulitis http://www.nlm.nih.gov/medlineplus/diverticulosisanddiverticulitis.html Irritable Bowel Syndrome http://www.nlm.nih.gov/medlineplus/irritablebowelsyndrome.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Mental Health http://www.nlm.nih.gov/medlineplus/mentalhealth.html Panic Disorder http://www.nlm.nih.gov/medlineplus/panicdisorder.html Post-Traumatic Stress Disorder http://www.nlm.nih.gov/medlineplus/posttraumaticstressdisorder.html Preventing Disease and Staying Healthy http://www.nlm.nih.gov/medlineplus/preventingdiseaseandstayinghealthy.html Stomach Disorders http://www.nlm.nih.gov/medlineplus/stomachdisorders.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html Veteran's Health http://www.nlm.nih.gov/medlineplus/veteranshealth.html

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Wilson's Disease http://www.nlm.nih.gov/medlineplus/wilsonsdisease.html

Within the health topic page dedicated to irritable bowel syndrome, the following was listed: •

Diagnosis/Symptoms Abdominal Pain, Chronic: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/528.html Colonoscopy http://www.nlm.nih.gov/medlineplus/tutorials/colonoscopyloader.html Colonoscopy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/colonoscopy/index.htm Radiography-Lower GI Tract (Barium Enema “BE”) Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/lower_gi.htm

•

Nutrition Fiber: How to Increase the Amount in Your Diet Source: American Academy of Family Physicians http://familydoctor.org/handouts/099.html

•

Organizations American Gastroenterological Association http://www.gastro.org/ National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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 irritable bowel syndrome. CHID offers summaries that describe the guidelines available, including contact information and pricing.

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CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Irritable Bowel Syndrome: The Pathophysiological Links to More Effective Future Therapy Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders (IFFGD). 1996. 1 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: Single copy free; bulk copies available. Summary: In this fact sheet, the author explores the pathophysiologic (disease process) links between the brain, motility, and sensation in irritable bowel syndrome (IBS). Current available data suggest that investigators and clinicians need to be dissuaded from approaching IBS as though it was a single disorder in all patients, or as though only one mechanism is responsible for development of symptoms. The author stresses the importance of integrated rather than reductionist approaches to research, diagnosis, and management of IBS. The author concludes that motor and sensory functions in the human bowel are intimately linked to higher and lower centers in the brain.

•

Irritable Bowel Syndrome Research: What Is Being Done Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders (IFFGD). 1996. 2 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: Single copy free; bulk copies available. Summary: In this fact sheet, the author highlights irritable bowel syndrome (IBS) research results that were published or presented in 1995, focusing on those studies with the most clinical relevance. Topics include research defining IBS; the delineation of symptoms; the role of genetics versus environment in the development of IBS; the diagnosis of IBS; treatment options; and cost considerations. The author emphasizes that as consumers of medical information, people with IBS must learn to critically appraise any new information released from research studies.

•

Irritable Bowel Syndrome Source: Emeryville, CA: Parlay International. 1995. [4 p.]. Contact: Available from Parlay International. Box 8817, Emeryville, CA 94662-0817. (800) 457-2752. Website: www.parlay.com. PRICE: $20.00 per package of 50. Order number: 7052. Summary: Irritable bowel syndrome (IBS) is diagnosed when someone suffers from abdominal cramps and changes in bowel habits (diarrhea, constipation, nausea) without signs of serious disease such as fever, weight loss, or bleeding. Before a diagnosis of IBS is made, the symptoms have usually been present for at least 6 months with all diagnostic tests normal. This brochure offers basic information about IBS, noting that it

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is a chronic condition that can be controlled, but is rarely cured. The brochure focuses on the causes of the illness and on strategies for easing the pain. In most cases, people with IBS can alleviate their symptoms by carefully monitoring their diets, managing stress, and maintaining a regular exercise program. The best way to control the associated muscle spasms is to increase the amount of bulk in the intestinal tract by increasing the amount of fiber in the diet. Fiber makes stools bulkier and softer so the colon does not have to work as hard. The increased bulk decreases the intensity and frequency of contractions and promotes a smoother passage through the intestine. The brochure lists specific strategies for increasing fiber in the diet. The brochure also briefly discusses the role of stress in the management of IBS. The brochure is illustrated with full-color photographs. •

What You Can Do About Irritable Bowel Syndrome Source: Cincinnati, OH: Procter and Gamble Company. 1992. 14 p. Contact: Available from Procter and Gamble Company. P.O. Box 86, Cincinnati, OH 45201-0086. (800) 428-8363. PRICE: Single copy free. Summary: This booklet was created to help patients understand irritable bowel syndrome (IBS) and to provide some general guidelines. Written in a question-andanswer format, the booklet includes a definition of IBS and provides information about symptoms; the causes of IBS-related pain; the anatomy of the digestive tract; recommendations for lifestyle changes to ease symptoms; the role of dietary fiber and how to change one's diet to increase the amount of fiber; the amount of fiber in various foods; and the different kinds of fiber. The booklet concludes with a description of the uses of Metamucil, a fiber supplement.

•

Irritable Bowel Syndrome (IBS) Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders. 1998. 8 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: Free for members; $1.00 for nonmembers; plus shipping and handling. Order number: 101IBS. Summary: This brochure describes irritable bowel syndrome (IBS), a disturbance of intestinal function with symptoms of abdominal discomfort, bloating, and abnormal bowel movements. Diarrhea may often alternate with constipation. The typical features of IBS are recognizable to a physician, but need not all be present and may appear with some variation in different patients. The most important step in diagnosis is to rule out other diseases; this is done through a detailed history, physical examination, laboratory tests, x-rays, and endoscopy. Although the cause of IBS is not known, symptoms appear to be the result of increased sensitivity to distension of the gastrointestinal (GI) tract by gas or fecal material and a tendency for the bowel to be overly reactive to almost anything: eating, stress, emotional arousal, or gaseous distension. Lactose (milk sugar) intolerance can have similar symptoms to IBS, and while they can occur at the same time in a patient, they are different problems. The brochure discusses remissions and prognosis, the causes of bloating and gas, colitis and how it differs from IBS, treatment options, the impact of the menstrual cycle on IBS symptoms, and the relationship of stress and IBS. Treatment options discussed include evaluation of stress level and diet, diet therapy (increasing dietary fiber, avoiding laxatives, reducing trigger foods),

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lifestyle changes, drug therapy, biofeedback, and psychological counseling. The brochure summarizes seven strategies for coping with IBS. The brochure includes a brief description of the International Foundation for Functional Gastrointestinal Disorders. 1 figure. •

Guide to Controlling Irritable Bowel Syndrome Source: San Bruno, CA: StayWell Company. 1999. 7 p. Contact: Available from Staywell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $1.25 per copy; plus shipping and handling. Summary: This brochure offers a user friendly approach to understanding and coping with irritable bowel syndrome (IBS). The brochures stresses the importance of consulting a doctor for diagnosis, because symptoms similar to those of IBS can sometimes be caused by other more serious bowel conditions. IBS is the digestive tract's abnormal reaction to the stresses and strains of daily life, as well as to the routine activity of processing food. The brochure reviews normal digestion, including the role of the esophagus, stomach, small intestine, colon, sigmoid colon, and rectum. The symptoms of abdominal pain, constipation, and diarrhea are typical in patients with IBS. With IBS, the natural motility of the bowel muscle is disrupted; motility is the rhythmic wave like motion the bowel makes to move body waste along. Tension, eating, smoking, and alcohol all can alter normal motility. Treatment programs can include medication, changes in the diet, and lifestyle modifications to reduce stress (including exercise, biofeedback meditation, and counseling or support groups). The brochure stresses that continued medical followup is essential to monitor the success of the treatment program. Each concept in the brochure is illustrated with cartoon type line drawings featuring patients and a group of elf characters who are shown as the inner workings of the digestive tract.

•

When Your Doctor Says You Have Irritable Bowel Syndrome Source: Milwaukee, WI: Schwarz Pharma. 1993. 6 p. Contact: Available from Schwarz Pharma. P.O. Box 2038, Milwaukee, WI 53201. (800) 558-5114, (414) 354-4300. PRICE: Free (packs of 50); single copy also available. Order number SP0599B 5/93. Summary: This brochure presents a brief overview for newly-diagnosed patients with irritable bowel syndrome (IBS). Topics include the symptoms of IBS; the normal function of the digestive system; how the digestive system works in IBS; managing IBS; IBS and the diet, including common foods that may aggravate IBS; dietary fiber intake; and drug therapy for IBS. Simple line drawings illustrate some of the concepts presented.

•

IBS: Irritable Bowel Syndrome. Do You Have It? How Serious Is It? How Can You Get Rid of It? Source: Fort Worth, TX: Konsyl Pharmaceuticals, Inc. 1994. 2 p. Contact: Available from Konsyl Pharmaceuticals, Inc. 4200 South Hulen Street, Fort Worth, TX 76109. (800)356-6795 or (817) 763-8011. PRICE: Single copy free. Summary: This brochure provides a general introduction to irritable bowel syndrome (IBS). The brochure reviews primary symptoms, including abdominal pain, diarrhea,

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and constipation; complications; diagnostic tests; the role of lifestyle, including exercise; and the importance of adequate dietary fiber to control symptoms. •

Soothing the Symptoms of Irritable Bowel Syndrome: Recognizing Symptoms, Relieving Discomfort Source: Cincinnati, OH: Procter and Gamble. 1994. 12 p. Contact: Available from Metamucil-Procter and Gamble. P.O. Box 9032, Cincinnati, OH 45209-9970. PRICE: Single copy free; bulk copies available. Summary: This brochure provides a general overview of irritable bowel syndrome (IBS) and gives recommendations on how to manage it. Topics include the typical symptoms of IBS; the physiology of the digestive system; the role of food and stress in IBS; diagnostic tests used to confirm IBS; treatment options, including diet, stress management, and medications; the role of a high fiber diet; and the use of fiber supplements, including the product Metamucil. The brochure is produced by the manufacturer of Metamucil. The brochure includes a reply card to obtain more information about Metamucil products. 4 figures. 1 table.

•

IBS: Irritable Bowel Syndrome Source: Fort Worth, TX: Konsyl Pharmaceuticals, Inc. 1997. [2 p.]. Contact: Available from Konsyl Pharmaceuticals, Inc. 4200 South Hulen Street, Suite 513, Fort Worth, TX 76109-4912. (800) 356-6795 or (817) 763-8011. Fax (817) 731-9389. Website: www.konsyl.com. PRICE: Single copy free. Summary: This brochure provides basic information about irritable bowel syndrome (IBS), a chronic digestive disease characterized by abdominal pain, diarrhea, and constipation. Other common symptoms are indigestion, nausea, gas, and bloating. The symptoms are usually intermingled to varying extents so that all patients' symptoms are relatively unique to them. Although IBS is not life threatening, accurate diagnosis and subsequent treatment are vital. Diagnostic tests, including a full patient history and colonscopy, can determine if there is a structural abnormality or a functional disorder like IBS. The brochure focuses on the use of diet therapy for managing IBS, including the use of increased dietary fiber intake. Fiber is a general term for food which is not absorbed into the system and which stays in the stool, thereby increasing the stool bulk. The author emphasizes the use of fiber supplements, such as Konsyl (the manufacturer of which is the producer of this brochure). One sidebar comments on the impact of the nervous system on the digestive tract. The brochure is illustrated with full color drawings and photographs. 3 figures.

•

Irritable Bowel Syndrome: Questions and Answers Source: Arlington Heights, IL: American Society of Colon and Rectal Surgeons. 1996. 2 p. Contact: Available from American Society of Colon and Rectal Surgeons. 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005. (800) 791-0001 or (847) 2909184. Fax (847) 290-9203. Price: Single copy free; bulk copies available. Summary: This brochure, from the American Society of Colon and Rectal Surgeons, provides basic information about irritable bowel syndrome (IBS). People with IBS may experience constipation, diarrhea, or a combination; in addition, IBS may produce cramps, urgency, or a gassy, bloated feeling in the abdomen. The brochure outlines the

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symptoms of IBS, its causes, and treatment options. The underlying cause of this disorder is an abnormality in the way the intestinal muscles contract. The brochure notes that emotional stress may contribute to IBS. The brochure stresses that a careful medical history and physical examination are essential to a proper diagnosis. Tests performed to confirm IBS may include flexible sigmoidoscopy, colonoscopy, hemoocult testing to detect hidden blood in the stool, xray examination of the lower intestines, and a psychological evaluation. Therapeutic options include lowering stress levels, increasing fiber in the diet, avoiding certain foods including caffeine, milk products or alcohol, and quitting smoking. The brochure emphasizes that achieving relief of IBS symptoms is often a slow process. 1 figures. (AA-M). •

Irritable Colon Syndrome Source: in Sodeman, W.A., Jr. Instructions for Geriatric Patients. Philadelphia, PA: W.B. Saunders Company. 1995. p. 120-121. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $38.95. ISBN: 0721643353. Summary: This chapter, from a book of instructions for geriatric patients, provides a basic information sheet on irritable colon syndrome or irritable bowel syndrome (IBS). IBS can affect persons of any age. Patients commonly experience long periods that are free of symptoms, punctuated by attacks of the problem that may last for days, weeks, or occasionally months. While stress seems to initiate the attack, the author emphasizes that it is does not so much cause the underlying problem as make it slightly worse so that it becomes apparent. IBS presents as a change in bowel habit, most often diarrhea. Treatment involves using medications to attempt to normalize the digestive tract function. Addition of a fiber supplement to the diet often benefits patients with IBS. The information sheet concludes by reminding readers to contact their health care provider if they have any change in their bowel habits. The instructions are designed to supplement and reinforce physician instructions to their patients. (AA-M).

•

Functional Dyspepsia and IBS: Incidence and Characteristics Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders. 1997. 1 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: $0.50. Summary: This fact sheet describes and compares the incidence and characteristics of functional dyspepsia and irritable bowel syndrome (IBS). Functional dyspepsia is characterized by chronic or recurrent pain or discomfort centered in the upper abdomen, with no evidence of organic disease or structural or biochemical abnormality. The authors describe three types of functional dyspepsia: ulcer-like, dysmotility like, and unspecified. Dyspepsia occurs in about 30 percent of adults; about half that many have functional dyspepsia. Functional dyspepsia can be treated with changes in diet or with medications. IBS is a functional bowel disorder that can include chronic symptoms of abdominal pain, constipation, bloating of the abdomen, and diarrhea. IBS is very common, appearing in as many as 15 to 20 percent of people in Western countries. Education and changes in diet and lifestyle are often effective in managing relatively mild symptoms. A first step toward individual diet modification is to identify and avoid

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foods that make symptoms worse. Medications may be helpful for those with more severe symptoms. (AA-M). •

Gynecological Aspects of Irritable Bowel Syndrome Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders. 1996. 1 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: $0.50. Summary: This fact sheet focuses on the gynecological and bladder aspects of irritable bowel syndrome (IBS) in women. The author reports on research that found women with IBS tended to suffer more from painful periods (menstruation), noticed that their IBS symptoms were worse at the time of their periods, and frequently experienced pain during or after sexual intercourse. The sexual pain resembled bowel pain and often came on some time after intercourse, sometimes as late as the next day. The author encourages patients and their partners to become educated about this aspect of IBS in order to reduce stress on the patient. The author discusses the differential diagnosis of IBS from a gynecological perspective, including pelvic inflammatory disease (PID), endometriosis, and gynecological cancer. The author calls for greater collaboration between gastroenterologists and gynecologists when treating patients with lower abdominal pain. The fact sheet also briefly describes the bladder symptoms that are most often seen in patients with IBS. These symptoms include frequency in passing urine, urgency, and sometimes a degree of incontinence. The author cautions that treating supposed urinary tract infections with antibiotics can make the IBS worse and recommends only treating cystitis when it is proven on urine culture. The author concludes by encouraging readers to educate themselves about the possible nongastrointestinal aspects of IBS and to proceed very cautiously when offered surgical answers to their problems. (AA-M).

•

Irritable Bowel Syndrome (Spastic Colon; Colitis) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 255. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This fact sheet provides basic information on frequent signs and symptoms, causes, risk factors, preventive measures, etc.; treatment, medication, and diet; and when to contact one's health care provider. The fact sheet is designed to be photocopied and distributed to patients as a reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish.

•

Gut Motility: In Health and Irritable Bowel Syndrome Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders (IFFGD). 1995. 2 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: Single copy free to members; $1.00 for nonmembers.

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Summary: This newsletter article describes gut motility in both normal health and in irritable bowel syndrome. Gut motility is defined as the stretching and contractions of the muscle in the wall of the stomach and bowel. These movements enable the food to progress along the digestive tract while at the same time ensuring the absorption of the important nutrients. Topics include the normal movements of the digestive tract, diagnostic tests that measure these movements of the gut, the types of contraction in the gut, motility in the stomach, small bowel and large bowel (colon), the production of intestinal gas, disorders affecting the motility of the digestive tract, irritable bowel syndrome (IBS), the causes of IBS (including trigger factors), the complications associated with uncoordinated or abnormally high pressure contractions, impairment of propulsive activity, excessive numbers of contractions, delayed or accelerated transit through the intestines, the role of mental stress in IBS symptoms, and the different methods of treating the symptoms of IBS. •

Taking Care of Irritable Bowel Syndrome Source: Santa Cruz, CA: ETR Associates. 1997. 4 p. Contact: Available from ETR Associates. 4 Carbonero Way, Scotts Valley, CA 950664200. (800) 321-4407. Fax (800) 435-8433. Website: www.etr.org. PRICE: Single copy free; $16.00 for 50 copies, discounts for larger orders. Order number: 004. Summary: This patient education brochure explains the basics of living with irritable bowel syndrome (IBS). The brochure encourages readers to check with their health care provider for assistance in dealing with the discomfort and inconvenience of recurrent and chronic cramps, gas, bloating, diarrhea, or constipation. The brochure discusses causes of IBS, the physiology of normal digestion, how to discover individual triggers of symptoms, common dietary triggers of IBS symptoms (caffeine; dairy products; chocolate; alcohol; and acidic, fatty, or spicy foods), how to manage symptoms, the role of medications, and how to learn to manage stress (a common trigger of IBS symptoms). The brochure emphasizes the role of exercise and nutrition in managing IBS. The brochure also lists symptoms for which a health care provider should be consulted, including blood in the stool, continuous abdominal pain and fever, and when symptoms interfere with normal activities. The brochure concludes with a brief list of references and the contact information for the National Digestive Diseases Information Clearinghouse. 1 figure. 3 references. (AA-M).

•

Irritable Bowel Syndrome: Tips on Controlling Your Symptoms Source: Kansas City, MO: American Academy of Family Physicians. 2001. 4 p. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. PRICE: $12.50 for 50 copies for members, $18.75 for 50 copies for nonmembers. Order number: 1521. Summary: This patient education brochure helps readers understand irritable bowel syndrome (IBS) and how they can control the symptoms it may cause. In IBS, the intestines squeeze too hard or not hard enough and cause food to move too fast or too slowly through the gastrointestinal (GI) tract. IBS can cause diarrhea, constipation, or both. The symptoms may get worse when the patient experiences stress, including that associated with travel, social events, menstrual cycles, or a change in daily routine. The brochure outlines diagnostic and treatment options, the role of dietary fiber, the impact of diet on IBS symptoms, the role of milk and milk products and the issue of lactose intolerance, managing stress, and drug therapy. The brochure notes that because IBS is a

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chronic disease, health care providers are hesitant to prescribe long term drug therapy. However, for acute attacks, antispasmodic drugs, loperamide, sedatives, or antidepressants may be prescribed. The brochure encourages readers to find new freedom from IBS by following a management plan that includes a healthy diet, learning new ways to deal with stress, and avoiding foods that make symptoms worse. 2 tables. (AA-M). •

Understanding: Irritable Bowel Syndrome Source: Pittsburgh, PA: SmithKline Beecham Consumer Brands. 2003. 4 p. Contact: Available from SmithKline Beecham. Consumer Brands, P.O. Box 1467, Pittsburgh, PA 15230. (800) 245-1040. PRICE: Single copy free. Bulk orders available to physicians by calling (800) 233-2426. Summary: This patient education brochure provides basic information about irritable bowel syndrome (IBS). Topics include a description of IBS; causes; symptoms; treatment, including stress management, diet therapy, and the role of fiber. The brochure concludes with a section about fiber. The brochure, produced by the manufacturers of CITRUCEL, a fiber product, describes the use of CITRUCEL as part of a therapeutic program to manage IBS. 4 references.

•

Irritable Bowel Syndrome: What It Is and What to Do About It Source: American Family Physician. 53(4): 1241-1242. March 1996. Summary: This patient education handout from American Family Physician magazine familiarizes readers with irritable bowel syndrome (IBS) and how to manage it. Written in a question and answer format, the handout covers a definition of IBS, its symptoms, treatment options, dietary changes that may relieve symptoms, medications that can be used to treat acute episodes, and dealing with stress that may cause or exacerbate symptoms. The handout encourages people with IBS to take an active role in the management of the disease. The National Guideline Clearinghouse™

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

American Gastroenterological Association medical position statement: irritable bowel syndrome Source: American Gastroenterological Association - Medical Specialty Society; 1996 November 10 (revised 2002 Dec); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3685&nbr=2911&a mp;string=mucous+AND+colitis 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

234 Irritable Bowel Syndrome

located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

About Irritable Bowel Syndrome Summary: Irritable bowel syndrome is the most common disease diagnosed by gastroenterologists (doctors who specialize in medical treatment of disorders of the stomach and intestines) and one of the most common Source: International Foundation for Functional Gastrointestinal Disorders http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7668

•

Irritable Bowel Syndrome Summary: Irritable bowel syndrome (IBS) is a common disorder of the intestines that leads to crampy pain, gassiness, bloating, and changes in bowel habits. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=737

•

Irritable Bowel Syndrome in Children Summary: Irritable bowel syndrome (IBS) is a digestive disorder that causes abdominal pain, bloating, gas, diarrhea, and constipation--or some combination of these problems. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6514

•

Lotronex Information Summary: This page presents information for women using the prescription drug Lotronex (alosetron hydrochloride) for treatment of the diarrhea-predominant form of irritable bowel syndrome (IBS). Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5504

•

What I Need to Know About Irritable Bowel Syndrome Summary: This fact sheet describes irritable bowel syndrome (IBS) and its causes, symptoms, diagnosis, tests, and treatment. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6549 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

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ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to irritable bowel syndrome. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “irritable bowel syndrome” (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 “irritable bowel syndrome”. 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 “irritable bowel syndrome” (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 “irritable bowel syndrome” (or a synonym) into the search box, and click “Submit Query.”

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.24

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

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

24

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)25: •

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

•

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/

25

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

240 Irritable Bowel Syndrome

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

242 Irritable Bowel Syndrome

•

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

243

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 irritable bowel syndrome: •

Basic Guidelines for Irritable Bowel Syndrome Giardia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000288.htm Irritable bowel syndrome (functional bowel) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000246.htm

•

Signs & Symptoms for Irritable Bowel Syndrome Abdominal distention Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003122.htm Abdominal fullness, gaseous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003124.htm Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm

244 Irritable Bowel Syndrome

Abdominal tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Bloating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003123.htm Constipation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003125.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Irritable Bowel Syndrome ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm Barium enema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003817.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Differential Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm ESR Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Sigmoidoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003885.htm

Online Glossaries 245

•

Nutrition for Irritable Bowel Syndrome Caffeine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002445.htm Fiber Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002470.htm

•

Background Topics for Irritable Bowel Syndrome Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Relieved by Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002288.htm Stimulants Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002308.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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IRRITABLE BOWEL SYNDROME DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal 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] Absenteeism: Chronic absence from work or other duty. [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] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [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] 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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [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]

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Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aerophagia: A condition that occurs when a person swallows too much air. Causes gas and frequent belching. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] 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] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever;

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fits may be provoked by substances in the working environment. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Aloe: A genus of the family Liliaceae containing anthraquinone glycosides such as aloinemodin or aloe-emodin (emodin). [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH]

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Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [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] Anterograde: Moving or extending forward; called also antegrade. [EU] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic

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treatment of anxiety but are not included here. [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]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antiproliferative: Counteracting a process of proliferation. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also

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neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antispasmodic: An agent that relieves spasm. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apnea: A transient absence of spontaneous respiration. [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] Appendectomy: An operation to remove the appendix. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aptitude: The ability to acquire general or special types of knowledge or skill. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arrhythmogenic: Producing or promoting arrhythmia. [EU] 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]

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Arthralgia: Pain in the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [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] Autonomic Pathways: Nerves and plexuses of the autonomic nervous system. The central nervous system structures which regulate the autonomic nervous system are not included. [NIH]

Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH]

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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] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium enema: A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Belching: Noisy release of gas from the stomach through the mouth. Also called burping. [NIH]

Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [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

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diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological 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] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH]

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Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood 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 Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Body Regions: Anatomical areas of the body. [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] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [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] Bromelain: An enzyme found in pineapples that breaks down other proteins, such as collagen and muscle fiber, and has anti-inflammatory properties. It is used as a meat tenderizer in the food industry. [NIH] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] 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]

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Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bulking Agents: Laxatives that make bowel movements soft and easy to pass. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] 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 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] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [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] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH]

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Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catalyse: To speed up a chemical reaction. [EU] 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] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH]

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Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell 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] 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] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [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] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial)

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bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholelithiasis: Presence or formation of gallstones. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [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] 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 Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [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] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2

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receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Claudication: Limping or lameness. [EU] 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] Clitoral: Pertaining to the clitoris. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant

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behavior. [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] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols 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,

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IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] 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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH]

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Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constrict: Tighten; narrow. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continence: The ability to hold in a bowel movement or urine. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [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] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [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] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right

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atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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 Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [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] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] 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] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to

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which a subject has learned to respond. [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] Cystitis: Inflammation of the urinary bladder. [EU] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] 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] 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] Defecation: The normal process of elimination of fecal material from the rectum. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deglutition: The process or the act of swallowing. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by

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rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Descending Colon: The part of the colon where stool is stored. Located on the left side of the abdomen. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH]

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Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Devazepide: A derivative of benzodiazepine that acts on the cholecystokinin A (CCKA) receptor to antagonize CCK-8's (sincalide) physiological and behavioral effects, such as pancreatic stimulation and inhibition of feeding. [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] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [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] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphenoxylate: A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense

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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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] 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] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diurnal: Occurring during the day. [EU] Diverticula: Plural form of diverticulum. [NIH] Diverticulitis: Inflammation of a diverticulum or diverticula. [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] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [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] 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] 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

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before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]

symptoms

resulting

from

an

absent

or

Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [NIH] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]

Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysmenorrhoea: Painful menstruation. [EU] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysphoria: Disquiet; restlessness; malaise. [EU] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dysuria: Painful or difficult urination. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] 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

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commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emetic: An agent that causes vomiting. [EU] 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] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] 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] 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]

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Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] 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, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] 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] Enema: The injection of a liquid through the anus into the large bowel. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or

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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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Achalasia: Disorder of lower esophagogastric motility due to failure of the lower esophageal sphincter to relax with swallowing. It is sometimes caused by degeneration of the ganglion cells of the myenteric plexus or of the vagal motor nuclei. [NIH]

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Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] 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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [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] Extrapyramidal: Outside of the pyramidal tracts. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [NIH] Febrile: Pertaining to or characterized by fever. [EU]

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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] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flatus: Gas passed through the rectum. [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] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Hypersensitivity: Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens ingested in food. [NIH] Forearm: The part between the elbow and the wrist. [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

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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]

Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [NIH] Freeze-dried: A method used to dry substances, such as food, to make them last longer. The substance is frozen and then dried in a vacuum. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fructose Intolerance: An autosomal recessive fructose metabolism disorder due to deficient fructose-1-phosphate aldolase (EC 2.1.2.13) activity, resulting in accumulation of fructose-1phosphate. The accumulated fructose-1-phosphate inhibits glycogenolysis and gluconeogenesis, causing severe hypoglycemia following ingestion of fructose. Prolonged fructose ingestion in infants leads ultimately to hepatic failure and death. Patients develop a strong distaste for sweet food, and avoid a chronic course of the disease by remaining on a fructose- and sucrose-free diet. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] 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] 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

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the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] 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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also

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enterogastritis. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrointestinal Transit: Passage of food (sometimes in the form of a test meal) through the gastrointestinal tract as measured in minutes or hours. The rate of passage through the intestine is an indicator of small bowel function. [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] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] 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] Geriatric: Pertaining to the treatment of the aged. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [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]

Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and

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immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] 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] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] 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] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granisetron: A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into

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three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Haematemesis: The vomiting of blood. [EU] Hallucinogens: Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. [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 Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH]

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Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH]

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Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [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] 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] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperkinesia: Abnormally increased motor function or activity; hyperactivity. [EU] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Pulmonary: Increased pressure within the pulmonary circulation, usually secondary to cardiac or pulmonary disease. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to

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an increase in the number of cells. [NIH] Hypnotherapy: Sleeping-cure. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [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] 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] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] 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

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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] Imperforate Anus: A birth defect in which the anal canal fails to develop. The condition is treated with an operation. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH]

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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] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [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] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestinal Pseudo-Obstruction: Obstruction of the intestines that is functional, not mechanical. [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] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intralaminar Thalamic Nuclei: Cell groups within the internal medullary lamina of the thalamus. They include a rostral division comprising the paracentral, central lateral, central dorsal, and central medial nuclei, and a caudal division composed of the centromedian and parafascicular nuclei. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH]

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Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] 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] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lactation: The period of the secretion of milk. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lactobacillus acidophilus: A species of gram-positive, rod-shaped bacteria isolated from the intestinal tract of humans and animals, the human mouth, and vagina. This organism produces the fermented product, acidophilus milk. [NIH] Lactobacillus casei: A rod-shaped bacterium isolated from milk and cheese, dairy products and dairy environments, sour dough, cow dung, silage, and human mouth, human intestinal contents and stools, and the human vagina. [NIH] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] Lactulose: A mild laxative. [NIH] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large

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intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [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] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lerisetron: A drug that prevents or reduces nausea and vomiting. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [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] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and

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water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Loc: A brain region associated with object recognition. [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] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for

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measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] 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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Maple Syrup Urine Disease: A genetic disorder involving deficiency of an enzyme necessary in the metabolism of branched-chain amino acids, and named for the characteristic odor of the urine. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH]

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Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Assistance: Financing of medical care provided to public assistance recipients. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic

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movements of the face and limbs. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [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] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [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] 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] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Micturition: The passage of urine; urination. [EU] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU]

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Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [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] Motilin: A 22-amino acid polypeptide (molecular weight 2700) isolated from the duodenum. At low pH it inhibits gastric motor activity, whereas at high pH it has a stimulating effect. [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 Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Motor Skills: Performance of complex motor acts. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] 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

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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 sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscarine: A toxic alkaloid found in Amanita muscaria (fly fungus) and other fungi of the Inocybe species. It is the first parasympathomimetic substance ever studied and causes profound parasympathetic activation that may end in convulsions and death. The specific antidote is atropine. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle 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 Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriasis: Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in Adie syndrome. [NIH]

Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myenteric: On stimulation of an intestinal segment, the segment above contracts and that below relaxes. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of

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muscles. [NIH] Myristate: Pharmacological activator of protein kinase C. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [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] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] 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] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

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Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

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] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is

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effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nodose: Having nodes or projections. [EU] Nonulcer Dyspepsia: Constant pain or discomfort in the upper GI tract. Symptoms include burning, nausea, and bloating, but no ulcer. Possibly caused by muscle spasms. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occult Blood: Chemical, spectroscopic, or microscopic detection of extremely small amounts of blood. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU]

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Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oculomotor Nerve: The 3d cranial nerve. The oculomotor nerve sends motor fibers to the levator muscles of the eyelid and to the superior rectus, inferior rectus, and inferior oblique muscles of the eye. It also sends parasympathetic efferents (via the ciliary ganglion) to the muscles controlling pupillary constriction and accommodation. The motor fibers originate in the oculomotor nuclei of the midbrain. [NIH] Office Management: Planning, organizing, and administering activities in an office. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

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] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU]

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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] Ovariectomy: The surgical removal of one or both ovaries. [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] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]

Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH]

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Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [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] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasympathomimetic: 1. Producing effects resembling those of stimulation of the parasympathetic nerve supply to a part. 2. An agent that produces effects similar to those produced by stimulation of the parasympathetic nerves. Called also cholinergic. [EU] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs.

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[NIH]

Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] 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] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [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] 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]

Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs

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of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [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] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to

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avoid. The individual recognizes the fear as excessive or unreasonable. [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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physician-Patient Relations: The interactions between physician and patient. [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 Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Pirenzepine: An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as cimetidine and ranitidine. It is generally well tolerated by patients. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [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]

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Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] 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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

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Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [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] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [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 Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, 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] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is

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indicated, except adrenal deficiency states. [NIH] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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] 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] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Professional-Patient Relations: Interactions between health personnel and patients. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH]

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Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [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] Propulsive: Tending or having power to propel; driving onward or forward; impelling to action or motion. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the

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secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Proton Pump Inhibitors: Medicines that stop the stomach's acid pump. Examples are omeprazole (oh-MEH-prah-zol) (Prilosec) and lansoprazole (lan-SOH-prah-zol) (Prevacid). [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] Prune Belly Syndrome: A syndrome characterized by abdominal wall musculature deficiency, cryptorchism, and urinary tract abnormalities. The syndrome derives its name from its characteristic distended abdomen with wrinkled skin. [NIH] 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] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH]

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Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychological Techniques: Methods used in the diagnosis and treatment of behavioral, personality, and mental disorders. [NIH] Psychological Tests: Standardized tests designed to measure abilities, as in intelligence, aptitude, and achievement tests, or to evaluate personality traits. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Public Assistance: Financial assistance to impoverished persons for the essentials of living through federal, state or local government programs. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Housing: Housing subsidized by tax funds, usually intended for low income persons or families. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH]

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Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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] Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign

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conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] 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] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH]

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Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a 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]

Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [NIH] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Research Support: Financial support of research activities. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [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] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which

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pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] 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] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] 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] Saccharomyces: A genus of ascomycetous fungi of the family Saccharomycetaceae, order saccharomycetales. [NIH] Saccharomyces cerevisiae: A species of the genus Saccharomyces, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. [NIH] Saccharomycetales: An order of fungi in the phylum Ascomycota that multiply by budding. They include the telomorphic ascomycetous yeasts which are found in a very wide range of habitats. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonellosis: Infection by salmonellae. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarin: An organophosphorous ester compound that produces potent and irreversible inhibition of cholinesterase. It is toxic to the nervous system and is a chemical warfare agent. [NIH]

Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH]

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Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] 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] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [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] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self 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] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [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

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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] Sensory Thresholds: The minimum amount of stimulus energy necessary to elicit a sensory response. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] 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]

Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [NIH] Sick Role: Behavior patterns consistent with those expected of an individual functioning in a state of ill health. [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] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH]

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Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silage: Fodder converted into succulent feed for livestock through processes of anaerobic fermentation (as in a silo). [NIH] Simethicone: A mixture of dimethyl polysiloxanes and silica gel used as an antiflatulent. Without the addition of silica gel (dimethicone), it is used as an ointment base ingredient and skin protectant. [NIH] Sincalide: A polypeptide hormone present in the intestine and brain. When secreted from the gastric mucosa, it stimulates the release of both bile from the gallbladder, and the release of digestive enzymes from the pancreas. [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 apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] 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,

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27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] 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] Spasmolytic: Checking spasms; antispasmodic. [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] 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

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orifice; called also musculus sphincter. [EU] Sphincter of Oddi: The muscle between the common bile duct and pancreatic ducts. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sprue: A non febrile tropical disease of uncertain origin. [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] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] 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] Stool test: A test to check for hidden blood in the bowel movement. [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 management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size,

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stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Supraspinal: Above the spinal column or any spine. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

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] 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]

Dictionary 319

Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic 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] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [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] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [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] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH]

320 Irritable Bowel Syndrome

Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [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] Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are antithryoid agents and/or free radical scavengers. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] Time Management: Planning and control of time to improve efficiency and effectiveness. [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] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU]

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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] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trimebutine: Proposed spasmolytic with possible local anesthetic action used in gastrointestinal disorders. [NIH] Trinitrobenzenesulfonic Acid: A reagent that is used to neutralize peptide terminal amino groups. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH]

322 Irritable Bowel Syndrome

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] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

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]

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 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.

Dictionary 323

[NIH]

Urinary urgency: Inability to delay urination. [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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] 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] Vagal: Pertaining to the vagus nerve. [EU] 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] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] 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] Veins: The vessels carrying blood toward the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU]

324 Irritable Bowel Syndrome

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] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] 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] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] War: Hostile conflict between organized groups of people. [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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [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] 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]

325

INDEX A Abdomen, 173, 194, 229, 230, 247, 256, 267, 270, 273, 285, 288, 298, 307, 317, 320, 323, 324 Abdominal Cramps, 226, 247 Aberrant, 172, 247, 261 Absenteeism, 17, 22, 195, 247 Acetylcholine, 55, 61, 142, 147, 148, 170, 247, 260, 288, 296 Actin, 144, 247, 293 Action Potentials, 136, 179, 247 Activities of Daily Living, 161, 247 Adaptation, 247, 303 Adenine, 247, 309 Adenosine, 142, 247, 257, 302 Adhesions, 58, 247 Adrenal Cortex, 247, 265 Adrenal Medulla, 247, 258, 272, 273, 296 Adrenergic, 30, 60, 247, 249, 250, 252, 269, 273, 288, 318, 322 Adverse Effect, 62, 145, 248, 314 Aerobic, 50, 248, 291 Aerobic Exercise, 50, 248 Aerophagia, 186, 248 Afferent, 31, 35, 42, 46, 47, 50, 60, 106, 166, 248, 305, 314 Affinity, 49, 58, 61, 248, 253, 267, 315 Age Groups, 194, 195, 248 Aged, 80 and Over, 248 Agonist, 30, 49, 155, 167, 168, 169, 170, 178, 220, 248, 269, 294, 296 Agoraphobia, 248, 299, 301 Airway, 94, 145, 248, 315 Akathisia, 248, 252 Alertness, 248, 257 Alexia, 248, 270 Algorithms, 248, 255 Alkaline, 248, 249, 254, 257, 298 Alkaloid, 248, 253, 257, 261, 292, 293, 296, 302 Allergen, 248, 267, 314 Allergic Rhinitis, 165, 166, 248 Allylamine, 249 Aloe, 123, 137, 249 Alpha-1, 249 Alternative medicine, 206, 249 Amenorrhea, 249, 250 Amine, 44, 249, 281

Amino Acid Sequence, 157, 249, 251, 306 Amino Acids, 156, 162, 249, 289, 295, 300, 303, 307, 314, 322 Amitriptyline, 193, 249 Ammonia, 249, 279 Amphetamines, 249, 261 Ampulla, 249, 272 Amygdala, 34, 249, 254, 287, 314, 320 Anaesthesia, 249, 284 Anal, 15, 25, 67, 186, 249, 273, 275, 284 Analgesic, 8, 36, 49, 168, 177, 250, 268, 290, 292, 297, 321 Analog, 61, 250 Analogous, 39, 145, 250, 270, 303, 321 Anatomical, 59, 250, 253, 256, 264, 268, 284, 295, 313 Anemia, 21, 250, 281 Anesthesia, 100, 248, 250, 266, 271, 305 Anesthetics, 61, 250, 254, 273 Aneurysm, 250, 323 Angina, 136, 165, 166, 179, 250, 296 Angina Pectoris, 136, 179, 250 Angioplasty, 165, 166, 250 Angiotensin converting enzyme inhibitor, 45, 250 Animal model, 39, 42, 49, 54, 63, 250 Anions, 250, 286 Anomalies, 24, 250, 293 Anorexia, 21, 31, 148, 153, 170, 171, 176, 249, 250, 277, 322 Anorexia Nervosa, 21, 153, 250 Antagonism, 95, 106, 145, 250, 257 Anterograde, 44, 250 Anti-Anxiety Agents, 14, 250, 305, 308, 321 Antibacterial, 251, 316 Antibiotic, 4, 154, 250, 251, 300, 305, 316 Antibiotic Prophylaxis, 251, 305 Antibodies, 44, 59, 142, 160, 172, 180, 251, 280, 283, 289, 303, 309 Antibody, 44, 172, 248, 251, 262, 280, 282, 283, 284, 290, 309, 310, 314, 316 Anticholinergic, 14, 21, 135, 145, 146, 192, 193, 249, 251 Anticoagulant, 251, 306 Anticonvulsant, 135, 251, 291 Antidepressant, 14, 22, 45, 86, 131, 146, 167, 192, 249, 251

326 Irritable Bowel Syndrome

Antidepressive Agents, 251, 308 Antidote, 251, 293 Antiemetic, 251, 252, 269, 279, 291 Antigen, 172, 180, 248, 251, 262, 278, 282, 283, 284, 290, 314 Antihypertensive, 251, 295 Anti-inflammatory, 4, 36, 45, 251, 256, 265, 278 Antineoplastic, 251, 265, 296 Antineoplastic Agents, 251, 296 Antiproliferative, 28, 251 Antipsychotic, 135, 251, 295, 321 Antispasmodic, 8, 18, 26, 233, 252, 297, 316 Anus, 249, 252, 253, 254, 256, 272, 275, 310 Anxiety Disorders, 33, 63, 252, 299 Anxiolytic, 146, 252, 297 Apnea, 143, 155, 163, 252 Apoptosis, 157, 252 Appendectomy, 23, 252 Applicability, 15, 252 Aptitude, 252, 308 Aqueous, 252, 254, 266 Arachidonic Acid, 252, 306 Arginine, 252, 296 Arrhythmia, 61, 136, 179, 252, 324 Arrhythmogenic, 147, 252 Arterial, 249, 252, 264, 282, 307, 319 Arteries, 166, 252, 256, 265, 291, 293, 309 Arterioles, 252, 256, 293 Arthralgia, 167, 168, 253 Articular, 253, 287, 298 Assay, 29, 74, 170, 253, 283, 322 Astrocytes, 253, 292 Asymptomatic, 253, 298 Atresia, 196, 253 Atrial, 178, 253, 264, 321 Atrioventricular, 253, 264 Atrium, 253, 264, 321, 323 Atrophy, 253, 288 Atropine, 135, 253, 254, 268, 293 Attenuation, 13, 32, 253 Atypical, 152, 253 Auditory, 98, 253, 289, 305, 323 Autodigestion, 253, 298 Autoimmune disease, 141, 164, 253, 293 Autonomic, 22, 30, 31, 33, 34, 47, 50, 52, 57, 58, 63, 67, 68, 78, 127, 142, 146, 148, 153, 159, 247, 252, 253, 254, 296, 300, 316, 318 Autonomic Nervous System, 31, 57, 67, 148, 253, 254, 300, 316, 318

Autonomic Pathways, 47, 253 B Bactericidal, 157, 254, 274 Bacteriophage, 254, 303, 321 Bacterium, 254, 286 Bacteriuria, 254, 322 Barbiturates, 170, 171, 254, 313 Barium, 4, 17, 209, 225, 244, 254 Barium enema, 4, 17, 209, 244, 254 Basal Ganglia, 148, 252, 254, 260, 277, 283, 287 Basal Ganglia Diseases, 254, 260, 283 Base, 42, 137, 174, 181, 247, 254, 267, 276, 286, 315, 319, 322 Basophils, 254, 280, 287 Behavior Therapy, 22, 254 Belching, 186, 248, 254 Belladonna, 253, 254 Benign, 16, 165, 166, 192, 254, 277, 280, 294, 309 Benzene, 254 Benzodiazepines, 170, 171, 254 Bereavement, 48, 255 Bile, 172, 180, 255, 260, 277, 278, 288, 315, 317 Bile Acids, 255, 278, 317 Bile Acids and Salts, 255 Biliary, 255, 262, 298 Biliary Tract, 255, 298 Binding Sites, 147, 255 Biochemical, 5, 17, 29, 52, 139, 149, 166, 230, 255, 298, 314 Biological Markers, 22, 173, 255 Biological therapy, 255, 280 Biomechanics, 32, 255 Biopsy, 81, 255 Biosynthesis, 252, 255, 302, 314 Biotechnology, 64, 191, 206, 219, 255 Biotransformation, 255, 301 Bipolar Disorder, 170, 171, 256 Bivalent, 174, 256 Blood Cell Count, 4, 256, 281 Blood Coagulation, 256, 257, 320 Blood Platelets, 256, 314 Blood pressure, 251, 256, 258, 260, 282, 283, 292, 301, 309, 314, 316 Body Fluids, 256, 270, 315 Body Mass Index, 58, 256 Body Regions, 60, 256 Bowel Movement, 9, 15, 16, 30, 58, 146, 208, 209, 227, 256, 257, 264, 268, 317 Bradycardia, 143, 163, 256

Index 327

Bradykinin, 256, 296 Branch, 241, 256, 271, 278, 289, 295, 299, 301, 308, 316, 319, 320 Breakdown, 172, 256, 268, 277 Bromelain, 137, 256 Bromine, 162, 256 Bronchi, 256, 257, 273, 321 Bronchial, 256, 281 Bronchitis, 165, 166, 257, 260 Buccal, 257, 289 Buffers, 57, 257 Bulimia, 143, 148, 163, 170, 171, 257 Bulking Agents, 20, 257 Bupivacaine, 257, 287 C Caffeine, 8, 185, 196, 230, 232, 245, 257, 309 Calcium, 10, 35, 55, 113, 115, 144, 145, 176, 192, 257, 262, 295, 315, 324 Calcium channel blocker, 115, 176, 192, 257, 324 Calcium Channel Blockers, 176, 192, 257 Cannabidiol, 257 Cannabinoids, 49, 257 Cannabinol, 257 Capsaicin, 35, 149, 168, 257 Capsules, 9, 113, 177, 257, 269, 278 Carbohydrate, 79, 111, 257, 265, 279, 303 Carbon Dioxide, 143, 163, 257, 266, 275, 277, 311, 323 Carboxy, 159, 258 Carcinogen, 258, 320 Carcinogenic, 254, 258, 285, 305, 317 Cardia, 148, 258 Cardiorespiratory, 248, 258 Cardiovascular, 142, 148, 153, 154, 168, 169, 258, 302, 314, 316 Cardiovascular disease, 154, 258 Cardiovascular System, 148, 258 Case report, 258, 261 Case series, 258, 261 Catalyse, 179, 258 Catecholamine, 251, 258, 269, 301 Catheterization, 250, 258 Cations, 258, 286 Caudal, 258, 268, 283, 285, 304 Causal, 258, 273, 285 Cecum, 33, 258, 286 Celiac Disease, 64, 258 Cell Death, 252, 258, 278, 294 Cell Differentiation, 258, 315

Cell Division, 43, 253, 259, 280, 290, 291, 302, 306 Cell Lineage, 57, 259 Cell membrane, 136, 179, 257, 259, 267, 277, 302, 304 Cell proliferation, 259, 315 Cell Respiration, 259, 291, 311 Cell Size, 43, 259 Cell Survival, 259, 280 Central Nervous System Infections, 259, 280 Cerebellum, 259, 265, 275 Cerebral Palsy, 259, 316 Cerebrospinal, 157, 259 Cerebrospinal fluid, 157, 259 Cerebrovascular, 254, 257, 258, 259 Cerebrum, 259, 265, 319 Cervical, 44, 259 Cervix, 259 Character, 250, 259, 266, 279 Chemical Warfare, 259, 312 Chemoreceptor, 252, 259 Chemotherapy, 260, 279 Chest Pain, 36, 38, 40, 149, 185, 194, 260 Chimeras, 61, 260 Chlorine, 162, 260 Cholangitis, 196, 260 Cholecystectomy, 45, 260 Cholecystitis, 196, 260 Cholecystokinin, 14, 35, 260, 268 Cholelithiasis, 45, 260 Cholesterol, 45, 255, 260, 265, 277, 317 Cholinergic, 55, 70, 146, 170, 249, 252, 260, 296, 299, 314 Chorea, 170, 171, 252, 260 Choreatic Disorders, 260 Chromatin, 252, 260, 273, 295, 316 Chronic Disease, 5, 86, 150, 233, 260 Chronic Fatigue Syndrome, 50, 129, 140, 141, 164, 190, 193, 224, 260 Chronic Obstructive Pulmonary Disease, 136, 155, 165, 166, 167, 168, 179, 260 Chronic renal, 260, 303, 322 Chylomicrons, 35, 260 Chymopapain, 260, 299 Cimetidine, 260, 302 CIS, 51, 261 Cisplatin, 261, 297 Clamp, 43, 261 Claudication, 136, 179, 261 Clinical study, 110, 115, 261, 264

328 Irritable Bowel Syndrome

Clinical trial, 8, 9, 26, 28, 38, 39, 72, 92, 94, 102, 129, 131, 171, 219, 261, 264, 293, 307, 310 Clitoral, 166, 261 Cloning, 255, 261 Coca, 261 Cocaine, 156, 170, 171, 261 Cofactor, 261, 307, 320 Cognition, 142, 148, 261, 295 Cognitive behavior therapy, 65, 119, 261 Cognitive restructuring, 41, 261, 317 Cognitive Therapy, 36, 40, 261 Cohort Studies, 262, 273 Colitis, 42, 57, 98, 121, 161, 176, 185, 187, 188, 189, 196, 224, 227, 231, 233, 262, 286 Collagen, 140, 256, 262, 275, 278, 303, 305 Collapse, 256, 262, 315 Colonoscopy, 4, 17, 135, 194, 208, 209, 225, 230, 262 Colorectal, 34, 46, 52, 59, 74, 80, 87, 113, 154, 224, 262 Colorectal Cancer, 154, 224, 262 Combinatorial, 151, 262 Commensal, 57, 262 Common Bile Duct, 262, 317 Comorbidity, 29, 37, 54, 72, 262 Complement, 262, 263, 314 Complementary and alternative medicine, 62, 119, 126, 263 Complementary medicine, 119, 263 Complete remission, 263, 311 Computational Biology, 219, 263 Computed tomography, 208, 263 Computerized axial tomography, 263 Computerized tomography, 263 Conception, 263, 264, 275, 317 Concomitant, 24, 263 Congestion, 150, 252, 263 Congestive heart failure, 165, 166, 263 Connective Tissue, 262, 263, 275, 277, 278, 289, 300, 312, 319 Consciousness, 250, 264, 267, 269, 319 Constrict, 264, 293 Constriction, 264, 297, 323 Constriction, Pathologic, 264, 323 Consultation, 38, 85, 264 Consumption, 154, 172, 180, 264, 277, 298 Continence, 25, 264 Contraceptive, 58, 264 Contractility, 43, 142, 264 Contraindications, ii, 23, 193, 264 Contralateral, 44, 264, 290, 297

Control group, 62, 264 Controlled clinical trial, 36, 93, 264, 310 Controlled study, 86, 96, 264 Conventional therapy, 130, 264 Conventional treatment, 264 Convulsions, 136, 179, 251, 264, 293 Convulsive, 148, 264 Coordination, 39, 259, 264, 293 Cor, 50, 52, 58, 153, 159, 264, 306 Coronary, 136, 165, 166, 179, 224, 250, 258, 265, 291, 293, 296 Coronary Circulation, 250, 265 Coronary heart disease, 179, 258, 265 Coronary Thrombosis, 265, 291, 293 Corpus, 265, 300, 320 Cortex, 32, 44, 148, 265, 272, 274, 275, 305, 309 Cortical, 39, 51, 265, 274, 305, 313 Cortices, 44, 265 Corticosteroid, 265, 304 Cortisol, 53, 130, 265 Cranial, 30, 134, 156, 158, 159, 162, 259, 265, 280, 297, 300, 323 Craniocerebral Trauma, 254, 265, 280 Cromolyn Sodium, 96, 265 Cross-Sectional Studies, 265, 273 Cues, 58, 265 Curare, 266, 293 Curative, 266, 320 Cutaneous, 32, 36, 71, 87, 100, 266, 286, 289 Cyclic, 102, 155, 156, 162, 165, 166, 257, 266, 280, 296, 302, 304, 306, 313 Cystitis, 28, 53, 63, 231, 266 Cystoscopy, 28, 266 Cytokine, 53, 172, 180, 266 Cytoplasm, 252, 254, 259, 266, 273, 279, 295 Cytoskeleton, 43, 266 Cytotoxic, 257, 266, 297, 309, 310, 315 Cytotoxic chemotherapy, 266, 297 D Dairy Products, 154, 232, 266, 286 Data Collection, 104, 266 Databases, Bibliographic, 219, 266 Deamination, 266, 292 Decarboxylation, 266, 281 Defecation, 4, 12, 15, 17, 24, 139, 178, 181, 193, 195, 200, 209, 266 Defense Mechanisms, 172, 266 Degenerative, 40, 266, 281, 292, 298 Deglutition, 144, 163, 266

Index 329

Deletion, 252, 266 Delirium, 252, 266 Delivery of Health Care, 267, 280 Delusions, 267, 280, 308 Dementia, 136, 147, 148, 165, 166, 170, 171, 179, 252, 267 Dendrites, 267, 295 Density, 4, 53, 256, 267, 297 Dental Caries, 267, 275 Depersonalization, 267, 299, 313 Depolarization, 267, 315 Derealization, 267, 299 Dermatitis, 152, 267, 270 Descending Colon, 78, 267 Desensitization, 168, 267 Desipramine, 45, 131, 193, 267 Deuterium, 268, 282 Devazepide, 35, 268 Diabetes Mellitus, 5, 268, 279, 281 Diagnostic procedure, 133, 206, 209, 268 Diarrhoea, 65, 67, 111, 136, 148, 149, 154, 179, 268, 277 Diastolic, 268, 282 Diencephalon, 268, 273, 283, 305, 319, 320 Dietary Fats, 268, 288 Dietary Fiber, 17, 18, 24, 224, 227, 228, 229, 232, 268 Dietitian, 25, 184, 185, 188, 268 Digestive system, 132, 186, 228, 229, 268, 278 Digestive tract, 40, 176, 184, 227, 228, 229, 230, 232, 268, 315 Dihydrotestosterone, 268, 311 Dilatation, 250, 268, 323 Dilatation, Pathologic, 268, 323 Dilation, 166, 256, 268, 293, 323 Dimethyl, 156, 268, 288, 295, 315 Diphenoxylate, 167, 268 Direct, iii, 29, 35, 37, 51, 54, 57, 62, 75, 211, 220, 261, 268, 269, 311, 319 Disinfectant, 268, 274 Disposition, 194, 268 Dissociation, 43, 66, 248, 268 Dissociative Disorders, 269 Distal, 16, 33, 57, 59, 60, 75, 166, 269, 278, 307 Distention, 16, 34, 46, 52, 56, 59, 78, 81, 100, 137, 139, 243, 269 Diuresis, 257, 269 Diuretic, 269, 316 Diurnal, 53, 269 Diverticula, 269

Diverticulitis, 196, 224, 269 Diverticulum, 269 Dizziness, 269, 299 Dominance, 93, 269 Domperidone, 105, 269 Dopamine, 44, 105, 148, 151, 152, 156, 252, 261, 269, 291, 292 Dorsal, 43, 46, 269, 273, 285, 304, 314, 317 Dorsum, 269, 277 Dosage Forms, 156, 176, 269 Dose-dependent, 158, 269 Drive, ii, vi, 4, 6, 11, 12, 14, 109, 152, 184, 192, 208, 230, 231, 269 Drug Design, 49, 270 Drug Interactions, 193, 212, 270 Drug Tolerance, 270, 320 Duct, 249, 258, 260, 262, 270, 274, 312, 323 Dumping Syndrome, 158, 270 Duodenal Ulcer, 167, 168, 270, 302 Duodenum, 14, 35, 255, 270, 272, 277, 286, 292, 298, 317 Dynorphins, 270, 297 Dysentery, 23, 176, 270 Dyskinesia, 148, 170, 171, 252, 270 Dyslexia, 170, 171, 270 Dysmenorrhea, 58, 136, 179, 270 Dysmenorrhoea, 165, 166, 270 Dyspareunia, 58, 270 Dyspepsia, 38, 76, 82, 102, 116, 146, 147, 149, 169, 181, 186, 187, 204, 230, 270, 284 Dysphagia, 31, 185, 270 Dysphoria, 151, 270 Dyspnea, 270, 299 Dystonia, 140, 170, 171, 252, 270 Dysuria, 58, 270 E Eating Disorders, 31, 79, 148, 150, 152, 155, 270 Eczema, 29, 150, 270 Edema, 165, 166, 270, 322 Effector, 247, 262, 271, 295, 302 Effector cell, 271, 295 Efficacy, 9, 20, 24, 25, 26, 39, 46, 62, 63, 67, 77, 105, 110, 130, 158, 270, 271 Ejaculation, 142, 151, 271, 313 Elastin, 262, 271 Elective, 23, 271 Electrocardiogram, 13, 271 Electrolyte, 135, 265, 267, 271, 304, 316, 322 Electrons, 254, 271, 286, 309, 310

330 Irritable Bowel Syndrome

Electrophysiological, 40, 42, 46, 55, 153, 159, 271 Embryo, 258, 259, 271, 284, 303 Emesis, 142, 151, 169, 271 Emetic, 170, 271 Emodin, 249, 271 Emphysema, 260, 271 Empirical, 30, 54, 271 Endarterectomy, 250, 271 Endocrine System, 271, 295 Endometrial, 58, 271 Endometriosis, 8, 58, 231, 271 Endometrium, 271, 290 Endorphins, 9, 272, 297, 306 Endoscope, 272 Endoscopic, 29, 38, 158, 262, 266, 272, 315 Endoscopy, 38, 138, 158, 220, 227, 272 Endothelial cell, 157, 272, 320 Endothelium, 165, 272, 296 Endothelium, Lymphatic, 272 Endothelium, Vascular, 272 Endothelium-derived, 165, 272, 296 Endotoxic, 272, 288 Endotoxin, 272, 322 End-stage renal, 260, 272, 303 Enema, 225, 272 Enkephalins, 272, 297 Enteric Nervous System, 6, 7, 40, 48, 272 Enteritis, 181, 272 Enterocolitis, 272 Enterocytes, 35, 272 Entorhinal Cortex, 163, 272, 281 Environmental Exposure, 255, 272 Environmental Health, 218, 220, 273 Enzymatic, 112, 257, 263, 267, 273, 281, 299 Eosinophils, 273, 280, 287 Epidemiologic Studies, 27, 58, 255, 273 Epidemiological, 4, 21, 30, 46, 59, 115, 273 Epigastric, 273, 298 Epinephrine, 247, 269, 273, 296, 322 Epithalamus, 268, 273, 287 Epithelial, 57, 172, 180, 273, 279, 281, 298 Epithelial Cells, 57, 172, 180, 273, 281 Epithelium, 38, 272, 273, 277 Erectile, 175, 273, 300 Erection, 166, 273 Erythrocyte Indices, 256, 273 Erythrocytes, 250, 256, 273, 314 Esophageal, 31, 145, 273, 278 Esophageal Achalasia, 145, 273 Esophagitis, 169, 274, 278

Esophagus, 14, 31, 196, 228, 253, 268, 273, 274, 278, 280, 288, 301, 311, 317 Estrogen, 46, 52, 54, 59, 113, 274, 305 Estrogen receptor, 52, 274 Ethanol, 47, 274, 275 Evacuation, 9, 24, 134, 173, 208, 264, 274, 277, 287, 309 Evoke, 192, 274, 317 Excitability, 40, 42, 274, 294 Excitation, 55, 249, 259, 274 Excitatory, 55, 138, 274, 279 Exhaustion, 250, 274 Exocrine, 260, 274, 298 Exogenous, 35, 89, 255, 270, 274, 301 Expiration, 274, 311 Extensor, 274, 307 Extracellular, 142, 253, 263, 274, 275, 315 Extracellular Matrix, 263, 274, 275 Extrapyramidal, 148, 248, 252, 269, 274 F Faecal, 268, 274 Family Planning, 219, 274 Fat, 17, 60, 184, 185, 252, 255, 264, 265, 274, 288, 293, 312, 318 Fatigue, 5, 9, 29, 49, 54, 62, 140, 141, 150, 164, 194, 260, 274, 280 Fatty acids, 17, 79, 274, 306 Feasibility Studies, 40, 274 Febrile, 274, 317 Feces, 264, 274, 275, 317 Feeding Behavior, 31, 275 Fermentation, 76, 79, 112, 205, 275, 315 Fetus, 275, 323 Fibroblasts, 157, 275 Fibrosis, 136, 165, 166, 179, 196, 249, 275, 312, 313 Fissure, 275, 305 Fistula, 275, 277 Fixation, 275, 314 Flatulence, 13, 186, 193, 275 Flatus, 275, 277 Fluorescence, 57, 275 Fluorine, 162, 275 Fold, 275, 291 Food Hypersensitivity, 101, 115, 275 Forearm, 256, 275, 310 Fourth Ventricle, 275, 288, 320 Frameshift, 276, 322 Frameshift Mutation, 276, 322 Free Radical Scavengers, 276, 320 Freeze-dried, 137, 276 Friction, 276, 288

Index 331

Frontal Lobe, 276, 305 Fructose, 14, 29, 81, 196, 276, 285 Fructose Intolerance, 14, 196, 276 Functional Disorders, 22, 32, 63, 193, 208, 276 Functional magnetic resonance imaging, 36, 63, 276 Fundus, 174, 175, 276 Fungi, 276, 277, 285, 291, 293, 312, 324 Fungus, 276, 293 G Galactosemia, 196, 277 Gallbladder, 82, 188, 247, 255, 260, 268, 276, 277, 278, 315 Gallstones, 255, 260, 277 Gamma Rays, 277, 310 Ganglia, 142, 148, 247, 254, 272, 277, 294, 300, 318 Ganglion, 273, 277, 297 Gap Junctions, 277, 319 Gas exchange, 277, 312, 323 Gastric Acid, 148, 170, 171, 261, 277 Gastric Emptying, 21, 35, 76, 277 Gastric Juices, 277, 300 Gastric Mucosa, 277, 300, 315 Gastrin, 261, 277, 282 Gastritis, 38, 196, 277 Gastroduodenal, 158, 277 Gastroenteritis, 64, 205, 256, 277 Gastroenterologist, 19, 26, 107, 111, 184, 185, 278 Gastroesophageal Reflux, 5, 38, 55, 77, 169, 196, 278 Gastroesophageal Reflux Disease, 5, 38, 55, 77, 169, 278 Gastrointestinal Transit, 40, 77, 167, 278 Gelatin, 278, 279, 320 Gene, 34, 40, 51, 52, 57, 171, 191, 255, 269, 278, 282, 303 Gene Expression, 40, 57, 278 General practitioner, 18, 21, 278 Genetics, 129, 226, 269, 278, 301 Genital, 166, 278, 323 Genitourinary, 142, 278, 323 Genotype, 171, 278, 301 Geriatric, 156, 159, 162, 230, 278 Giant Cells, 278, 312 Gland, 153, 159, 247, 278, 289, 298, 299, 302, 313, 317 Glomerular, 278, 285, 311 Glucocorticoid, 34, 278, 304 Gluconeogenesis, 276, 279

Glucose, 268, 277, 279, 281, 316 Glucose Intolerance, 268, 279 Glutamate, 43, 142, 279 Glutamic Acid, 279, 305 Glutamine, 124, 137, 279 Gluten, 8, 258, 279 Glycine, 142, 157, 255, 279, 314 Glycoprotein, 278, 279, 320, 322 Glycosidic, 279, 297 Goats, 266, 279 Goblet Cells, 272, 279 Gonad, 279 Gonadal, 46, 51, 59, 279, 317 Governing Board, 279, 304 Government Agencies, 196, 279, 304 Graft, 279, 282, 284 Gram-positive, 279, 286 Granisetron, 164, 279 Granule, 157, 279 Granulocytes, 279, 315, 324 Growth, 47, 250, 251, 252, 258, 259, 280, 289, 294, 297, 302, 303, 313, 321 Growth factors, 47, 280 Guanylate Cyclase, 280, 296 Gyrus Cinguli, 280, 287 H Haematemesis, 271, 280 Hallucinogens, 280, 308 Haptens, 248, 280 Headache, 13, 29, 153, 170, 171, 257, 280, 305, 314 Headache Disorders, 280 Health Care Costs, 11, 15, 41, 46, 86, 161, 177, 280 Health Expenditures, 280 Health Services, 38, 267, 280 Health Status, 97, 280 Heart attack, 258, 280 Heart failure, 144, 280 Heartburn, 185, 187, 188, 194, 280, 284 Hematocrit, 256, 273, 281 Heme, 281, 303, 304 Hemoglobin, 250, 256, 273, 281, 304 Hemorrhage, 38, 265, 280, 281, 317 Hemostasis, 281, 314 Hepatic, 165, 166, 262, 267, 276, 281, 292, 303 Hepatitis, 196, 281 Hepatocytes, 281 Hepatology, 4, 7, 10, 20, 25, 47, 78, 79, 94, 111, 194, 195, 281 Hereditary, 260, 281, 292, 301

332 Irritable Bowel Syndrome

Heredity, 12, 204, 278, 281 Heritability, 54, 281 Heterogeneity, 7, 248, 281 Heterozygotes, 269, 281 Hippocampus, 281, 287, 314 Histamine, 45, 252, 260, 281, 282, 288, 310 Histidine, 157, 281 Histology, 34, 47, 282 Homeostasis, 30, 282, 316 Homologous, 61, 144, 256, 281, 282, 314, 319 Homozygotes, 269, 282 Hormonal, 14, 38, 58, 166, 253, 265, 282 Horseradish Peroxidase, 44, 282 Host, 57, 154, 172, 180, 254, 262, 282, 283 Hybrid, 282 Hybridization, 34, 282 Hydrolysis, 255, 261, 282, 302, 303, 307 Hydroxylysine, 262, 282 Hydroxyproline, 262, 282 Hyperalgesia, 42, 46, 47, 50, 52, 56, 60, 63, 71, 75, 97, 100, 140, 141, 164, 282 Hyperkinesia, 170, 171, 282 Hypersecretion, 170, 171, 282 Hypersensitivity, Immediate, 282 Hypertension, 135, 136, 142, 144, 148, 151, 165, 166, 170, 171, 179, 257, 258, 280, 282, 322 Hypertension, Pulmonary, 165, 166, 282 Hypertrophy, 43, 265, 282, 321 Hypnotherapy, 22, 24, 25, 84, 87, 113, 121, 184, 192, 204, 283 Hypoglycemia, 153, 276, 283 Hypokinesia, 134, 156, 158, 159, 162, 283, 299 Hypotension, 252, 264, 283 Hypothalamic, 34, 53, 88, 283 Hypothalamus, 52, 253, 268, 283, 287, 302, 306, 314, 320 I Id, 117, 119, 233, 235, 240, 242, 283 Idiopathic, 54, 139, 283, 309, 312 Ileal, 16, 60, 196, 283 Ileum, 57, 258, 283, 286 Imaging procedures, 283, 321 Immune function, 48, 283 Immune response, 172, 251, 253, 265, 280, 283, 314, 318, 324 Immune system, 47, 142, 153, 160, 255, 271, 283, 289, 293, 294, 323, 324 Immunization, 283, 314 Immunoassay, 161, 283

Immunodeficiency, 153, 165, 166, 283 Immunogenic, 283, 288 Immunoglobulins, 161, 283 Immunohistochemistry, 40, 60, 283 Immunologic, 64, 283, 310 Immunology, 63, 180, 248, 282, 283 Immunosuppressive, 45, 279, 283 Immunotherapy, 255, 267, 283 Impairment, 5, 11, 17, 63, 148, 161, 232, 267, 270, 284, 290, 308 Imperforate Anus, 196, 284 Impotence, 273, 284 In vitro, 32, 35, 49, 79, 284, 320 In vivo, 31, 35, 42, 49, 284 Incision, 284, 285 Incompetence, 278, 284 Indicative, 186, 284, 299, 323 Indigestion, 190, 229, 284, 286 Induction, 168, 252, 284, 305 Infancy, 284 Infant, Newborn, 248, 284 Infantile, 150, 284, 288 Infarction, 265, 284, 291, 293 Infertility, 58, 153, 284 Inflammation, 33, 42, 45, 46, 47, 57, 58, 81, 121, 156, 162, 168, 172, 176, 185, 194, 208, 248, 251, 257, 260, 262, 266, 267, 269, 270, 272, 274, 275, 277, 281, 284, 286, 298, 312, 319, 322, 323 Infusion, 33, 284 Ingestion, 31, 140, 154, 175, 276, 284, 303 Inhalation, 285, 303 Initiation, 50, 285, 321 Innervation, 48, 285 Inorganic, 136, 179, 261, 285, 292 Inotropic, 269, 285 Insight, 52, 57, 285 Insomnia, 285, 305, 314 Insulator, 285, 293 Intermittent, 136, 179, 184, 208, 285 Interstitial, 28, 48, 53, 63, 175, 285, 311 Intervention Studies, 16, 285 Intestinal Flora, 172, 180, 285 Intestinal Pseudo-Obstruction, 48, 55, 285 Intestine, 22, 23, 35, 55, 60, 142, 227, 255, 256, 262, 272, 278, 285, 286, 301, 309, 315 Intoxication, 267, 285, 324 Intracellular, 51, 57, 144, 155, 257, 284, 285, 290, 296, 304, 306, 310, 313, 315 Intraepithelial, 172, 180, 285 Intralaminar Thalamic Nuclei, 44, 285 Intravenous, 284, 285

Index 333

Intrinsic, 60, 248, 285 Inulin, 137, 285 Invasive, 8, 172, 180, 285, 289 Involuntary, 140, 254, 260, 285, 293, 311, 316 Ion Channels, 42, 43, 61, 136, 142, 179, 253, 285, 295, 319 Ionizing, 273, 286, 309 Ions, 136, 179, 254, 257, 268, 271, 282, 286, 292, 304 Irritants, 286 J Jejunum, 81, 286 Jet lag, 170, 171, 286 Joint, 51, 253, 286, 298, 319 K Kb, 218, 286 Kidney Disease, 131, 132, 136, 179, 208, 218, 225, 234, 286 Kidney Pelvis, 286, 322 Kinetics, 57, 286 L Lactation, 286, 298, 305 Lactobacillus, 76, 110, 112, 124, 137, 154, 172, 180, 286 Lactobacillus acidophilus, 137, 286 Lactobacillus casei, 172, 286 Lactose Intolerance, 14, 196, 207, 232, 286 Lactulose, 78, 96, 113, 286 Lag, 286 Large Intestine, 173, 176, 207, 258, 262, 268, 285, 286, 310, 315 Larynx, 287, 321, 323 Latent, 287, 304 Lavage, 135, 287 Laxative, 134, 271, 286, 287, 316 Least-Squares Analysis, 287, 311 Lerisetron, 164, 287 Lesion, 181, 287, 288, 319, 322 Lethal, 254, 287 Leukocytes, 157, 254, 256, 273, 279, 287, 295, 301, 322 Library Services, 240, 287 Lidocaine, 32, 177, 287, 291 Ligaments, 265, 287, 311 Ligands, 142, 147, 148, 151, 153, 167, 287 Likelihood Functions, 287, 311 Limbic, 34, 44, 148, 249, 280, 287, 305 Limbic System, 148, 249, 280, 287, 305 Linear Models, 287, 311 Lipase, 181, 287 Lipid, 35, 92, 114, 288, 293

Lipid A, 35, 288 Lipodystrophy, 196, 288 Lipopolysaccharide, 157, 288 Lithium, 252, 288 Liver, 68, 91, 105, 106, 111, 114, 138, 195, 197, 247, 252, 255, 268, 275, 277, 278, 281, 288, 292, 312 Loc, 142, 288 Localization, 35, 40, 46, 58, 153, 159, 283, 288 Localized, 166, 267, 275, 284, 288, 292, 302, 303, 322 Locus Coeruleus, 33, 44, 288 Logistic Models, 288, 311 Loperamide, 8, 20, 22, 25, 103, 167, 181, 193, 212, 233, 288 Lower Esophageal Sphincter, 273, 278, 288 Lubricants, 288 Lubrication, 166, 288 Luciferase, 51, 288 Lumen, 35, 272, 289 Lupus, 141, 224, 289, 319 Lymph, 35, 259, 272, 289, 312 Lymph node, 259, 289, 312 Lymphatic, 272, 284, 289, 303, 317 Lymphatic system, 289, 317 Lymphocyte, 47, 251, 289, 290 Lymphoid, 172, 180, 251, 289 M Magnetic Resonance Imaging, 32, 289 Malabsorption, 29, 56, 81, 87, 91, 111, 114, 258, 289 Malaise, 270, 289 Malignant, 251, 289, 294, 309 Malnutrition, 60, 253, 289 Manic, 252, 256, 288, 289, 308 Manic-depressive psychosis, 289, 308 Manifest, 24, 40, 289 Maple Syrup Urine Disease, 196, 289 Meat, 150, 256, 268, 289 Meatus, 289, 323 Medial, 32, 44, 280, 285, 289, 297, 314 Mediate, 40, 269, 290, 310 Mediator, 260, 290, 314 Medical Assistance, 138, 290 Medical Records, 29, 45, 290, 312 Medicament, 160, 178, 181, 182, 290 MEDLINE, 18, 219, 290 Medullary, 44, 144, 163, 285, 290, 309 Meiosis, 256, 290, 319 Melanin, 288, 290, 322 Membrane Glycoproteins, 290

334 Irritable Bowel Syndrome

Membrane Proteins, 290, 307 Memory, 61, 136, 147, 148, 179, 250, 267, 290 Menarche, 58, 290 Meninges, 259, 265, 290 Menopause, 290, 300, 304, 305 Menstrual Cycle, 9, 19, 21, 27, 48, 58, 102, 185, 227, 232, 290, 305 Menstruation, 17, 27, 141, 194, 204, 231, 249, 270, 290, 305 Mental Disorders, 132, 283, 290, 307, 308 Mental Health, iv, 5, 7, 28, 65, 132, 184, 218, 221, 224, 290, 308 Mental Processes, 269, 290, 308 Meperidine, 268, 290 Mesencephalic, 288, 290 Mesenteric, 35, 291 Mesentery, 291 Mesolimbic, 252, 291 Meta-Analysis, 26, 77, 291 Metabolite, 156, 255, 268, 291, 305 Metaphase, 256, 291 Methionine, 268, 291, 306 Metoclopramide, 178, 291 Mexiletine, 177, 291 MI, 134, 156, 207, 245, 291 Microbiology, 63, 247, 253, 254, 291 Microorganism, 261, 291, 324 Micro-organism, 154, 172, 180, 267, 291 Microscopy, 34, 282, 291 Micturition, 33, 291 Milligram, 6, 291 Mitochondria, 157, 291 Mitosis, 252, 291 Modeling, 38, 41, 53, 56, 57, 270, 291 Modification, 4, 162, 185, 192, 230, 291, 309 Modulator, 168, 291 Molecular, 34, 40, 51, 52, 59, 61, 63, 219, 222, 255, 263, 270, 291, 292, 305, 310, 321, 322 Molecular Structure, 292, 321 Molecule, 49, 251, 254, 255, 263, 268, 271, 272, 274, 279, 282, 292, 296, 310, 315, 323 Monitor, 228, 292, 296 Monoamine, 73, 151, 152, 156, 251, 292, 322 Monoamine Oxidase, 73, 251, 292, 322 Monocyte, 157, 292 Mononuclear, 292, 322 Monophosphate, 102, 155, 165, 166, 292 Mood Disorders, 10, 292

Morphine, 59, 268, 290, 292, 294, 297 Morphological, 31, 40, 271, 276, 292 Motilin, 14, 292 Motion Sickness, 292, 294 Motor Activity, 75, 264, 292 Motor nerve, 292, 293, 297 Motor Skills, 150, 292 Movement Disorders, 252, 292 Mucins, 272, 279, 292 Mucosa, 31, 57, 135, 172, 180, 258, 260, 272, 277, 289, 292, 305 Mucus, 24, 139, 149, 193, 208, 209, 270, 292, 312, 322 Multicenter Studies, 104, 292 Multicenter study, 96, 293 Multiple sclerosis, 141, 164, 175, 293 Muscarine, 145, 293 Muscle Contraction, 144, 293 Muscle relaxant, 20, 250, 293 Muscle Relaxation, 56, 293 Muscle tension, 293 Musculature, 283, 293, 307 Mutagenesis, 47, 293 Mutagens, 276, 293 Mydriasis, 145, 146, 293 Mydriatic, 268, 293 Myelin, 293 Myenteric, 55, 60, 138, 273, 293 Myocardial Ischemia, 250, 293 Myocardium, 250, 291, 293 Myosin, 293 Myristate, 176, 294 N Naive, 52, 62, 294 Naloxone, 9, 95, 294 Narcolepsy, 136, 156, 179, 294 Narcosis, 294 Narcotic, 177, 290, 292, 294, 321 NCI, 1, 132, 217, 261, 294 Necrosis, 252, 284, 291, 293, 294, 312 Neonatal, 42, 294 Neoplasms, 251, 294, 309 Nephropathy, 286, 294 Nephrosis, 294 Nephrotic, 165, 166, 294 Networks, 172, 180, 294 Neural, 30, 32, 33, 42, 47, 51, 59, 60, 248, 267, 292, 294, 314 Neural Pathways, 60, 294 Neuroanatomy, 30, 287, 295 Neuroendocrine, 22, 47, 50, 64, 148, 295 Neuroendocrinology, 6, 34, 295

Index 335

Neurofilaments, 44, 295 Neurogenic, 173, 174, 295 Neuroleptic, 248, 252, 295, 297 Neurologic, 250, 295 Neuromuscular, 247, 295, 322 Neuromuscular Junction, 247, 295 Neuronal, 34, 35, 40, 43, 47, 50, 51, 52, 156, 157, 170, 294, 295, 300 Neuropathy, 81, 156, 167, 168, 295 Neuropeptide, 149, 295 Neuropharmacology, 47, 295 Neurophysiology, 34, 267, 295 Neurosis, 295, 301 Neurotic, 167, 168, 250, 295 Neurotransmitters, 55, 152, 155, 249, 292, 295, 314, 316 Neutrophils, 280, 287, 295 Nicardipine, 10, 295 Nicotine, 148, 156, 170, 171, 185, 296 Nitric Oxide, 102, 165, 296 Nitrogen, 145, 248, 249, 275, 279, 296, 321 Nodose, 35, 296 Nonulcer Dyspepsia, 40, 86, 296 Nonverbal Communication, 296, 308 Norepinephrine, 148, 151, 152, 156, 247, 249, 267, 269, 296, 314 Nuclear, 107, 254, 271, 277, 287, 294, 296, 320 Nuclei, 33, 44, 142, 148, 249, 271, 273, 285, 289, 291, 296, 297, 307, 314 Nucleic acid, 282, 293, 296, 309 Nucleic Acid Hybridization, 282, 296 Nursing Care, 24, 296 O Occult, 138, 296 Occult Blood, 138, 296 Ocular, 296, 302 Oculomotor, 290, 293, 297 Oculomotor Nerve, 293, 297 Office Management, 195, 297 Office Visits, 8, 19, 29, 56, 297 Ointments, 269, 297 Oligosaccharides, 118, 137, 297 Ondansetron, 164, 297 Opacity, 267, 297 Opioid Peptides, 138, 270, 272, 297 Opium, 292, 297 Optic Chiasm, 283, 297 Organ Culture, 297, 320 Orgasm, 166, 271, 297 Orofacial, 52, 297 Orthostatic, 135, 252, 297

Osmosis, 297 Osmotic, 134, 135, 297 Osteoarthritis, 155, 157, 298 Osteoporosis, 113, 298 Outpatient, 86, 298 Ovariectomy, 47, 298 Ovaries, 298, 311, 314 Ovary, 279, 298, 303 Oxides, 174, 298 Oxygen Consumption, 298, 311 Oxytocin, 52, 54, 64, 97, 298 P Pacemaker, 48, 298 Pain Threshold, 56, 62, 205, 298 Palliative, 298, 320 Palsy, 153, 170, 171, 298 Pancreas, 60, 247, 268, 278, 288, 298, 315 Pancreatic, 45, 260, 268, 276, 278, 298, 317 Pancreatic cancer, 45, 298 Pancreatic Ducts, 298, 317 Pancreatic Juice, 278, 298 Pancreatitis, 8, 45, 298 Paneth Cells, 272, 298 Panic, 10, 134, 148, 150, 156, 158, 159, 162, 170, 171, 224, 299 Panic Disorder, 10, 170, 171, 224, 299 Papain, 137, 299 Paralysis, 266, 290, 299, 316 Parasite, 299 Parasitic, 8, 270, 299 Parasympathomimetic, 293, 299 Paresthesias, 299 Parkinsonism, 175, 252, 299 Parotid, 299, 312 Paroxetine, 75, 299 Paroxysmal, 250, 280, 299 Partial remission, 299, 311 Particle, 299, 321 Patch, 43, 299 Pathogenesis, 4, 23, 27, 28, 141, 191, 195, 299 Pathologic, 252, 255, 265, 282, 299, 307 Pathologic Processes, 252, 299 Pathologies, 58, 299 Patient Education, 4, 16, 24, 25, 195, 199, 200, 225, 232, 233, 238, 240, 245, 299 Pelvic, 42, 53, 71, 102, 127, 140, 231, 271, 300 Pelvic inflammatory disease, 231, 300 Penicillin, 250, 300 Penis, 166, 271, 300 Pepsin, 261, 300

336 Irritable Bowel Syndrome

Pepsin A, 261, 300 Peptic, 8, 31, 38, 45, 84, 300 Peptic Ulcer, 8, 31, 45, 84, 300 Peptide, 58, 146, 147, 153, 158, 159, 260, 297, 300, 303, 306, 307, 321 Peptide T, 300, 321 Perception, 7, 14, 25, 36, 51, 53, 56, 97, 102, 106, 220, 267, 280, 300, 313 Perfusion, 35, 276, 300 Pericardium, 300, 319 Perimenopausal, 113, 300 Peripheral Nerves, 300, 317 Peripheral Nervous System, 40, 272, 298, 300, 318 Peripheral Vascular Disease, 142, 165, 166, 300 Peristalsis, 172, 180, 269, 301 Peroxidase, 44, 301 Peroxide, 301 Pharmaceutical Preparations, 177, 274, 278, 301 Pharmaceutical Solutions, 269, 301 Pharmacists, 23, 66, 301 Pharmacogenetics, 6, 115, 301 Pharmacokinetics, 270, 301 Pharmacologic, 13, 16, 20, 24, 37, 39, 50, 60, 89, 98, 107, 191, 192, 250, 301, 321 Pharmacotherapy, 191, 192, 193, 301 Pharynx, 278, 301, 323 Phenotype, 255, 301 Phenyl, 134, 135, 159, 162, 174, 177, 290, 301 Phobia, 10, 301 Phobic Disorders, 301 Phosphodiesterase, 155, 165, 302 Phosphodiesterase Inhibitors, 155, 165, 302 Phospholipases, 302, 315 Phospholipids, 274, 302 Phosphorus, 257, 302 Phosphorylation, 46, 57, 302 Physical Examination, 8, 11, 17, 18, 23, 29, 192, 209, 227, 230, 302 Physician-Patient Relations, 8, 11, 14, 15, 195, 200, 302 Physiologic, 5, 38, 45, 56, 60, 131, 194, 248, 255, 283, 285, 290, 302, 306, 310 Physiology, 16, 17, 30, 31, 33, 38, 40, 44, 51, 97, 105, 180, 184, 229, 232, 247, 255, 271, 278, 295, 302 Pilot Projects, 39, 302 Pilot study, 39, 45, 62, 67, 72, 111, 302

Piperidines, 151, 302 Pirenzepine, 116, 302 Pituitary Gland, 47, 153, 159, 265, 302, 306 Placebo Effect, 15, 26, 38, 302 Plants, 248, 253, 254, 257, 261, 271, 279, 285, 296, 302, 303, 321 Plaque, 250, 303 Plasma, 53, 157, 251, 259, 272, 278, 279, 281, 303, 313 Plasma cells, 251, 303 Plasticity, 31, 303 Platelet Activation, 303, 315 Platelet Aggregation, 296, 303 Platelets, 296, 303 Plexus, 55, 273, 303 Poisoning, 135, 267, 277, 285, 294, 303 Policy Making, 279, 303 Pollen, 153, 303 Polycystic, 136, 179, 303 Polymorphism, 6, 115, 303 Polypeptide, 249, 262, 282, 292, 300, 303, 305, 307, 315, 324 Polyposis, 38, 196, 262, 303 Polysaccharide, 251, 303 Population Dynamics, 154, 303 Porphyria, 196, 303 Porphyrins, 303, 304 Posterior, 32, 249, 259, 269, 273, 298, 304 Postmenopausal, 298, 304 Postnatal, 42, 304 Postoperative, 158, 290, 304 Postprandial, 60, 92, 140, 304 Postsynaptic, 304, 315, 319 Post-traumatic, 153, 280, 292, 304 Post-traumatic stress disorder, 153, 304 Potassium, 136, 304 Potassium Channels, 136, 304 Potentiates, 267, 302, 304 Potentiating, 249, 304 Potentiation, 304, 315 Practicability, 274, 304 Practice Guidelines, 221, 233, 304 Precipitation, 13, 304 Preclinical, 50, 304 Precursor, 252, 269, 271, 272, 273, 296, 304, 305, 306, 321, 322 Predisposition, 13, 54, 141, 304 Prednisolone, 99, 304 Prefrontal Cortex, 32, 305 Premedication, 158, 305 Premenopausal, 58, 305 Premenstrual, 27, 156, 162, 190, 193, 305

Index 337

Premenstrual Syndrome, 156, 162, 190, 193, 305 Presumptive, 54, 305 Presynaptic, 55, 305, 319 Prevalence, 7, 10, 20, 22, 27, 30, 37, 51, 52, 53, 58, 80, 86, 88, 98, 138, 162, 166, 171, 195, 305 Procaine, 287, 305 Proctosigmoiditis, 196, 305 Prodrug, 305 Professional-Patient Relations, 18, 305 Prognostic factor, 28, 305 Progression, 57, 250, 305 Progressive, 56, 60, 153, 170, 171, 258, 260, 267, 270, 280, 294, 298, 303, 305, 311 Projection, 46, 266, 296, 305 Prolactin, 269, 305 Proline, 262, 282, 305 Promoter, 6, 50, 52, 171, 305 Prone, 54, 60, 306 Pro-Opiomelanocortin, 272, 297, 306 Prophase, 256, 306, 319 Prophylaxis, 154, 172, 176, 180, 306 Propulsive, 232, 306 Prospective study, 74, 306 Prostaglandin, 157, 306 Prostaglandins A, 306 Protease, 157, 306 Protective Agents, 257, 306 Protein C, 149, 249, 254, 306 Protein Conformation, 249, 306 Protein Kinases, 144, 307 Protein S, 191, 255, 307 Proteolytic, 249, 262, 299, 307 Protocol, 5, 29, 32, 107, 135, 137, 307 Proton Pump, 45, 307 Proton Pump Inhibitors, 45, 307 Protons, 282, 286, 307, 309 Protozoa, 270, 291, 307 Proximal, 16, 60, 166, 269, 305, 307, 314 Prune Belly Syndrome, 196, 307 Pruritic, 152, 270, 307 Pruritus, 152, 307, 322 Pseudorabies, 33, 307 Psoriasis, 155, 307 Psychiatric, 8, 10, 12, 22, 24, 27, 33, 37, 44, 54, 72, 89, 101, 102, 153, 208, 255, 290, 307 Psychiatry, 10, 37, 72, 84, 88, 89, 106, 275, 307, 318 Psychic, 295, 308, 313 Psychological Techniques, 15, 308

Psychological Tests, 209, 308 Psychology, 32, 36, 40, 82, 185, 268, 308 Psychopathology, 50, 99, 190, 308 Psychophysiology, 38, 308 Psychosis, 136, 148, 151, 170, 171, 179, 251, 308 Psychotherapy, 15, 22, 23, 24, 44, 68, 93, 191, 192, 195, 261, 308, 310 Psychotropic, 8, 20, 25, 308 Psychotropic Drugs, 20, 308 Psyllium, 17, 125, 308 Public Assistance, 290, 308 Public Health, 37, 58, 166, 221, 308 Public Housing, 7, 308 Public Policy, 219, 308 Publishing, 4, 8, 19, 24, 64, 185, 194, 196, 220, 308 Pulmonary, 256, 260, 264, 265, 276, 282, 308, 309, 312, 318, 323 Pulmonary Circulation, 282, 308 Pulmonary Edema, 260, 308 Pulmonary hypertension, 265, 309 Pulmonary Ventilation, 309, 312 Pulse, 143, 292, 309 Pupil, 268, 293, 309 Purgative, 271, 287, 309 Purines, 309, 314 Purulent, 309 Pylorus, 270, 309 Pyoderma, 170, 171, 309 Pyoderma Gangrenosum, 170, 171, 309 Pyramidal Tracts, 274, 309 Q Quaternary, 174, 307, 309 R Race, 15, 156, 309 Radiation, 250, 273, 275, 277, 286, 309, 324 Radioactive, 282, 296, 309 Radiography, 194, 225, 309 Radioimmunotherapy, 309, 310 Radioisotope, 309, 321 Radiotherapy, 154, 309 Radius, 31, 310 Randomized, 5, 8, 9, 20, 26, 39, 46, 62, 65, 77, 86, 95, 96, 98, 99, 107, 110, 113, 114, 119, 271, 310 Randomized clinical trial, 8, 26, 310 Randomized Controlled Trials, 62, 77, 310 Ranitidine, 302, 310 Rape, 304, 310 Reagent, 260, 288, 310, 321 Reality Testing, 308, 310

338 Irritable Bowel Syndrome

Reassurance, 4, 11, 16, 17, 22, 24, 25, 192, 193, 310 Receptors, Serotonin, 310, 314 Recombinant, 40, 61, 142, 181, 310, 323 Recovery of Function, 31, 310 Recur, 11, 310 Recurrence, 256, 289, 302, 310 Reductase, 45, 311 Refer, 1, 196, 257, 262, 269, 272, 275, 276, 288, 294, 295, 308, 309, 311 Reflex, 59, 60, 110, 121, 163, 311 Reflux, 150, 169, 278, 311 Refraction, 311, 316 Refractory, 11, 36, 86, 87, 311 Regeneration, 31, 311 Regimen, 6, 16, 18, 25, 271, 301, 302, 311 Regression Analysis, 12, 311 Regurgitation, 278, 280, 311 Relapse, 47, 57, 311 Relaxant, 311 Relaxation Techniques, 11, 15, 186, 311 Relaxin, 140, 311 Remission, 194, 256, 289, 310, 311 Renal failure, 165, 166, 267, 311 Research Support, 23, 311 Resected, 154, 172, 180, 311 Resection, 196, 311 Respiration, 144, 148, 163, 252, 257, 260, 266, 292, 311 Respiratory distress syndrome, 155, 311 Respiratory System, 168, 311 Response rate, 89, 312 Reticular, 44, 312 Retrograde, 33, 44, 46, 312 Retrospective, 19, 27, 41, 57, 312 Retrospective study, 27, 312 Reversion, 312, 322 Rheumatism, 312 Rheumatoid, 37, 155, 157, 312 Rheumatoid arthritis, 37, 155, 157, 312 Rhinorrhea, 136, 179, 312 Ribose, 247, 312 Rigidity, 31, 299, 302, 312 Risk factor, 4, 23, 28, 37, 45, 58, 100, 101, 186, 231, 273, 288, 306, 312 Rod, 254, 261, 286, 312 S Saccharomyces, 160, 312, 324 Saccharomyces cerevisiae, 160, 312, 324 Saccharomycetales, 312 Salivary, 268, 298, 302, 312, 324 Salivary glands, 268, 312

Salmonellosis, 8, 312 Sarcoidosis, 196, 312 Sarin, 135, 312 Schizoid, 312, 324 Schizophrenia, 151, 170, 171, 313, 324 Schizotypal Personality Disorder, 267, 313, 324 Sclerosis, 141, 153, 154, 170, 171, 293, 313 Screening, 4, 19, 25, 31, 50, 54, 78, 113, 142, 144, 151, 261, 313, 322 Scrotum, 313, 323 Second Messenger Systems, 295, 313 Secretory, 38, 40, 60, 136, 146, 179, 313, 319 Sedative, 249, 313 Sedatives, Barbiturate, 254, 313 Sediment, 313, 322 Segmental, 46, 313 Segmentation, 313 Seizures, 136, 150, 179, 267, 299, 313 Self Care, 247, 313 Sella, 269, 302, 313 Semen, 271, 313 Seminal vesicles, 313, 323 Senile, 170, 171, 298, 313 Sensibility, 249, 282, 313 Sensitization, 42, 46, 47, 49, 51, 60, 314 Sensory Thresholds, 97, 314 Septal, 287, 314 Septal Nuclei, 287, 314 Serine, 144, 157, 314 Serologic, 283, 314 Serous, 272, 314 Serum, 4, 138, 141, 157, 262, 314, 322 Sex Characteristics, 314, 319 Shock, 152, 275, 314, 321 Sibutramine, 155, 156, 314 Sick Role, 56, 314 Side effect, 21, 146, 147, 158, 171, 175, 211, 248, 252, 255, 314, 320 Sigmoid, 78, 228, 305, 314, 315 Sigmoid Colon, 78, 228, 305, 314 Sigmoidoscopy, 4, 17, 53, 138, 209, 230, 244, 315 Signal Transduction, 57, 149, 315 Signs and Symptoms, 231, 311, 315, 322 Silage, 286, 315 Simethicone, 23, 212, 315 Sincalide, 268, 315 Skeletal, 144, 261, 266, 315, 316 Skeleton, 247, 286, 306, 315 Skull, 265, 315, 319 Sleep apnea, 144, 163, 315

Index 339

Small intestine, 16, 29, 59, 172, 180, 192, 228, 258, 260, 270, 272, 282, 283, 285, 286, 315 Smooth muscle, 17, 20, 25, 26, 43, 48, 69, 94, 142, 143, 144, 145, 146, 147, 173, 174, 175, 249, 257, 281, 282, 292, 315, 316, 318 Social Environment, 146, 309, 315 Social Support, 315, 317 Sodium, 134, 315 Solitary Nucleus, 253, 316 Solvent, 254, 274, 297, 301, 316 Soma, 316 Somatic, 9, 41, 56, 59, 69, 190, 287, 290, 291, 300, 305, 316, 323 Sorbitol, 8, 14, 81, 316 Spasm, 8, 252, 264, 290, 316 Spasmodic, 247, 316 Spasmolytic, 135, 147, 316, 321 Spastic, 120, 121, 170, 171, 173, 174, 231, 286, 316 Spasticity, 316 Specialist, 62, 235, 268, 316 Specificity, 3, 61, 248, 316 Spectrum, 37, 141, 149, 153, 159, 168, 316 Sperm, 303, 316 Spermatozoa, 313, 316, 323 Sphincter, 106, 175, 287, 316, 317 Sphincter of Oddi, 106, 317 Spinal Nerves, 34, 300, 317 Spleen, 289, 312, 317 Sprue, 8, 70, 170, 171, 196, 317 Statistically significant, 19, 317 Steel, 261, 317 Sterility, 284, 317 Steroid, 255, 265, 317 Stimulant, 137, 257, 281, 317 Stimulus, 36, 50, 60, 155, 264, 269, 271, 274, 285, 286, 299, 301, 311, 314, 317, 320 Stool, 4, 12, 17, 24, 46, 86, 138, 149, 193, 209, 229, 230, 232, 267, 284, 286, 287, 317, 319 Stool test, 209, 317 Stress management, 40, 184, 229, 233, 317 Stroke, 131, 132, 135, 152, 153, 155, 165, 166, 167, 168, 169, 170, 171, 178, 218, 224, 258, 317 Stromal, 271, 317 Structure-Activity Relationship, 49, 317 Stupor, 294, 318 Subacute, 284, 318 Subarachnoid, 276, 280, 318 Subclinical, 284, 313, 318

Subcutaneous, 271, 288, 318 Sublingual, 21, 318 Subspecies, 316, 318 Substance P, 291, 313, 318 Substrate, 59, 165, 318, 322 Supplementation, 5, 68, 70, 86, 111, 113, 193, 318 Support group, 36, 228, 318 Suppression, 57, 136, 153, 179, 265, 318 Suppressive, 45, 318 Supraspinal, 46, 318 Surfactant, 35, 318 Sympathetic Nervous System, 53, 253, 318 Sympathomimetic, 269, 273, 296, 318, 322 Symptomatic, 5, 9, 18, 22, 45, 48, 53, 149, 250, 298, 318 Symptomatic treatment, 22, 251, 318 Symptomatology, 27, 59, 319 Synapses, 295, 319 Synapsis, 319 Synaptic, 40, 55, 136, 179, 296, 315, 319 Synaptic Transmission, 55, 136, 179, 296, 319 Syncope, 143, 163, 319 Systemic, 141, 164, 212, 256, 267, 273, 284, 304, 312, 319, 321 Systemic lupus erythematosus, 141, 164, 319 Systolic, 282, 319 T Tardive, 148, 170, 171, 252, 319 Telencephalon, 254, 319 Temporal, 22, 31, 61, 249, 280, 281, 289, 319 Temporal Lobe, 249, 319 Tenesmus, 270, 319 Testosterone, 54, 311, 319 Tetrahydrocannabinol, 257, 319 Thalamic, 32, 43, 44, 273, 320 Thalamus, 32, 42, 44, 268, 273, 285, 287, 305, 320 Thermal, 61, 268, 320 Thiourea, 168, 320 Third Ventricle, 273, 283, 320 Thorax, 247, 320, 323 Threonine, 144, 300, 314, 320 Threshold, 50, 274, 282, 320 Thrombin, 303, 306, 320 Thrombomodulin, 306, 320 Thrombosis, 307, 317, 320 Time Management, 317, 320 Tissue Culture, 55, 320

340 Irritable Bowel Syndrome

Tolerance, 26, 172, 279, 320 Tomography, 320 Tonicity, 270, 320 Topical, 274, 299, 320 Toxic, iv, 57, 253, 254, 266, 273, 293, 295, 296, 301, 312, 320, 321 Toxicity, 270, 271, 320 Toxicology, 55, 220, 321 Toxins, 61, 251, 284, 309, 321 Trace element, 275, 321 Tracer, 29, 282, 321 Trachea, 143, 256, 287, 301, 321 Traction, 261, 321 Tramadol, 177, 321 Tranquilizing Agents, 308, 321 Transcription Factors, 51, 321 Transduction, 35, 315, 321 Transfection, 255, 321 Translational, 60, 115, 321 Transmitter, 55, 247, 253, 269, 285, 290, 296, 319, 321, 322 Trauma, 24, 152, 267, 274, 294, 298, 310, 321 Triad, 157, 321 Tricuspid Atresia, 264, 321 Tricyclic, 50, 193, 249, 251, 267, 321 Trigger zone, 252, 321 Trimebutine, 26, 77, 192, 321 Trinitrobenzenesulfonic Acid, 47, 321 Tryptophan, 262, 314, 321 Tuberculosis, 264, 289, 321 Tumor Necrosis Factor, 157, 322 Typhimurium, 157, 322 Tyramine, 292, 322 Tyrosine, 269, 322 U Ulcer, 38, 149, 169, 181, 230, 270, 296, 300, 302, 322 Ulceration, 176, 322 Ulcerative colitis, 8, 27, 38, 87, 93, 154, 157, 160, 170, 171, 194, 195, 284, 309, 322 Ultrasonography, 31, 322 Unconscious, 250, 266, 283, 322 Uraemia, 298, 322 Uremia, 311, 322 Ureter, 142, 286, 322 Urethra, 300, 322, 323 Urinalysis, 138, 322 Urinary tract, 231, 254, 307, 322 Urinary tract infection, 231, 254, 322 Urinary urgency, 173, 174, 323

Urine, 28, 57, 231, 254, 256, 264, 269, 284, 289, 291, 322, 323 Urogenital, 278, 323 Uterine Contraction, 298, 323 Uterus, 58, 166, 259, 265, 271, 276, 290, 298, 323 V Vaccine, 307, 323 Vagal, 31, 35, 273, 323 Vagina, 166, 259, 286, 290, 323 Vaginal, 166, 288, 323 Vagus Nerve, 30, 316, 323 Vas Deferens, 142, 323 Vascular, 43, 136, 157, 179, 249, 257, 272, 280, 282, 284, 296, 323 Vasculitis, 298, 323 Vasoactive, 165, 323 Vasoconstriction, 170, 171, 273, 323 Vasodilation, 166, 323 Vasodilator, 256, 269, 281, 295, 323 Vector, 321, 323 Veins, 256, 289, 303, 323, 324 Venom, 61, 323 Venous, 166, 256, 307, 321, 323 Venous blood, 256, 323 Ventral, 283, 297, 317, 323 Ventricle, 249, 253, 264, 281, 309, 319, 321, 323 Ventricular, 264, 321, 323 Venules, 256, 272, 324 Verapamil, 105, 106, 176, 177, 324 Vertebrae, 317, 324 Veterinary Medicine, 219, 324 Villous, 258, 324 Viral, 157, 278, 321, 324 Virus, 33, 153, 254, 259, 278, 303, 321, 324 Viscera, 63, 178, 291, 316, 324 Visceral Afferents, 253, 323, 324 Vitro, 35, 324 Vivo, 324 Volition, 285, 324 W War, 190, 206, 304, 324 Weight Gain, 155, 324 White blood cell, 251, 287, 289, 292, 303, 324 Withdrawal, 49, 148, 153, 267, 290, 324 Womb, 323, 324 X Xenograft, 250, 324 Xerostomia, 21, 324 X-ray, 227, 254, 263, 275, 277, 296, 310, 324

Index 341

Y Yeasts, 276, 285, 301, 312, 324

Z Zymogen, 306, 324

342 Irritable Bowel Syndrome

Index 343

344 Irritable Bowel Syndrome

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