Crohn's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

CROHN’S DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AME...

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CROHN’S DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Crohn’s Disease: 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: 0-597-83592-6 1. Crohn’s Disease-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 Crohn’s disease. 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 CROHN’S DISEASE .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Crohn’s Disease............................................................................. 7 E-Journals: PubMed Central ....................................................................................................... 71 The National Library of Medicine: PubMed ................................................................................ 74 CHAPTER 2. NUTRITION AND CROHN’S DISEASE......................................................................... 203 Overview.................................................................................................................................... 203 Finding Nutrition Studies on Crohn’s Disease ......................................................................... 203 Federal Resources on Nutrition ................................................................................................. 213 Additional Web Resources ......................................................................................................... 214 CHAPTER 3. ALTERNATIVE MEDICINE AND CROHN’S DISEASE .................................................. 217 Overview.................................................................................................................................... 217 National Center for Complementary and Alternative Medicine................................................ 217 Additional Web Resources ......................................................................................................... 230 General References ..................................................................................................................... 236 CHAPTER 4. DISSERTATIONS ON CROHN’S DISEASE .................................................................... 237 Overview.................................................................................................................................... 237 Dissertations on Crohn’s Disease .............................................................................................. 237 Keeping Current ........................................................................................................................ 238 CHAPTER 5. CLINICAL TRIALS AND CROHN’S DISEASE ............................................................... 239 Overview.................................................................................................................................... 239 Recent Trials on Crohn’s Disease .............................................................................................. 239 Keeping Current on Clinical Trials ........................................................................................... 252 CHAPTER 6. PATENTS ON CROHN’S DISEASE ............................................................................... 255 Overview.................................................................................................................................... 255 Patents on Crohn’s Disease........................................................................................................ 255 Patent Applications on Crohn’s Disease.................................................................................... 281 Keeping Current ........................................................................................................................ 293 CHAPTER 7. BOOKS ON CROHN’S DISEASE ................................................................................... 295 Overview.................................................................................................................................... 295 Book Summaries: Federal Agencies............................................................................................ 295 Book Summaries: Online Booksellers......................................................................................... 296 The National Library of Medicine Book Index ........................................................................... 299 Chapters on Crohn’s Disease ..................................................................................................... 300 Directories.................................................................................................................................. 301 CHAPTER 8. MULTIMEDIA ON CROHN’S DISEASE ........................................................................ 303 Overview.................................................................................................................................... 303 Audio Recordings....................................................................................................................... 303 Bibliography: Multimedia on Crohn’s Disease .......................................................................... 303 CHAPTER 9. PERIODICALS AND NEWS ON CROHN’S DISEASE ..................................................... 307 Overview.................................................................................................................................... 307 News Services and Press Releases.............................................................................................. 307 Newsletters on Crohn’s Disease................................................................................................. 312 Newsletter Articles .................................................................................................................... 313 Academic Periodicals covering Crohn’s Disease........................................................................ 314 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 315 Overview.................................................................................................................................... 315 U.S. Pharmacopeia..................................................................................................................... 315 Commercial Databases ............................................................................................................... 317

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Researching Orphan Drugs ....................................................................................................... 317 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 321 Overview.................................................................................................................................... 321 NIH Guidelines.......................................................................................................................... 321 NIH Databases........................................................................................................................... 323 Other Commercial Databases..................................................................................................... 325 The Genome Project and Crohn’s Disease ................................................................................. 325 APPENDIX B. PATIENT RESOURCES ............................................................................................... 329 Overview.................................................................................................................................... 329 Patient Guideline Sources.......................................................................................................... 329 Associations and Crohn’s Disease.............................................................................................. 336 Finding Associations.................................................................................................................. 340 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 343 Overview.................................................................................................................................... 343 Preparation................................................................................................................................. 343 Finding a Local Medical Library................................................................................................ 343 Medical Libraries in the U.S. and Canada ................................................................................. 343 ONLINE GLOSSARIES................................................................................................................ 349 Online Dictionary Directories ................................................................................................... 353 CROHN’S DISEASE DICTIONARY.......................................................................................... 355 INDEX .............................................................................................................................................. 427

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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 Crohn’s disease 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 Crohn’s disease, 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 Crohn’s disease, 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 Crohn’s disease. 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 Crohn’s disease, 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 Crohn’s disease. 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 CROHN’S DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Crohn’s disease.

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

Genes, Microbes, and T Cells: New Therapeutic Targets in Crohn's Disease Source: New England Journal of Medicine. 346(8): 614-616. February 21, 2002. Summary: Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease, are complex disorders with immunologic, environmental, and genetic components, each of which is the subject of intense investigation. This article reviews research that is focusing on genes, microbes, and T cells as new therapeutic targets in Crohn's disease. The author notes that research is providing theoretical bases for new approaches to therapy. One approach is to inhibit mucosal effector T cells. This is the most likely target of antibodies against TNF-alpha (tumor necrosis factor alpha), which have already been demonstrated to be effective in Crohn's disease; other agents are being tested. Another approach is the stimulation of regulatory T cells that inhibit mucosal effector T cells. Others include the restoration of the normal

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function of epithelium (the lining of the intestinal tract) with biologic factors and the alteration of the bacterial flora with probiotics or with microbes that are genetically engineered to inhibit the immune or inflammatory responses. 1 figure. 6 references. •

Critical Approach to New Forms of Treatment of Crohn's Disease and Ulcerative Colitis Source: Alimentary Pharmacology and Therapeutics. 16 (Supplement 4): 53-58. July 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: Most patient with inflammatory bowel disease (IBD) can be managed with conventional immunosuppressive therapy. However, the recent increase in knowledge of inflammatory mechanisms and the high incidence of toxicity with prolonged steroid use, together with the fact that controlled trials have clearly shown that glucocorticosteroids do not maintain remission, warrants a rational approach to the choice of newer and less well tested therapeutic approaches in those patients who are not responding effectively to the standard treatment. In this review article, the authors offer a critical approach to the newer forms of treatment in the management of severe cases of IBD. 45 references.

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Management of Refractory Crohn's Disease Source: Alimentary Pharmacology and Therapeutics. 16 (Supplement 4): 40-47. July 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 discusses resistance to conventional therapy, a common and intriguing problem in Crohn's disease patients. At the present time there is no agreement on its definition and several mechanisms are involved in its determination. Immunosuppressant agents, such as azathioprine (AZA), 6 mercaptopurine (6MP) and methotrexate (MTX) are effective drugs for controlling the inflammatory process and their use avoids chronic glucocorticosteroid treatment and its related side effects. Recently, the introduction of tumor necrosis factor (TNF) antibodies (infliximab) has dramatically changed the natural history of Crohn's disease and its therapeutic approach. Several studies have determined the effectiveness, mechanisms and safety of infliximab. However, this molecular approach has also left several questions unanswered about the mechanisms of refractoriness, possible concomitant treatments, and long term safety and efficacy. 51 references.

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Monitoring the Activity of Crohn's Disease Source: Alimentary Pharmacology and Therapeutics. 16 (Supplement 4): 29-33. July 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.

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Summary: Crohn's disease is characterized by a chronic inflammation of the intestine of unknown etiology. One of the main problems when treating patients with Crohn's disease, is the identification of patients undergoing early clinical relapse, for timely treatment and the possible prevention of complications. This article reviews strategies for monitoring the activity of Crohn's disease. No subclinical markers are currently available that predict relapse during remission. Several parameters have been proposed for this purpose. Although none have proven useful, growing evidence suggests a possible benefit in the clinical management of Crohn's disease. Among these, the authors identify clinical behavior, the characteristics of the host, clinical activity, markers of intestinal inflammation, and markers of immune activation. The authors conclude that their observations suggest that a persistent local immune activation during remission may represent a marker of early clinical relapse of Crohn's disease. 3 figures. 1 table. 26 references. •

Inflammatory Bowel Disease is Not Associated with an Increased Risk of Lymphoma Source: Gastroenterology. 121(5): 1080-1087. November 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Previous studies of the risk of lymphoma in inflammatory bowel disease (IBD) patients have provided conflicting results. This study examines the risk of Hodgkin's and non Hodgkin's lymphoma among patients with inflammatory bowel disease. The authors performed a retrospective cohort study using the General Practice Research Database. Inflammatory bowel disease patients were matched to randomly selected controls on age, sex, and primary care practice. Lymphoma rates were also compared with published age and sex specific rates. The study included 6,605 patients with Crohn's disease; 10,391 with ulcerative colitis (UC); and 60,506 controls followed for an average of 3.7, 3.9, and 4.4 years, respectively. The incidence of lymphoma was not increased in patients with IBD. In subgroup analyses, an increased risk was not observed among patients with Crohn's disease or UC. Compared with IBD patients not treated with azathioprine or 6MP, the relative risk of lymphoma among the 1,465 IBD patients treated with these medications was 1.27. The authors conclude that patients with IBD do not have an increased risk of lymphoma as compared with the general population. Although the authors cannot completely rule out a modest increased risk of lymphoma with azathioprine of 6MP therapy, an increased risk was not observed in this cohort. 4 tables. 48 references.

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Epidemiology and the Natural Course of Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 255-281. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory disorders of the gastrointestinal tract that are distributed unevenly within populations and throughout the world. This review article considers epidemiology and the natural course of inflammatory bowel disease (IBD). Although its exact causes remain unknown, epidemiology has provided insight into its pathogenesis. The authors examine geographic, ethnic, and other trends in IBD; risk factors (including genetic and environmental factors); and its natural history. The authors caution that performance of epidemiologic studies of IBD that are similar and easily compared has been hampered by lack of universally adopted diagnostic criteria for these disorders. A study from

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Baltimore has suggested that the incidence of IBD in African Americans is lower than in American whites. Studies of the incidence of IBD in populations that emigrate to high risk geographic areas suggest that the rate rises in these groups. Several studies have suggested that within a specified geographic area, the incidence of IBD is two to fourfold higher in Jews than in other ethnic groups. Several studies have found a trend toward increased rates of IBD in urban communities compared to rural ones. Both ulcerative colitis and Crohn disease are more frequent in high socioeconomic and white collar populations than in lower socioeconomic and blue collar populations. The authors review the extent and severity of disease, disease course, complications, cancer risks, survival (prognosis), and quality of life in UC and CD. The article concludes with a brief description of IBD in the pediatric population and in the elderly. 4 figures. 3 tables. 125 references. (AA-M). •

Medical Therapy for Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 297-321. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Despite advances in the understanding of Crohn's disease (CD) and ulcerative colitis (UC), the origins of inflammatory bowel disease (IBD) remain elusive. The therapeutic modalities used to treat CD and UC work at various sites along the immunoinflammatory cascades. This article reviews the pharmacology, mechanisms of action, clinical efficacy, and adverse effects of traditional therapies, such as aminosalicylates and corticosteroids, and examines the expanding number of immunomodulatory agents used in the management of IBD. Traditional therapies, such as aminosalicylates and corticosteroids, continue to be cornerstones in managing of IBD. However, immunomodulators, such as azathioprine and 6 mercaptopurine (6MP), are demonstrating increasing importance in the setting of steroid resistant and steroid dependent disease. Further, postoperative prophylaxis with certain antibiotics (e.g., metronidazole), aminosalicylates, or immunomodulators may be beneficial in preventing recurrence after resection in some patients with CD. In addition, immunosuppressive agents previously reserved for organ transplantation (e.g., cyclosporine) have expanded the number of medical therapies as advances in molecular engineering techniques are already heralding the development of a novel class of biologic therapies available for certain subgroups of patients. 5 tables. 252 references. (AA-M).

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Nutrition and Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 423-443. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article reviews the nutritional aspects of inflammatory bowel disease (IBD), including the mechanisms and manifestations of malnutrition and the efficacy of nutritional therapies. Nutrient deficiencies in patients with IBD occur via several mechanisms and may complicate the course of the disease. Up to 85 percent of patients hospitalized with exacerbations of IBD have protein energy malnutrition. This form of malnutrition also occurs between flareups of the disease, particularly in patients with Crohn's disease (CD), in whom the development of nutrient deficiencies is often insidious. Nutritional status is assessed by clinical examination and the use of nutritional indices such as the Subjective Global Assessment of nutritional status.

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Nutritional intervention may improve outcomes in certain people; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need parenteral nutrition. Clinical trials have established the efficacy of enteral formulations in nutritional repletion and reduction of disease activity in CD. Studies have shown the efficacy of nutrients with trophic effects, such as short chain fatty acids, glutamine, epidermal growth factor, nucleotides, and nutrients with immunomodulatory properties, such as omega 3 fatty acids and gamma linoleic acids, as therapy for IBD. 1 figure. 6 tables. 160 references. (AA-M). •

Hepatobiliary Manifestations of Inflammatory Bowel Disease Source: Gastroenterology Clinics of North America. 28(2): 491-513. June 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article reviews the hepatobiliary manifestations of inflammatory bowel disease (IBD). A large number of hepatobiliary abnormalities have been described in association with IBD, including primary sclerosing cholangitis (PSC), pericholangitis, chronic hepatitis, cryptogenic cirrhosis, cholangiocarcinoma (gallbladder cancer), and cholelithiasis (gallstones). PSC is the most common of these hepatobiliary diseases. This high degree of association with IBD suggests a common pathogenic mechanism; however, no causal relationship has been established. Medical therapy has not proven successful in slowing disease progression or prolonging survival. PSC usually progresses insidiously and eventually leads to cirrhosis. Endoscopic manipulation is recommended for treating complications of recurrent cholangitis or worsening jaundice in the setting of a dominant stricture, but endoscopic approaches have not been shown to improve survival or decrease the need for liver transplantation. Liver transplantation is life saving for patients with advanced PSC. Pericholangitis, gallstones, and chronic hepatitis are additional disorders noted in association with IBD, but they are much less common and easier to manage than PSC. 3 figures. 6 tables. 140 references. (AA-M).

Federally Funded Research on Crohn’s Disease The U.S. Government supports a variety of research studies relating to Crohn’s disease. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Crohn’s disease. 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 Crohn’s disease. The following is typical of the type of information found when searching the CRISP database for Crohn’s disease: 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: 5ASA REGULATION OF MNSOD IN INTESTINAL CELLS Principal Investigator & Institution: Valentine, John F.; Associate Professor; Medicine; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 30-APR-2003 Summary: Inflammatory bowel disease (ulcerative colitis and Crohn's disease) are chronic inflammatory disease of the gut for which there is no known cause or cure. It has been estimated that 2 million people in the United States have IBD. The peak onset of IBD is between 15 and 25 years of age and the majority of patients with IBD are under age 40. Mesalamine (5-ASA) is the active ingredient in sulfasalazine and is one of the major therapies use to treat active disease and for the maintenance of remission. The mechanism of action of 5-ASA remains unclear, however, we have found that 5-ASA induces a cytoprotective enzyme, manganese superoxide dismutase (MnSOD), at concentrations obtained in the colon of patients taking sulfasalazine orally. MnSOD is the only known 5-ASA regulated gene. The induction of MnSOD by 5-ASA may highlight a new therapeutic mechanism. MnSOD may serve a protective role in the bowel and prevent or reduce cytokine and oxygen radical mediated damage. This may be particularly important in the bowel as it contains low levels of antioxidants. The goal of this research project is to define the mechanisms that control the 5-ASA regulation of MnSOD gene expression in intestinal epithelial cells. The specific aims are designed to answer precise questions on the molecular mechanisms involved in the regulation of MnSOD gene expression by 5-ASA. In this proposal, we are using antisense MnSOD to document the role of MnSOD in 5-ASA induced cytoprotection in cell culture. We will determine how 5-ASA induces MnSOD by defining the sequences involved in the protein-DNA interactions that are responsible for the enhanced transcription of MnSOD. In addition to defining the cis-acting regulatory elements in the promoter region, we will identify and define enhancer elements involved in the regulation of MnSOD. Our studies will involve Dnase I hypersensitivity analysis, promoter deletion analysis, and evaluation of enhancer elements using transient transfection. Although the induction of MnSOD is transcriptional as determined by nuclear run-on experiments, we will also evaluate the role of MnSOD mRNA stabilization as a contributor to the induction of MnSOD mRNA levels. It is our premise that by understanding the mechanisms by which 5-ASA induces MnSOD, we will be able to identify and clone the transcription factors involved as well as design other therapeutic agents and 5-ASA derivatives to act as more potent inducers of MnSOD and possibly other yet to be defined 5-ASA regulated genes. By determining how therapeutic agents such as 5-ASA exert a beneficial influence on the disease activity of IBD, we may gain a further understanding of the pathogenesis of IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A GENETIC INSIGHT INTO UVEITIS Principal Investigator & Institution: Thompson, Mollie E.; Medicine; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This training award grant is submitted to enable Mollie Thompson MD to expand her basic science training so as to pursue a career studying the pathogenesis and treatment of uveitis. Dr. Thompson has been extensively trained as a clinician, with prior doctoral work in engineering and is committed to pursuing a research career in the molecular biology and genetics of inflammatory eye diseases. To attain the goal of becoming an independent contributor to the field of

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uveitis research, she has proposed a combination of graduate level classes and laboratory research under the guidance of Dr. James T. Rosenbaum. Dr. Rosenbaum is ideally suited for this role because of his combined position as director of the uveitis clinic and Chief of the Division of Arthritis and Rheumatic Diseases. He leads a respected team of uveitis researchers and has successfully mentored many other clinicians and scientists in the field. The Department of Medicine and the Casey Eye Institute have the resources required and provide a supportive environment for education and research. The research will utilize state of the art molecular techniques to investigate the role of the NOD2 gene in uveitis. One important clue to the pathogenesis of uveitis comes from the discovery of a gene associated with a rare form of familial granulomatous uveitis called Blau syndrome. Mutations in the NOD2 gene have been associated with Blau syndrome and with Crohn's disease, a granulomatous inflammatory disease of the intestine, eye and joints. This gene encodes for a protein that is important in regulating the innate immune response to intracellular bacteria, but its relationship to inflammatory eye disease is not understood. We propose to characterize the distribution and function of the NOD2 protein, and to determine how gene expression affects cellular response to intracellular bacterial infection. Monocyte cell lines transfected with wild-type and Blau mutated forms of NOD2 will be stimulated by bacterial endotoxin and by exposure to different strains of Salmonella bacteria. Expression of genes important in inflammation, the production of inflammatory cytokines, cellular apoptosis, and the induction of nuclear transcription factors critical in inflammation will be measured under conditions of bacterial challenge. The results will be important not only to the understanding of Blau syndrome but will also shed light on the general mechanisms producing immune-mediated inflammatory ocular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI CD40L THERAPY IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Blumberg, Richard S.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001 Summary: Inflammatory bowel diseases (IBD), categorized as Crohn's disease (CD) or ulcerative colitis (UC), are complex disorders of unknown etiology with a spectrum of clinical features which exhibit great variation among affected subjects. The majority of patients, however, will required immunosuppressive and/or immunomodulatory agents which are not universally successful in effective maintaining remission and preventing disease relapse. Recent insights into the basic mechanisms of immune responses and the extension of these concepts to CD and UC have led to the identification of new therapeutic targets which may be more efficacious in IBD therapy by focusing on critical biologic pathways. More recently, it has been suggested that costimulatory signals involved in antigen presentation appear to affect immune responses through the up- regulation of an accessory molecule named CD40 ligand (CD40L) on T cells. The interaction between the molecule CD40 and CD40L appears to play a role in CD4 T cell-mediated responses that characterize a variety of autoimmune-mediated disease states including inflammatory bowel disease. Based upon these biologic considerations of CD40-CD40L activity, we believe that human. IBD, both CD and UC, may be diseases which would benefit clinically from therapy directed at the CD40CD40L pathway. We therefore propose a clinical trial of a humanized anti- CD40L antibody in study subjects with inflammatory bowel disease with the following specific aims: 1) To determine any toxicity and potential benefit from anti-CD40L antibody

10 Crohn’s Disease

therapy in patients with steroid-resistant or refractory CD and UC. 2) To determine the incidence of clinical and histologic disease remission in patients with steroid-resistant or refractory CD and UC treated with anti-CD40L antibody therapy. 3) To determine the proportion of patients who remain in sustained clinical remission 12 months after antiCD40L antibody therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI TNF ALPHA ANTIBODY TO TREAT CROHN'S DISEASE Principal Investigator & Institution: Rodgers, Vance D.; Scripps Research Institute 10550 N Torrey Pines Rd San Diego, CA 92037 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AZATHIOPRINE /SULFASALAZINE /PENTASA INTERACTIONS IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Sandborn, William J.; Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001 Summary: A pharmacodynamic and pharmacokinetic study to determine the clinical significance of drug interactions between azathioprine and sulfasalazine, Balsalazide or Pentasa in patients with inflammatory bowel disease. The specific aims of the study are to estimate the proportion of clinically important leukopenia, defined as a total white blood cell (WBC) count <3,000 X 10 9/L, when SAS 4 g/day, Balsalazide 6.75 g/day, or Pentasa 4 g/day is combined with maintenance of remission treatment with a stable dose of 6MP or AZA in patients with one of the inflammatory bowel diseases (IBD), either ulcerative colitis (UC) or Crohn's disease. These estimates (and 95% CIs) will be computed at weeks 2, 4, 6, and 8 after adding SAS, Balsalazide, or Pentasa to AZA or 6MP therapy. The secondary aim is to estimate the change (and 95% CI) in total WBC count for each treatment group at weeks 2, 4, 6, and 8 after adding SAS, Balsalazide, or Pentasa to AZA or 6MP therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AZATHIOPRINE LOADING TO DECREASE RESPONSE TIME IN CROHN'S DISEASE Principal Investigator & Institution: Isaacs, Kim L.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BACTERIAL INDUCED COLITIS IN HLA-B27 RATS Principal Investigator & Institution: Dieleman, Levinus A.; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 10-MAY-1998; Project End 30-NOV-2002 Summary: (taken from application) Genetic and environmental factors are extremely important in the pathogenesis of the idiopathic chronic inflammatory bowel diseases

Studies 11

(IBD), ulcerative colitis (UC) and Crohn's disease (CD). New rodent models of chronic intestinal inflammation have contributed substantially to our knowledge of the pathogenesis of IBD. One better characterized model is HLA-B27 transgenic rats, in which the overexpression of the gene for the MHC class I molecule HLA-B27 leads to the spontaneous development of colitis, gastroduodenitis, peripheral arthritis and spondylitis. Our hypothesis is that chronic colitis and gastritis is the result of an overly aggressive immune response to luminal bacteria in a genetically susceptible host. This T Iymphocyte-dominated immune response to specific luminal bacteria is regulated by antigen presenting cells (APC). This hypothesis will be evaluated in HLA-B27 transgenic rats, which develop progressive colitis, gastritis and arthritis when raised in specific pathogen-free environment or when colonized with Bacteroides vulgatus, but which have no clinical or histological disease when raised in a sterile environment or monoassociated with E. coli. However, the immunological mechanisms determining how these bacteria initiate and perpetuate a chronic immune response need to elucidated. The unraveling of these mechanisms will answer several fundamental questions concerning the pathogenesis of chronic inflammatory bowel diseases. We will address several fundamental questions of IBD pathogenesis in the following specific aims: 1) Determine which bacterial components induce gastrointestinal inflammation and conversely, whether certain resident luminal bacteria can prevent this inflammation. 2) Define the mechanisms by which T lymphocytes induce or prevent gastrointestinal inflammation. Successful completion of these specific aims will not only provide essential insights into the pathogenesis of experimental intestinal inflammation, but will also reveal pathogenetic mechanisms of IBD and suggest novel therapeutic approaches targeting etiologic mechanisms. This MD/PhD has considerable experience with various studies on the role of cytokines in several murine models of acute and chronic intestinal inflammation. The research project for this grant will enable the candidate to expand his knowledge in new areas of cellular immunology and gnotobiotic technology, which will be complemented by formal immunology/microbiology courses. This training experience will take place in a Digestive Disease Center focused on inflammation and fibrosis under the sponsorship of experts in animal studies, gnotobiotic research and cellular immunology. This expertise will foster the development of an independent investigator with skills in both clinical and basic science. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BACTERIAL INFLAMMATION

MODULATION

OF

GASTROINTESTINAL

Principal Investigator & Institution: Czinn, Steven J.; Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Inflammatory bowel disease is a general term used to describe a group of chronic inflammatory disorders of the gastrointestinal tract. The two major clinical entities are ulcerative colitis and Crohn's disease. The two major clinical entities are ulcerative colitis and Crohn's disease. Clinically ulcerative colitis is confined to the large intestine, whereas Crohn's disease may affect any part of the gastrointestinal tract. The Crohn'S & Colitis Foundation of America estimates that about two million Americans suffer from inflammatory bowel disease, 300,000 of them in the pediatric age group. Despite traditional medical therapy, inflammatory bowel disease in children results in significant morbidity such as chronic abdominal pain, rectal bleeding, anemia, weight loss and growth stunt. While active investigation has yet to discover what causes

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inflammatory bowel disease, it is believed than an inappropriate host immune response to antigens (bacteria or flood) normally found in the gastrointestinal tract results in a state of chronic inflammation. It has been difficult to investigate the relationship between luminal bacteria and immune dysregulation due to the lack of a colitis model induced by a single well-defined organism. Infection of the normally abiotic mouse stomach with Helicobacter and Lactobacillus species provides an excellent model for the investigation of bacteria-associated chronic inflammation of the gastrointestinal mucosa. We have developed several murine models in which various bacterial species, that are either normally non pathogenic or are only mildly pathogenic, can induce a state of chronic mucosal inflammation. The inflammatory response can be generated either by deleting or adding various immunoregulatory cytokines, or by systemically immunizing mice prior to infection. Of particular importance is the observation that the mucosal inflammation is maintained even when organisms are no longer detectable by microbiological and molecular techniques. Using these models we will test the central hypotheses that chronic gastrointestinal inflammation results from an aberrant immune response to antigenic stimulus, consisting of normal gastrointestinal bacteria. We propose to investigate the relationship between mucosal bacteria and immune regulation in the early, intermediate and late stages of chronic mucosal inflammation using our unique models of gastric Helicobacter and Lactobacillus infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEHAVIORAL RX & NUTRITION IN PEDIATRIC CHRONIC DISEASE Principal Investigator & Institution: Stark, Lori J.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (adapted from the application) Specific Aims of this mid-career patientoriented research award are 1) to further the candidate’s independent patient-oriented clinical research program in behavioral interventions for enhancing children’s growth and nutritional status, and 2) to provide the candidate protected time and resources necessary to mentor junior faculty and trainees pursuing clinical investigation in behavioral nutrition interventions for children. The Candidate’s programmatic research has focused on examining behavioral factors affecting adherence to dietary recommendations and designing and testing behavioral interventions to enhance dietary adherence in children with chronic medical conditions. Currently, the candidate has two funded grants on improving nutritional status in children with cystic fibrosis and juvenile rheumatoid arthritis. The candidate also has an established record of providing mentorship to postdoctoral fellows and junior faculty. The Training Plan will permit the candidate to enhance her multi-disciplinary research in pediatric nutrition by the acquisition of knowledge and skills for the measurement of nutrient intake, nutrient requirements, growth, and body composition. This will complement her skills in the design of behavioral interventions to promote optimal growth pattern and nutrition status in children in her own research and in that of junior faculty and fellows who she mentors. The Research Plan will expand the candidate’s ongoing research examining the application of a behavioral intervention to increase calcium intake and bone mineral density in children with Crohn’s disease. The Mentoring Plan for junior faculty and postdoctoral fellows will consist of 1) individualized mentoring of 4 junior faculty; 2) intensive practical training in patient-oriented research within the context of the current research plan for 1 to 2 postdoctoral fellows per year; 3) training of junior faculty and

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fellows by candidate on the integration of assessment methodologies of nutrient intake, growth, and body composition into behavioral methodologies for assessment and intervention in pediatric care; and 4) participation of junior faculty and postdoctoral fellows in established didactic programs on manuscript and grant writing, design of clinical trails and clinical research methodology, and ethics in clinical research. Children’s Hospital Medical Center and the University of Cincinnati College of Medicine provide an ideal setting for this award because of the commitment to patientoriented research, the presence of a strong pediatric General Clinical Research Center, and the institution of new initiatives to promote innovative clinical research including submission of a Clinical Research Curriculum Award (K30). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLOOD BASED IBD DIAGNOSIS USING MICROARRAY GENE PROFILES Principal Investigator & Institution: Dervieux, Thierry; Prometheus Laboratories, Inc. 5739 Pacific Center Blvd San Diego, CA 921214203 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) has been the focus of an intense research effort to improve diagnostic accuracy, shorten the time to confirmed diagnosis, identify new therapeutic agents, and predict responses to therapeutic agents. Inflammatory bowel disease (IBD) continues to present monumental challenges to the basic understanding of the onset and control of inflammatory processes. However, the new science of microarray gene expression profiling provides an incomparably powerful technique to 1. identify the molecular participants of the inflammatory process and 2. differentiate the mechanisms of these IBD diseases at the molecular level. Microarray technology allows the simultaneous study of thousands of expressed genes and the comparison of diseased versus control gene expression profiles. The goal of this project is to apply microarray gene expression technology to patient matched peripheral blood and biopsy samples and directly compare over-expressed and under-expressed genes in CD and UC versus non-IBD controls. From the thousands of genes studied, this project seeks to identify a very small number of genes (a Focused Gene Expression Profile) that will allow development of an accurate, non-invasive blood test for IBD diagnosis and definitive stratification of Crohn's disease and ulcerative colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BONE MINERAL DENSITY IN YOUTH WITH CROHN'S DISEASE Principal Investigator & Institution: Semeao, Edisio; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CA KINETICS IN PREADOLESCENT/ADOLESCENT GIRLS W /CROHN'S Principal Investigator & Institution: Caballero, Benjamin H.; Director and Professor; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001

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Summary: Background & Aims: Children with Crohn's disease are at risk for osteoporosis because of undernutrition, prolonged corticosteroid therapy, inflammatory process itself, inadequate calcium intake or absorption and vitamin D deficiency. The aim of this study is to address the effects of Crohn's disease and cumulative corticosteroid dose on calcium metabolism, efficiency of calcium absorption, calcitropic hormone levels and bone mineral density in preadolescent and adolescent girls. Methods: Seven female subjects (12 to 1 yrs. of age) have been enrolled. Patients are undergoing anthropometric assessment, pubertal staging, bone age radiography, and BMD assessment by dual energy 2-ray absorptiometry (DEXA) of the lumbar spine and total body. Clinical disease activity of CD is assessing by te Pediartic Crohn's Disease Activity Index (PCDAI). The cumulative corticosteroid dose (i grams) is calculating. Laboratory evaluations include serum levels of albumin, prealbumin, ionized Ca, phosphated, alkaline phosphatase, 25-hydroxyvitamin D [25-OHD], 1,25dihydroxyvitamin D [1,25-(OH)xD], calcitonin, parathyroid hormone (PTH), estradiol, osteocalcin and interleukin-6, and urinary levels of N-telopeptide. We are measuring calcium absorption and urinary calcium excretion, using a dual-tracer, stable-isotope technique and thermal ionization mass spectrometry. Results: We have not completed this study yet. We hypothesize that the low bone mineral density reported in girls with Crohn's disease is related to disturbances in calcium metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CD11B/CD18 AND NEUTROPHIL EPITHELIAL INTERACTIONS Principal Investigator & Institution: Parkos, Charles A.; Associate Professor, Director; Pathology; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 05-APR-1995; Project End 29-FEB-2004 Summary: Many inflammatory diseases of mucosal surfaces are characterized by transepithelial migration of neutrophils (PMN). Examples of such diseases are common in the gastrointestinal system (ulcerative colitis, Crohn's disease), respiratory tract (bronchial pneumonia, bronchitis), and urinary tract (pyelonephritis, cystitis). Accumulation of neutrophils within the lumenal spaces of these organs is associated with epithelial injury and correlates with disease symptoms. Despite a wealth of evidence supporting a central role of PMN in epithelial dysfunction in these diseases, the mechanism(s) of leukocyte interaction with mucosal remains poorly defined. In this proposal, our studies will focus on defining the molecular basis of leukocyte interactions with epithelial cells. Previously, we have shown that PMN transepithelial migration requires specific regions of the neutrophil beta2 integrin CD11b/CD18 and is independent of selectins and ICAM-1. Furthermore, we identified CD47 as an additional crucial component of the transepithelial migration response. However, the precise molecular details of these adhesive events and the nature of the epithelial counterreceptors for migrating PMN remain undefined. The overall goals of this proposal are to identify and characterize key adhesive interactions between neutrophils (PMN) and epithelial cells that serve to regulate the process of PMN transepithelial migration. Recently, a novel immunoglobulin superfamily member termed junction adhesion molecule (JAM) that is concentrated at cell-to-cell borders (intercellular junctions) of murine endothelium and epithelium was shown to participate in monocyte transmigration across mouse endothelium. In Specific Aim 1, we will extend our primary characterizing of the human homolog of JAM to define its role in PMN interactions with epithelial cells. In Specific aim 2, we will define the mechanism of how a novel epithelial mAb inhibits PMN migration and continue to produce others that inhibit the PMN transmigration response. Specific aim 3 will focus on the identification

Studies 15

of specific epithelial receptors for CD11b/CD18 using monoclonal antibodies. Lastly, Specific aim 4 will employ random peptide phage display to identify peptide ligands for CFD11b/CD18 that modulate PMN-epithelial adhesion, Information from these studies will lead to a better understanding of the molecular events involved in PMN interactions with epithelial cells and may provide new ideas for therapeutic strategies aimed at attenuating inflammatory diseases of mucosal surfaces. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CD1D EXPRESSION BY INTESTINAL EPITHELIAL CELLS Principal Investigator & Institution: Page, Michael J.; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, PA 17033 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CELL ADHESION & TRAFFICKING IN EXPERIMENTAL ILEITIS Principal Investigator & Institution: Ley, Klaus F.; Professor of Biomed Eng., Mol Phys & Bio; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001 Summary: Selectins, selectin ligands, integrins, and immunoglobulin-like adhesion molecules are critically involved in leukocyte-endothelial adhesion in inflammation, leukocyte-platelet interactions, and lymphocyte trafficking. Emigration of neutrophils and lymphocytes is preceded by rolling, which is largely mediated by selectins alpha4beta7 integrin and L-selectin are necessary to direct lymphocyte homing to Peyer's patches and other gut- associated lymphatic tissues. P- and E-selectins are rapidly up-regulated on the endothelial surface upon exposure to inflammatory stimuli and are involved in neutrophil and monocyte recruitment and homing on T helper 1 (Th1)-like lymphocytes. Beta2 integrins (CD18) are expressed on the leukocyte surface and are involved in leukocyte adhesion molecules in leukocyte recruitment and tissue damage in a spontaneous mouse model of Crohn's disease (CD), the SAMP1/Yit mouse. We hypothesize that (1) these mice express adhesion molecules relevant to the trafficking of T lymphocytes, neutrophils, and other leukocytes; (2) leukocyte and/or endothelial adhesion molecules are required for development of inflammatory disease in immunodeficient mice adaptively transferred with CD4+ T cells from SAMP1/Yit mice; and (3) CD4+ T lymphocytes use specific adhesion molecules to home to the terminal ileum of mice and cause disease in this model. Methods include the use of transgenic and knockout mice, intravital microscopy, tissue histology, immunohistochemistry, flow cytometry, measurement of soluble adhesion molecules, and lymphocyte homing assays. Adoptive transfer of SAMP1/Yit CD4+ T cells will be used to produce CD-like disease in immunodeficient (RAG-2 -/-) mice and in adhesion molecule-deficient mice back-crossed into the RAG-2 -/- mutation. Project 4 is aimed to identifying the molecular mechanisms of lymphocyte homing and inflammatory cell recruitment to CD lesions in vivo. Insights into the mechanisms of T lymphocyte homing and inflammatory cell recruitment will provide a rationale for clinical studies investigating the efficacy of interventions aimed at modulating the expression and/or function of leukocyte-endothelial adhesion molecules. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CENTER FOR THE STUDY OF INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Podolsky, Daniel K.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 05-FEB-1991; Project End 31-DEC-2005 Summary: (Adapted from the application) The Center for the Study of Inflammatory Bowel Disease (CSIBD) is a multidisciplinary program to define fundamental mechanisms underlying Crohn’s disease and ulcerative colitis. This Center encompasses sixty-seven investigators at the Massachusetts General Hospital (MGH) and allied institutions pursuing research in a broad spectrum of basic science relevant to IBD. Since its formation eight years ago, the CSIBD has served as a vehicle to achieve advances in our understanding of these diseases through the study of relevant basic biological processes and the directed study of the diseases themselves. The research program of this Center is organized around the central hypothesis that IBD results from activation by luminal antigens (dietary or microbial in origin) of an upregulated chronic immune response due to genetically determined alterations of epithelial cell or immune function including, a lack of appropriate downregulatory functions. Major advances made possible by the CSIBD in the nine years since its inception include the development and characterization of new genetic mouse models of IBD, delineation of mechanisms of lymphocyte activation and leukocyte recruitment to sites of inflammation, identification of key peptides involved in sustaining mucosal integrity, characterization of the mechanisms of mucosal healing following injury, and improved understanding of the regulation of mucosal immune responses and the complex network of regulatory peptides (cytokines) that modulate mucosal immune and epithelial cell function. Over the next five years, the CSIBD will promote further progress in the study of basic aspects of mucosal biology with translation to the study and treatment of IBD using the tools of molecular and cellular biology. A major focus of CSIBD research in the next five years will be the coordinated multi-disciplinary study of mechanisms leading to chronic intestinal inflammation in the available murine genetic models of "IBD". Experiments will delineate interactions between environmental factors and different genetic loci. The overall goal of advancing our knowledge of IBD will continue to be carried out through five Biomedical Cores. These include Molecular Biology, Morphology and Immunology Cores to provide access to advanced technologies. The Genetic Animal Models and Clinical/Tissue Cores will provide access to relevant animal models and patient tissues for study. In addition to advancing the understanding of IBD per se, the goals of this Center will continue to include the recruitment of established investigators to the study of IBD, enhancing collaboration among Center investigators and encouraging the development of young investigators committed to pursuing IBD research. These goals are fostered by Pilot/Feasibility Study awards which support new research initiatives as well as an enrichment program of seminars, workshops and symposia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COREGULATORY MODEL OF SMOOTH MUSCLE MYOGENESIS Principal Investigator & Institution: Mchugh, Kirk M.; Pathology, Anat/Cell Biology; Thomas Jefferson University Office of Research Administration Philadelphia, PA 191075587 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: Mature gastrointestinal (GI) smooth muscle cells (SMCs) possess a high degree of developmental plasticity retaining the ability to interconvert between

Studies 17

proliferative and differentiated states in response to external stimuli. Dysregulation of GI SMC differentiation is associated with a variety of GI disorders including Hirschsprung's disease, Crohn's disease, ulcerative colitis, motility disorders, and GI smooth muscle tumors. The goal of this proposal is to gain a better understanding of the molecular mechanisms controlling GI smooth muscle development. Our hypothesis is that GI smooth muscle myogenesis is controlled by the synergistic expression of transcription factors that are common to all muscle lineages, as well as those that are smooth muscle specific. This hypothesis is supported by recent data from our lab identifying a key regulatory complex within the gamma-smooth muscle isoactin gene promoter. Interconversion between proliferative and differentiated GI SMC phenotypes involves differential binding of serum response factor (SRF), distinct isotypes of MEF2, and additional unidentified transcription factors to this critical regulatory complex. Utilization of these same transcription factors by this complex is altered in G1 smooth muscle tumors and ulcerative colitis suggesting that SRF and MEF2 may play a role in GI smooth muscle pathogenesis. We plan to identify the key transcription factors involved in GI smooth muscle myogenesis by elucidating the factors controlling gamma-smooth muscle isoactin gene expression in primary cultures of GI SMCs. We will use a unique, mass-arrayed screening technique to isolate and identify novel GI smooth muscle-specific transcription factors. Cultured GI SMCs will be used to assess the functional role that SRF, MEF2, and novel transcription factors play in modulating GI SMC differentiation. Identifying the key transcription factors involved in GI smooth muscle myogenesis, and determining how they interact to modulate GI SMC phenotype is critical to gaining a better understanding of GI smooth muscle pathogenesis in a variety of GI diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TRANSGENIC AND CHIMERIC MOUSE FACILITY Principal Investigator & Institution: Cooke, Nancy E.; Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2007 Summary: The generation of transgenic mice through the introduction of foreign DNA into the fertilized mouse oocyte (1), has resulted in the development of an exciting array of new in vivo experimental models for the study of development, genetic disorders, transcriptional control of gene expression, tissue specificity of gene expression, and oncogenesis. For genes normally expressed in cells without adequate tissue culture counterparts, the generation of transgenic animals is the best current means of localizing gene control elements and studying gene functions (2). Additional techniques such as targeted oncogenesis (3), targeted ablation of cell linkages in the developing mouse (4,5), binary systems for regulating transgene expression (6), and homologous recombination using the Cre and loxP system from bacteriophage P1 (7) are refining the applications of transgenic technology. Gene-targeted (8,9) and transgenic mouse models have had a major impact on the understanding of many aspects of liver and digestive disorders. For example, an increased understanding of the enteric nervous system and insights into the pathophysiology of a ganglionic megacolon of Hirschspring's disease have accrued based upon the analysis of a varies of transgenic mouse models. These include mice with targeted disruptions of endothelin-3 or its receptor endothelin B, the tyrosine kinase RET and glial cell line-derived neurotrophic factor. These studies have led to the concept that at least two different mechanisms can cause aganglionosis of the terminal bowel (10). Similarly, deficiency of neuronal nitric oxide synthetase (nNOS) has been shown to induce to gastric dilatration and stasis in mice (11). Over-expression and

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deficiency of gastrin have been developed in transgenic mice confirming gastrin's role as a key regulator of parietal cell function, but also pointing to additional, unexpected functions such as colonic proliferation (12, 13). Experimental mouse models of immune imbalance leading to intestinal inflammation such as with the interleukin-10 null mice (14) or TNF over-expressing mice (15) begin to provide mouse models for inflammatory bowel diseases such as Crohn's disease. Intestinal epithelial apoptosis can be studied in transgenic mouse models such as p53 null mice, but not in tissue culture models (16). Studies of transgenic mouse lines have contributed to an understanding of the mechanisms involved in the initiation of liver regeneration and have provided critical information about the gene regulation and function of many liver- expressed genes (17). It is clear that the complexity of the digestive organs is well suited to physiologic analysis in transgenic and targeted mouse models. The primary function of the Transgenic and Chimeric Mouse Facility is to provide a centralized laboratory that will generate infection-free, transgenic founder or chimeric strains of mice carrying transgenes or gene knock-outs of specific interest to individual projects in the Center. The centralization of these technically demanding procedures results in enhanced efficiency and cost reduction for reach project. The generation of mouse models facilitates collaborations and interactions among the Center members as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COX GENE REGULATION IN INTESTINAL MYOFIBROBLASTS Principal Investigator & Institution: Powell, Don W.; Professor of Medicine; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The general hypothesis of this grant proposal is that intestinal subepithelial myofibroblasts (ISEMF) are the source of soluble factors that modulate epithelial growth, differentiation, and repair and play a pivotal role in mucosal immunophysiology and cancer. Located at the interface between the epithelium and lamina propria, ISEMF modulate information transfer between these tissue compartments. Through elaboration of basement membrane components, prostaglandins (PGs). and growth factors, ISEMF modulate processes of epithelial cell growth, differentiation, and wound repair. One major pathway by which ISEMF influence epithelial and lamina propria cells is through the production of PGs by cyclooxygenase-2 (COX-2). Data indicate that the bulk of mucosal PG synthesis occurs in the lamina propria, possibly in ISEMF. Because COX-2 regulation appears to be different in the various cell types thus far studied, this proposed research will test the hypothesis that ISEMF are major sites of COX-2 expression and that pro- and antiinflammatory agents act in part by inducing or inhibiting COX-2 expression in ISEMF. Specific Aims: 1. Determine the mechanisms by which proinflammatory cytokines (IFN-gamma, TNFalpha, IL-1) and eicosanoids (arachidonic acid, various HETEs) induce COX-2 gene expression in ISEMF, 2. Analyze the mechanisms responsible for inhibition of COX-2 gene expression in ISEMF by antiinflammatory cytokines (IL-4, IL-13) and therapeutic corticosteroids, and 3. Characterize COX-2 expression in human ISEMF in situ and in primary ISEMF cultures from normal small intestine and colon and from various inflammatory diseases such as ulcerative colitis, Crohn's disease, and collagenous colitis and various neoplastic states such as adenomatous and hamartomatous polyps and both sporadic and familial adenomatous polyposis colon cancers. We will use an ISEMF cell line (18Co) isolated from human colon, reporter gene constructs containing full length and mutant COX-2 regulatory elements, gel shift assays, in vitro and in vivo promoter

Studies 19

footprinting to determine the role of NF-kappaB/cRel, cEBP/NF-IL6, CREB/ATF, and other transcription factors in the induction and inhibition of COX-2 expression in ISEMF. Key findings from studies with 18Co will be confirmed in primary cultures of ISEMF from normal and various disease states. Using immunohistocytochemistry and in situ hybridization techniques we will identify the cellular sites of COX-2 gene expression in normal and diseased tissue and thus shed light on the role of ISEMF in gastrointestinal disease. These studies should define the processes which mediate signalling between intestinal subepithelial myofibroblasts and other immune and nonimmune cells, and how these processes are disrupted in pathological states such as IBD, fibrotic disorders, and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CROHNS DISEASE AND OSTEOPENIA--BASIC PATHOGENIC MECHANISMS Principal Investigator & Institution: Sylvester, Francisco; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CROHN'S DISEASE GENE MAPPING OF CHROMOSOME 16 Principal Investigator & Institution: Brant, Steven R.; Professor of Gastroenterology; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: Evidence from identical twin studies, familial aggregation, and consistently greater risk in Ashkenazim has shown that the greatest risk for developing Crohn's disease (CD) is genetic. A CD locus on chromosome 16, IBD1, was identified in 1996. IBD1 is the most consistently demonstrated inflammatory bowel disease (IBD) genetic locus, replicated in five out of seven studies. As part of an International IBD Genetics Consortium, we have recently provided definitive evidence for the IBD1 locus. Genotyping of 372 fully informative CD pedigrees randomly selected from 12 international IBD collaborators provided highly significant evidence for IBD1 (Lod 6.41). There was no evidence for IBD1 in 242 UC or mixed pedigrees. IBD1 appears to be particularly relevant in Asheknazim pedigrees. We recently found that stratifying pedigrees by early age at diagnosis and greater disease severity may greatly reduce linkage heterogeneity for IBD1. The overall goal of this application is to identify genetic mutations or polymorphisms responsible for IBD1. This goal will be achieved by the following specific aims: (1) we will identify linkage disequilibrium for IBD1 in Ashkenazim pedigrees. We will genotype markers spaced an average of 100 kb apart in 120 Ashkenazim trios with early-onset, severe CD. (2) For markers where there is evidence for linkage disequilibrium, we will extend evidence for the immediate region by genotyping adjacent markers, additional Ashkenazim CD pedigrees and nonAshkenazim pedigrees ultimately identifying a minimal IBDI haplotype with maximal evidence of linkage disequilibrium. (3) We will perform mutation/polymorphism analysis on prioritized genes that map within this haplotype, and determine, using linkage disequilibrium analytic methods, which genetic variation is responsible for the genetic risk of Crohn's disease associated with the IBD1, chromosome 16 locus. Defining the IBD1 mutation for CD will be a major step in unraveling the etiology and

20 Crohn’s Disease

pathophysiology of this enigmatic disease, improve genetic counseling and make possible novel preventative and therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CROHN'S DISEASE: MICROFLORA ANALYSIS AND HOST RESPONSE Principal Investigator & Institution: Relman, David A.; Assistant Professor; Microbiology and Immunology; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): The long-term objectives of this application are to identify microorganisms as well as human cellular pathways that promote Crohn’s disease, and to develop novel diagnostic tools and therapeutic strategies for this disease. The short-term objectives include the identification of microflora and host expression patterns that are associated with disease activity, and assessment of molecular methods for pathogen identification. The specific aims are: Aim 1: Identify bacterial and archaeal species associated with active Crohn’s disease using broad range ribosomal DNA PCR, laser capture microdissection, and fluorescent in situ hybridization. Tissues with ulcerative colitis, inactive Crohn’s disease, and no apparent disease will serve as some of the controls. Aim 2: Quantify differences in relative abundance of bacterial and archaeal species found in Crohn’s disease and controls. An rDNA microarray will be used, as well as a more traditional slot-blot hybridization approach. Aim 3: Identify global host gene expression patterns in intestinal tissue and peripheral blood that are associated with Crohn’s disease. Expression patterns will be defined that correlate with disease state and activity, and with bacterial and archaeal microflora profiles. State of the art, high-density human cDNA microarrays, and both unsupervised and supervised pattern recognition algorithms will be used to reveal disease-associated signatures. This combination of approaches offers opportunities for characterizing Crohn’s disease, and for examining the complex interactions of human host and microbial flora during states of health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOKINE TRAFFICKING AND SECRETION IN MACROPHAGES Principal Investigator & Institution: Stow, Jennifer L.; University of Queensland Cumbrae Stewart Building Brisbane, Queensland, 4072 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Tumour necrosis factor alpha (TNFalpha) is a proinflammatory, clinically-important cytokine secreted by activated macrophages. TNFalpha has widespread roles in host defence, tumour ceil killing and homeostasis. However, excess secretion of TNFa is a major cause of tissue damage in chronic inflammatory diseases such as Crohn's disease, arthritis and in cancer. Cytokine secretion in macrophages is poorly understood at the molecular and cellular level. The goal of these studies is to generate an understanding of how TNFalpha is trafficked to the cell surface for secretion by macrophages. Recent findings have revealed a specific tSNARE, (Syntaxin4/SNAP-23/Munc18c), a vesicle docking and fusion complex, as a key regulator of TNFa trafficking in macrophages. The proposed studies will further investigate t-SNARE expression and function in macrophages and in inflammation. The studies have three specific aims. First, to address how SNARE proteins are regulated in macrophages. LPS-responsive transcriptional and post-translational mechanisms will be studied at the level of gene and protein regulation using microarrays, then defining

Studies 21

changes in protein modifications. Secondly, in vitro and in vivo approaches will be used to explore the function of Syntaxin4 as a rate-limiting 'rheostat' for TNFalpha secretion. Syntaxin4 levels will be titrated by expression of wild type or mutant cDNAs in cells and in transgenic mice. A mouse model will be used to investigate the roles of macrophages, TNFalpha and Syntaxin4 in inflammatory bowel disease. The third aim uses a combination of techniques -fluorescence imaging in live cells, immunolabeling and proteomics - to characterize the TNFalpha transport vesicles and secretory pathways in macrophages. Taken together this work will generate important insights into the pathobiology of macrophages and TNFalpha. Defining the function of the Syntaxin4 t-SNARE in macrophages will be a major advance in understanding trafficking. Finally, trafficking proteins - in particular Syntaxin4 - offer potential as drug targets for novel anti-TNFalpha therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNA MICROARRAY FOR GASTROENTEROLOGY RESEARCH Principal Investigator & Institution: Curto, Ernest V.; Integriderm, Llc. 2800 Milan Ct Birmingham, AL 35211 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-OCT-2002 Summary: We propose to create a highly informative DNA microarray specifically for gastrointestinal (GI) research with an emphasis on genes associated with inflammatory bowel disease (IBD). RNAs will be harvested from pertinent GI tissues and cell types and screened for genes of high differential expression ("signature biomarker genes") utilizing currently available human DNA microarrays. Gene expression of GI tissues will be profiled against available sequence-validated human cDNAs (ca. 40,000). The 4400 most differentially expressed genes will be selected for inclusion on the array, providing an eight-to-ten fold enrichment of important genes over housekeeping genes. From the selected set of genes we will choose a very informative subset of 384 genes to be triplicated on the array. This triplicate subset will provide statistical validation for what we believe will be some of the most important genes in GI research. Our patentpending method will drive the selection criteria with a bias toward those genes deemed of particular interest to gastroenterology researchers. The GI array will provide researchers with a cost-effective tool to study gene expression in GI tissues. PROPOSED COMMERCIAL APPLICATIONS: The success of the human genome project has sparked growing interest into the genetics of the GI tract. Our GI array will fill a niche in this market, providing a highly informative and cost effective DNA array for researchers eager to pursue this new technology to develop new clinical diagnostics and in vitro assays for drug therapies. This timely product will complement our best selling dermatology array DermArray(TM). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DO RELATIVES OF CROHN'S DISEASE PATIENTS HAVE SILENT CROHN'S DISEASE? Principal Investigator & Institution: Katz, Jeffry A.; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: The goal of this clinical investigation is to determine whether first-degree relatives of patients with Crohn's disease have clinically silent intestinal inflammation. The central hypothesis of this study is that a proportion of first-degree relatives of patients with Crohn's disease manifest histologic and immunologic evidence of

22 Crohn’s Disease

intestinal inflammation in the absence of clinical symptoms. This hypothesis will be tested by the following specific aims: Aim 1: Define the colonic and ileal endoscopic and histologic findings in asymptomatic first-degree relatives of Crohn's disease patients. Aim 2: Correlate the endoscopic and histologic findings in asymptomatic first-degree relatives of Crohn's disease patients with a functional analysis of intestinal integrity. Aim 3: Look for evidence of intestinal immune activation in asymptomatic first-degree relatives of Crohn's disease patients." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENVIRONMENTAL FACTORS AND INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Higuchi, Leslie M.; Children's Hospital (Boston) Boston, MA 021155737 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This K08 award application is designed to enrich the candidate's career development in the epidemiology of gastrointestinal diseases. The program integrates mentored "hands on" experience in the proposed research plan on inflammatory bowel disease (IBD), didactic coursework to advance the knowledge and skills of the candidate, and enhanced interactions with other investigators through seminars, conferences, and scientific meetings. In the later years of the 5-year proposed program, the candidate plans to expand her work in the epidemiology of pediatric gastrointestinal illnesses. The candidate's sponsor is Dr. Richard J. Grand, an accomplished pediatric gastroenterologist with significant established experience in the field of IBD. Her co-sponsor is Dr. Graham A. Colditz, the Principal Investigator of the Nurses' Health Study at the Channing Laboratory. The program combines the institutional resources of the Children's Hospital, Boston and the Channing Laboratory of the Brigham and Women's Hospital, Harvard medical School. The Research proposal is a prospective cohort study to examine the association of environmental factors and the two types of IBD, Crohn's disease (CD) and ulcerative colitis (UC). The study base population will be composed of the Nurses' Health Study (NHS I) and the Nurses' Health Study II (NHS II) cohorts. Specific Aim 1 is to establish a database of confirmed cases of CD and UC in the NHS I and NHS II cohorts. Specific aims 2 through 4 will examine the association of specific dietary factors, smoking, and exogenous estrogen therapy and the development of CD or UC. Since the establishment of the NHS I in 1976 and the NHS II in 1989, information pertaining to participants' dietary intake and lifestyle factors has been updated at regular intervals, prior to the onset of CD or UC. Cases of CD and UC will be identified by biennial questionnaires and confirmed by medical chart review using established criteria. Analyses will compare age-specific incidence rates of CD and UC within different exposure categories, multivariate analyses, using the Cox proportional hazards model, will be performed. The proposed study will establish a unique database of repeated dietary and lifestyle assessments over several decades and will provide the opportunity to examine the influence of nutritional and lifestyle risk factors on IBD risk, improve our understanding of IBD pathogenesis, and define potential methods of prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPITHELIAL CHANGE/GENE EXPRESSION IN CROHN'S DISEASE Principal Investigator & Institution: Cohn, Steven M.; Paul Janssen Associate Professor; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904

Studies 23

Timing: Fiscal Year 2001 Summary: The intestinal epithelium represents the major interface between the mucosal immune system and the lumenal environment. The SAMP1/Yit mouse is a genetically inbred mouse line that develops ileitis that is similar to human Crohn's disease with near complete penetrance by 30 weeks of age. A major feature of disease in the SAMP/Yit mouse is the prominent architectural abnormalities of the ileal epithelium that occur early in the development of inflammation and ileitis. Ileitis does not develop in germ free SAMP/Yit suggesting a role for lumenal bacteria or environmentallyproduced epithelial damage in the development of chronic iteal inflammation. These observations raise the hypothesis that SAMP1/Yit mice have an altered epithelial response to injury which results in abnormalities which, in turn, leads to chronic iteal inflammation. Aim 1 will examine whether SAMP/Yit mice have an altered response to epithelial damage compared to control mice. The relationship of epithelial stem cell fate will be examined. Adoptive transfer techniques will be used to separate differences in injury-response that are intrinsic to the SAMP1/Yit epithelium from changes induced by the presence of activated T-cells and an inflammatory response. Changes in the expression of genes which regulate crypt epithelial apoptosis will also be examined. In aim 2 we will determine whether the changes in epithelial architecture or differentiation present in the SAMP/Yit mouse induce alterations in epithelial production of molecules that regulate the inflammatory response. The production of epithelial derived cytokines will be examined in n epithelial cells isolated from mice with ileitis and from heritable alterations in the properties of the epithelial alterations in the properties of the epithelial cells or are induced by inflammation and ongoing epithelial damage. In aim 3 we will examine heritable differences in epithelial expressed genes that may be involved in the development of ileitis in the SAMP/Yit mouse. This will be accomplished using cDNA microarray technology to identify differentially expressed genes that are encoded with chromosomal loci associated with susceptibility or development of disease as determined through the genetic analysis outlined in project 2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXTRACELLULAR MATRIX IN PEDIATRIC IBD Principal Investigator & Institution: Chakravarti, Shukti; Assistant Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Inflammatory bowel disease (IBD) is a progressive multi-step disease, with initiating and perpetuating events associated with immunoregulatory abnormalities, tissue damage and eventually clinical symptoms. Multiple factors, from genetic, environmental, microbial, immunologic, as well as non-immune elements of the mucosa are cited as involved in IBD pathogenesis. While the immunology of IBD has been the focus of intense studies, how the intestinal extracellular matrix (ECM) changes and contributes to progression of intestinal inflammation remains largely unknown. Our central hypothesis is that specific alterations in the intestinal basement membrane contribute crucially to early inflammation, while altered synthesis and modulation of interstitial ECM are important in progression of disease from early to chronic stages of disease. Furthermore, clinical evidence suggests that beyond certain common features, Crohn's disease (CD) and ulcerative colitis (UC), the two IBD subtypes, are diverse entities, with possibly fundamental differences in their ECM makeover. The current proposal will investigate this by elucidating ECM changes underlying early and chronic stages of IBD in pediatric and adult patients with CD and UC. Aim 1 will elucidate ECM gene expression profiles in early and late stages of UC and CD in pediatric and adult

24 Crohn’s Disease

patients by state-of-the-art DNA microarray techniques. Aim 2 will elucidate changes of selected basement membrane and interstitial ECM proteins in bowel tissues from pediatric and adult IBD patients. Aim 3 will elucidate changes in the same set of ECM components in induced and genetic murine models of colitis. Gene expression profiling of UC and CD tissue by DNA microarray will allow an unprecedented viewing of the entire repertoire of transcripts that differentiate UC from CD, as well as early from chronic stages of inflammation and fibrosis. In-depth studies of selected ECM components will provide a basic understanding of alterations that occur at the protein level. A newly developed animal model of intestinal fibrosis will offer the flexibility of following ECM changes from the onset to established to fibrosis stages of inflammation. Ultimately, the gene expression studies will provide the technology for a comprehensive comparison of animal models with human IBD and identify possible targets for new and better therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXTRACELLULAR INFLAMMATION

MATRIX

REGULATION:

INTESTINAL

Principal Investigator & Institution: Vogel, Jon D.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 05-FEB-2001 Summary: This proposal is aimed at the investigation of the extracellular matrix (ECM) in inflammatory bowel disease (IBD). Both forms of IBD, Crohn's disease (CD) and ulcerative colitis (UC) are characterized by a chronic inflammatory process that leads to functional and structural abnormalities, including prominent fibrosis and stricture formation. These are the result of altered ECM deposition and remodeling, but knowledge of the composition of the ECM in each form and stage of IBD is quite limited. In addition, little is known about the upstream regulatory events responsible for fibroblast activation and ECM production in IBD intestine. Thus, the central hypothesis is that changes in the ECM of CD and UC patients are specific for each type of IBD and are regulated by the interaction of mesenchymal cells with immune cells. This hypothesis will be tested by two specific aims. Aim 1 will define the composition of basement membrane ECM, interstitial ECM, and ECM remodeling enzymes in normal intestinal tissue, and the quantitative and qualitative changes present in tissues from CD and UC patients. Aim 2 will investigate whether the synthesis of ECM components and remodeling enzymes is differentially regulated in intestinal fibroblasts from control, CD and UC tissues, and how synthesis is regulated by cytokines and T-cell interaction. The results of these studies will expand knowledge of the mechanisms of intestinal inflammation and may lead to novel approaches to prevention or treatment of stricture formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FINE MAPPING THE IBD2 LOCUS Principal Investigator & Institution: Duerr, Richard H.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Twin studies and familial clustering of the idiopathic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), provide strong evidence that IBD is a heritable trait with complex genetics. The investigators' preliminary data show that they have replicated linkage between IBD

Studies 25

and the chromosome 12q13-14, IBD2 locus that was originally detected in a genome scan performed in the United Kingdom. They have also shown that most of the evidence for linkage to IBD2 comes from UC families, and that there is significant linkage heterogeneity between UC and CD at IBD2, which might, in part, explain the failure to observe linkage to IBD2 in some CD-dominated datasets. The investigators have found significant departure from random allele transmission to familial UC-affected individuals at a microsatellite that is located within the IBD2 linkage interval. Sequence analysis of two nearby candidate genes does not reveal coding region sequence variations that are likely to explain the linkage evidence. The investigators now propose to participate in the Inflammatory Bowel Disease Genetics Research Consortium as a Genetics Research Center, and they propose that fine mapping the IBD2 locus is a worthy project for the consortium to facilitate. The investigators propose to carry out a linkage disequilibrium mapping exercise across a three megabase region centered on the microsatellite that shows significant departure from random allele transmission to familial UC-affected individuals. The study sample will be limited to independent nuclear families with at least one UC-affected offspring, a family history of UC in another relative, and one or two unaffected parents. The investigators will develop a 20 kilobase grid of single nucleotide polymorphism (SNP) markers across the three megabase region, genotype the SNP markers in 576 members of independent nuclear families that meet the inclusion criteria, and use a variety of methods to analyze the patterns of linkage disequilibrium. Since the investigators will have at their disposal families, rather than examining single markers one at a time, they will use more powerful haplotype-based approaches to identify the interval that is most likely to contain the UC-predisposing genetic variant. The investigators will also recruit and phenotype study subjects for Inflammatory Bowel Disease Genetics Research Consortium projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FLUORESCENCE CORRELATION SPECTROSCOPY IN CLOSED NANOSTRUCTURED FLUID CHANNELS Principal Investigator & Institution: Korlach, Jonas; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853 Timing: Fiscal Year 2001 Summary: The etiologies of the two major inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, remain unknown, although it seems clear that both diseases can be influenced by environmental and genetic factors which contribute to initiation, amplification and prolongation of the inflammatory response. The most commonly prescribed drugs for IBD therapy are those which generate high concentrations of 5-aminosalicylic acid (5-ASA) in the colonic lumen. Despite known efficacy of these drugs for treatment of active disease and maintenance of quiescent disease, therapeutic mechanisms remain uncertain, due to uncertainty of the site of action of 5-ASA in the colonic mucosa. The Montrose group at Johns Hopkins University has developed ratiometric microscopy methods to image 5-ASA and its major metabolite (N-acetyl-5-ASA; Ac-5-ASA) simultaneously in living mouse colonic mucosa and we have extended this technique by the use of multiphoton microscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTION OF NUP475 IN THE GASTROINTESTINAL TRACK Principal Investigator & Institution: Worthington, Mark T.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904

26 Crohn’s Disease

Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): AU-rich elements (AREs) are critical regulators of cytokine and proto-oncogene messenger RNAs, preventing aberrant inflammation and uncontrolled growth. The protein Nup475 (also known at tristetraprolin and TIS11) is the prototype of a family of ARE-binding proteins with a common structural motif, the Cys3His domain, which we have proven has a novel structure distinct from the classical zinc finger. Nup475 destabilizes mRNAs by deadenylation of the polyA tail, as well as with effects on transcriptional activation and to promote apoptosis. This proposal will define determinants of Nup475 binding and potential mechanisms for its action, including the role of this protein in a mouse model of inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC STUDIES IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Cho, Judy H.; Assistant Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 15-MAR-1998; Project End 31-JAN-2003 Summary: The research project involves identifying susceptibility loci for IBD through genome-wide screening of affected relative pairs using non- parametric linkage analysis and gene identification through a variety of approaches. Unique aspects of the genetics of inflammatory bowel disease include the overlap between Crohn's disease and ulcerative colitis and its high prevalence in Ashkenazi Jews. Data on putative loci on chromosomes 16 and 12 are provided. Strategies for fine localization of loci, including fine-mapping by linkage disequilibrium, are proposed. alternative approaches to gene identification and mutation detection are discussed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF ACTINIC PRURIGO Principal Investigator & Institution: Elston, Robert C.; Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology. Hereditary susceptibility to sarcoidosis is suggested by reports of familial clustering and a higher prevalence in certain ethnic groups, particularly African-Americans. Candidate genes for the granulomatous inflammatory disorders, Blau syndrome and Crohn's disease have been localized to the centrometric region of chromosome 16. We therefore investigated whether this region is also involved in sarcoidosis. Using a sample of 35 African-American affected sibling pairs, we found no evidence of linkage in this general region, and could exclude from it a dominant gene with relative risk < 5, or a recessive gene with relative risk < 3,causing sarcoidosis. In particular, we concluded that the Blau syndrome gene does not have a major effect on sarcoidosis susceptibility. We plan to test for association of sarcoidosis with markers for other candidate genes and to perform a segregation analysis in order to test simultaneously for possible environmental risk factors and genetic mechanisms of disease transmission. This study is ongoing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 27

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Project Title: GI INFLAMMATION

NEMATODES

AND

FUNCTIONAL

RESPONSES

TO

Principal Investigator & Institution: Shea-Donohue, Terez; Professor; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, MD 20852 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): The overall hypothesis of the proposed studies is that the gastrointestinal tract contributes to host defense through stereotypic functional responses that are orchestrated by the profile of cytokines present. Crohn's disease and most murine models of colitis are linked to exaggerated production of Th1 cytokines. In contrast, the host defense to enteric nematode infection is dependent primarily on the type 2 cytokines, IL-4 and IL- 13. Of the type 2 cytokines, IL-4 is most important for the establishment of the Th2 profile and for the down regulation of Th1 pathway, yet there are few studies of IL-4, or other type 2 cytokines, in vivo. In addition, IL-13 shares many biological activities with IL-4 by acting at a common receptor chain. The central premise of this proposal is that colitis-induced changes in the smooth muscle and epithelial cell function will be improved by administration of exogenous IL-4 or IL-l3, or by upregulation of their endogenous production via nematode infection. We propose that the mechanism by which cytokines alter gut function involves receptor-mediated activation of Stat6 signaling pathways, mast cells and mast cell mediators, and enteric nerves. There are 3 specific aims. 1.) Determine that the profile of cytokines present in the gut controls epithelial cell and smooth muscle function in colitis and nematode infection; 2.) Determine the role of altered Th2 cytokines in colitis-induced alterations in epithelial cell and smooth muscle function; 3.) Determine the mechanisms of altered epithelial cell and smooth muscle function in mice with and without colitis and treated with IL-4, IL13, or nematode infection. Based on our preliminary data, we expect that type 2 cytokines have significant region-specific actions on the small and large bowel, and that restoration of the balance of type 1/type 2 profiles will be of therapeutic benefit to the impaired secretomotor function in IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLUCOCORTICOID-INDUCED OSTEOPENIA IN CHILDREN Principal Investigator & Institution: Leonard, Mary B.; Assistant Professor of Pediatrics; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Skeletal development is normally characterized by marked expansion of cortical dimensions and increases in trabecular density during childhood and adolescence. Glucocorticoids (GC) are widely used for many pediatric disorders; however, GC suppresses osteoblast function and bone formation. GC-induced osteopenia may be exacerbated by the effects of the underlying disease, such as delayed growth and maturation, malnutrition, vitamin D deficiency and increased bone resorption by inflammatory cytokines. The combined effects of decreased bone formation and increased bone resorption may be particularly detrimental to the growing skeleton. The hypotheses of this study are: (a) GC therapy during growth results in impaired bone mineral accretion with decreased trabecular and cortical density, decreased cortical dimensions, and decreased bone strength; and (b) the inflammatory, nutritional and growth-related effects of the underlying disease contribute to abnormal bone mineral accretion during growth. Childhood nephrotic syndrome (NS) usually responds to GC and remains in remission as long as high-dose GC therapy is continued. In contrast, Crohn's disease (CD) is treated with GC, but is independently associated

28 Crohn’s Disease

with poor growth and maturation, nutritional deficiencies and inflammation. Concurrent examination of the skeletal effects and disease characteristics of these two disorders will allow us to distinguish between GC- and disease-related effects. Unlike traditional densitometric measures of bone mass, peripheral quantitative computed tomography (pQCT) permits the discrete assessment of trabecular and cortical bone density and dimensions, and bone strength can be reliably estimated. The objective of this prospective cohort study is to use pQCT: (a) to identify determinants of trabecular and cortical bone development (density, dimensions and strength) among incident NS and CD patients prior to initiation of GC therapy; and (b) to determine the relationship between bone mineral accretion velocity (increases in density, dimensions and strength) and the pattern of GC exposure over a 12-month interval among 150 NS and 200 CD patients, adjusting for other growth- and disease-related determinants of bone mineralization. In healthy children, bone mass is highly correlated with growth and maturation; therefore, to understand the extent of bone deficits in children with NS and CD, these analyses will require a contemporary control group of similar age, gender, and ethnicity. The CHOP Normative Data Project (NDP) is an on-going initiative to collect cross-sectional measures of bone mineralization in healthy children. Our protocol will recruit 300 NDP participants to return for 6- and 12-month follow-up visits. The protocol will also examine levels of inflammatory cytokines and biomarkers of bone formation and resorption as predictors of bone mineral accretion during growth in NS and CD. Finally, the study will compare pQCT and DXA measures of bone mineral accretion in order to assess the utility of routine DXA in the assessment of GC effects in children. The accurate characterization of GC and disease effects on skeletal development is necessary to identify and evaluate targeted therapies to optimize skeletal architecture and peak bone mass in childhood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH FACTORS AND INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Lund, Pauline K.; Professor in Physiology, Pediatrics And; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-1995; Project End 31-MAY-2007 Summary: (provided by applicant): Major objectives of this research are to gain a better understanding of positive and negative mediators of inflammation induced intestinal fibrosis, an incurable complication of Crohn's disease (CD). Findings in animal models of acute colitis and in patients with CD indicate benefits of growth hormone (GH) therapy in CD but the documented fibrogenic effects of GH and insulin-like growth factor-I (IGF-I) which is induced by GH, support a hypothesis that GH therapy may exacerbate fibrosis in CD. Locally expressed IGF-I is up-regulated in myofibroblasts at sites fibrosis in CD and animal models of chronic intestinal inflammation implicating IGF-I as an endogenous mediator of fibrosis. Preliminary data support a hypothesis that suppressors of cytokine signaling (SOCS), may limit the fibrogenic actions of therapeutic or endogenous cytokines and growth factors in the inflamed intestine. Other data support a hypothesis that IGF-I interacts with another key cytokine, TNF-alpha to mediate collagen synthesis or proliferation in intestinal myofibroblasts, key cellular mediators of fibrosis in CD. Specific aims are as follows:Aim 1 will define if systemic GH increases fibrosis, circulating or locally expressed IGF-I during PG-PS induced enterocolitis. Cellular sites and levels of SOCS expression will be assessed to verify that SOCS2 or SOCS3 are expressed at in vivo sites that would permit them to limit fibrosis.Aim 2 will define if IGF-I mediates GH action on collagen synthesis or

Studies 29

proliferation in intestinal myofibroblasts and test whether SOCS limit GH or IGF-I action.Aim 3 will define if mice with absolute or mesenchyme-specific SOCS2 deficiency show altered fibrosis, JGF-I induction or GH action during TNBS-colitis.Aim 4 will define mechanisms if TNF-alpha has additive or synergistic effects with IGF-I, to induce collagen synthesis in intestinal myofibroblasts and if SOCS limit these effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: H HEPATICUS--PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Schauer, David B.; Associate Professor; Div of Comparative Medicine; Massachusetts Institute of Technology Cambridge, MA 02139 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from the applicant's abstract): The human inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are multifactorial disorders whose etiology remains unknown. Animal models have been developed to help understand the complex interaction between the immune system and intestinal antigens - particularly bacteria - which appear to be involved in the pathogenesis of disease. Infection with the mouse pathogen Helicobacter hepaticus has been associated with disease in mice which are genetically and/or immunologically predisposed to the development of IBD. H. hepaticus, like the human gastroduodenal pathogen H. pylori, expresses putative virulence factors which may contribute to chronic mucosal inflammation, epithelial cell proliferation, and an increased risk for cancer. The investigators propose to test the hypothesis that infection with H. hepaticus is sufficient for expression of disease in mice which are predisposed to the development of IBD. They also propose to identify the bacterial virulence factors of H. hepaticus which are involved in the pathogenesis of IBD in the mouse models. These studies will characterize the mechanism by which infection with a single bacterial species can affect expression of disease in mouse models of IBD. It is hoped that these studies will lead to the development of rational therapy for patients suffering from Crohn's disease and ulcerative colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HELICOBACTER HEPATICUS INDUCED TYPHLITIS Principal Investigator & Institution: Myles, Matthew H.; Veterinary Pathobiology; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Dr. Matthew H. Myles, the candidate for the SERCA grant, is a burgeoning investigator who has demonstrated commitment to biomedical research through his many accomplishments. Most pertinently, Dr. Myles earned his DVM, residency certification in comparative medicine, and he is a candidate for a PhD in veterinary pathobiology with an expected graduation date of summer semester 2003. During the period of SERCA grant, Dr. Myles will obtain additional training that will help prepare him as an independent research investigator. To develop his scientific skills Dr. Myles will participate in a variety of seminars and journal clubs relevant to his area of research. Dr. Myles will attend specialized topical courses at the Cold Spring Harbor Laboratory and The American Association of Immunologists advanced course in immunology. Perhaps most advantageous, Dr. Myles will receive outstanding research mentoring from Drs. Craig Franklin, Frank Booth, and Brian Dieckgraefe. The focus of Dr. Myles' research project is characterization of the host response to Helicobacter

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hepaticus induced-enteritis. Preliminary studies show that development of enteritis in mice is dependent upon host-susceptibility factors and characterized by a Thl mucosal immune response. The short-term goals of this grant application are to profile global gene expression changes in response to H. hepaticus induced typhlitis, to delineate key regulators of the mucosal immune response, and determine the role of epithelium in the pathogenesis of disease. The long-term goal is to develop Helicobacter hepaticusinduced typhlitis into a rodent model of Crohn's disease. Working under the tutelage of Drs. Craig Franklin, Frank Booth, and Brian Dieckgraefe provides a unique opportunity for learning. Their combined expertise in the fields of rodent Helicobacter infections, host-pathogen interactions, animal model development, DNA array technology and analysis, cellular signaling pathways, and treatment of inflammatory bowel disease is essential to the success of this project. CANDIDATE Dr. Myles received his B.S. degree in biology in 1986 and his D.V.M. degree in 1994 from Colorado State University. He completed his residency in comparative medicine at the University of MissouriColumbia in 2001 and he is board certified in Laboratory Animal Medicine. He is expected to receive his Ph.D. degree in August 2003. As an undergraduate student, he worked as a part-time student researcher in Dr. Edward A. Hoover's laboratory at Colorado State University. During his pursuit of the veterinary medical degree, he did a summer internship with Dr. Andrew Lackner at the New Mexico Regional Primate Research Laboratory. After earning the D.V.M. degree, he worked in a small animal veterinary practice in Colorado. During his first year in the Comparative Medicine Program at the University of Missouri, he completed intensive six-month rotations in clinical laboratory animal medicine and diagnostic pathology of rodents. During his second year, he worked in the laboratory of Dr. Cynthia Besch-Willford, assisting in the characterization of new mice strains. He joined the laboratory of Dr. Craig Franklin during his third year of residency training to pursue his Ph.D. thesis research. CANDIDATE EVALUATION: Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HELMINTHIC CONDITIONING OF THE MUCOSAL IMMUNE RESPONSE Principal Investigator & Institution: Weinstock, Joel V.; Professor; Internal Medicine; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: (Adapted from the Applicant's Abstract): The frequency of Crohn's disease (CD) has increased substantially in industrialized countries over the last 40 years. CD is an overly exuberant Th1 response probably directed at normal constituents of the intestinal flora. Helminthes live within the human gut interacting with the mucosal immune system. The host mounts a mucosal Th2-type reaction to limit helminthic colonization. Helminthic worms and their eggs are potent stimulators of mucosal Th2 and suppressors of Th1 responses. Th2-type reaction to a helminth can modulate the immune response to other concomitant parasitic, bacterial and viral infections. Many people live in increasingly hygienic environments and acquire fewer helminthes. The major hypothesis of this proposal is that helminthic colonization conditions our mucosal immune system to appropriately respond to stimuli without excessive release of strong tissue-destructive, Th1 cytokines. Failure to undergo helminthic colonization and to experience this mucosal conditioning predisposes people to Crohn's disease, which is an overly exuberant Th1 reaction. To test this hypothesis, the investigator is using normal mice exposed to TNBS and IL-10 mutant mice that develop IBD spontaneously to show if exposure to a murine intestinal helminth affords protection against the

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subsequent aberrant intestinal Th1-type inflammation. The project has three specific aims. Aim 1 will determine if helminthes protect mice from acute TNBS colitis and determine the role of T cells and cytokine pathways in mediating this protective process. Aim 2 will evaluate the effect of helminthic conditioning on the natural development of chronic mucosal inflammation in the IL-10-/- mouse. The investigator will determine if exposure to helminthes can prevent or down-modulate ongoing spontaneous Th1-type colitis. Also, the investigator will identify mechanisms through which this exposure affords protection. Aim 3 will determine if immune dysregulation or various agents used to treat IBD alter the host/helminth interaction. These experiments are important, since it must determined how patients with dysregulated immunity may respond to docile live helminthes used as therapy. This investigation could provide new insight into the pathogenesis of CD. The results may lead to novel therapies for disease prevention and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HPEPT1 IN INTESTINAL INFLAMMATION Principal Investigator & Institution: Merlin, Didier; Pathology; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Many diseases of the human intestine are, in the active phase, histologically characterized by infiltration of the crypt epithelium by neutrophils (PMN). PMN subsequently accumulate in the crypt lumen to form "crypt abscesses". The colonic lumen normally contains bacterial derived products such as Nformylated peptides in concentrations capable of activating PMN transmigration. Under my K01 award I have demonstrated that i) fMLP (a model N-formyl peptide) is transported by the di-tripeptide/H+ cotransporter hPepT1; ii) hPepT1-mediated epithelial transport of fMLP enhances neutrophil-epithelial interactions; iii) hPepT1 can be aberrantly expressed in the colon under inflammatory states such as chronic ulcerative colitis and Crohn's disease; iv) hPepT1 mediated uptake of small n-formyl peptides, such as fMLP, into the cell cytoplasm increases immune accessory molecules such as MHC Class 1. In my first R01 application I propose to extend these finding at the molecular level. Thus the general aim of this proposal will be to better understand the intracellular signaling events (Specific Aim 1) and the effect on the regulation of inflammatory responses (Specific Aim 2 and 3) of PepT1 mediated IMLP transport. In Specific Aim 4, in vivo experiments will be aimed to study the inflammatory effects of hPepT1-mediated fMLP transport in the rat intestine and the in vivo functional effects of hPepT1 expression on the mice colonic epithelial cells. The project involves a variety of biochemical methods with emphasis on molecular approaches. The completion of this proposal should molecularly define a link between an active transport process and intestinal inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HYPERBARIC OXYGEN THERAPY FOR PERINEAL CROHN'S DISEASE Principal Investigator & Institution: Noyer, Charles; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001 Summary: Perineal disease is a frequent complication of Crohn's disease. Approaches to therapy have included, surgery and various medications, which may require time to

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work or can cause significant toxicity. Several papers have described the beneficial results of hyperbaric oxygen therapy (HBO) in patients with severe or refractory perineal disease. The role of hyperbaric therapy in larger groups or less severely affected patients has not been studied. Additionally, the minimum number of treatments required for initial or complete healing of perineal disease in this population has not been described. Patients with documented perineal Crohn's disease who meet the eligibility criteria will be randomized to treatment with HBO or observation, then crossed over to the other group after 6 months. Crohn's disease activity will be measured biweekly using the Harvey-Bradshaw index, and perineal disease monitored biweekly using the Cardiff Classification. Patients will be enrolled on an intention-totreat basis. A maximum of twenty sessions of HBO therapy will be given to each patient. The endpoint is complete resolution of perineal disease. We will monitor side effects of HBO therapy including inner ear barotrauma, pulmonary complications, development of visual difficulties and claustrophobia, among others. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFICATION OF IBD SUSCEPTIBILITY GENES Principal Investigator & Institution: Silverberg, Mark S.; Mount Sinai Hospital (Toronto) 600 University Ave Toronto, Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis, are chronic conditions with a multifactorial etiology involving interplay between a number of genetic and environmental factors. Several lines of epidemiological evidence support the hypothesis that genetic factors are particularly important in the pathogenesis of IBD and the results of seven genome-wide scans published to date have identified a number of IBD susceptibility loci. Although the disease variants within most of these loci have not been identified as of yet, the first CD-associated gene, Nod2, has been identified within the IBD1 susceptibility locus. The inheritance patterns of IBD are complex and are associated with considerable genetic heterogeneity. Thus, identification and characterization of all the genes which cause and/or modulate IBD is required to fully appreciate IBD pathogenesis and will impact substantively on the development of improved molecular diagnostic and therapeutic strategies. Additionally, better understanding of the complex genetic mechanisms leading to the onset of IBD may also provide a framework for elucidating the environmental factors which contribute to disease onset. The Mount Sinai Hospital IBD Center in Toronto has previously performed a genome-wide search for IBD susceptibility loci. The results of this analysis have revealed loci on chromosomes 19p13 and 6p to be linked to IBD. The data generated in this genome-wide search support the hypothesis that important IBD susceptibility genes lie in these chromosomal regions. These data, therefore, provide the rationale for this application as a Genetic Research Center in the context of the proposed IBDGRC. Therefore, the specific aims of this proposal are to: 1) refine the IBD susceptibility regions on chromosome 19p13 and 6p; 2) identify the susceptibility genes on chromosomes 19p13 and 6p; and 3) participate in large scale efforts to identify important susceptibility genes for IBD by contributing clinical data and biological samples in the context of the IBDGRC. The broad objective of this proposal is to make significant progress in dissecting the genetic mechanisms contributing to IBD pathogenesis. Accomplishing this will lead to the ability to identify "at risk" individuals and to intervene with targeted preventative strategies. The potential also exists for the subsequent development of improved diagnostic tests and safer and more efficacious therapies.

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

Project Title: IGF-I AND IGFBP-5 IN INTESTINAL FIBROSIS Principal Investigator & Institution: Zimmermann, Ellen M.; Associate Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: (Adapted from the Applicant's Abstract): Intestinal fibrosis is a common sequela of chronic intestinal inflammation in patients with Crohn's disease. Data suggest that smooth muscle cells, fibroblasts and myofibroblasts are the major sites of intestinal collagen synthesis leading to stricture formation. Insulin-like growth factor I (IGF-I) is a potent fibrogenic peptide that is increased in fibrotic intestine of patients with Crohn's disease. IGF binding protein 5 (IGFBP-5) is a unique protein that associates with the extracellular matrix (ECM) and increases the actions of IGF-I on its target cell. IGF-I has a mitogenic effect on intestinal smooth muscle and increases collagen synthesis and synthesis of IGFBP-5 by rat intestinal smooth muscle cells (RISM) in vitro. IGF-I acts through the type I IGF receptor to activate multiple signal transduction pathways including the phosphatidylinositol 3-kinase (Pl3K) and the mitogen-activated protein kinase (MAPK) pathways. IGF-I regulates IGFBP-5 synthesis by transcriptional and posttranscriptional mechanisms and increases IGFBP-5 mRNA stability by factors that may act through newly recognized regions of the 3' UTR that modulate mRNA stability. PI's hypothesis is that IGF-I is increased in inflamed intestine and acts on intestinal smooth muscle cells to increase synthesis of collagen and IGFBP-5. IGFBP-5, in turn, associates with the ECM near the target cell and enhances the fibrogenic actions of IGF-I on smooth muscle. Factors that mediate IGF-I signal transduction and that modulate IGFBP-5 expression are key to the actions of IGF-I in the gut. This grant application will study basic mechanisms of IGF-I mediated effects on smooth muscle cells. Our specific aims are 1) to define the relative contributions of the Pl3K and the MAPK pathways to IGF-I signaling in smooth muscle cells, 2) to define the mechanism(s) that regulate IGFBP-5 mRNA stability, 3) to modulate IGFBP-5 in vivo and determine the effect on intestinal inflammation and fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNOGENETIC MECHANISMS OF EXPERIMENTAL CROHN'S DISEASE Principal Investigator & Institution: Cominelli, Fabio; Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-AUG-2005 Summary: Crohn's disease (CD) is a debilitating condition of unknown etiology that is poorly responsive to currently available treatments. Although there is increasing evidence that genetic, immunological, and environmental mechanisms may be involved, the precise cause(s) of this disease remains unclear. Indirect evidence from human studies suggests that CD may be an "autoimmune" disease initiated by a dysregulated immune response against an "unknown" antigen in a genetically susceptible host. One of the difficulties encountered in studying CD has been the lack of appropriate animal models. The unique feature of this proposal is the use a new strain of mice, referred to as SAMP1/Yit. Unlike any other animal model of IBD, these mice spontaneously develop ileitis without genetic or immunologic manipulation. In our colony, virtually 100% of SAMP1/Yit mice develop a severe, chronic transmural ileitis by twenty weeks of age

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that closely resembles human CD both macroscopically and histologically. The overall objective of the present research proposal is to investigate the key pathogenic mechanism(s) underlying this spontaneous murine model of human CD. The Program Project will be directed by Dr. Fabio Cominelli and will consist of four Projects and three Cores. Project 1, headed by Dr. Fabio Cominelli, will focus on the role of pathogenic and regulatory T cells as well as pivotal Th1 cytokines in mediating chronic intestinal inflammation in this model. Project 2, headed by Dr. Marcia McDuffie, will identify susceptibility genes involved in the predisposition to ileitis in SAMP1/Yit mice. Project 3, headed by Dr. Steven Cohn, will investigate the role of epithelial cells in initiating ileitis in this model. Project 4, headed by Dr. Klaus Key will study the mechanisms of intestinal cell adhesion and inflammatory cell trafficking in SAMP1/Yit mice. These projects will be supported by an Administrative Core which will provide administrative support and coordination. An Animal/Morphology Core will centralize the production and breading of SAMP1/Yit mice with ileitis, provide for centralized pathologic and histologic analysis and generate stocks of genetically modified mice for use in the projects. Lastly, a Cytokine/Immunology Core will provide cytokine analysis as well as T cell transfer and bone marrow chimera experiments for the four projects. The longterm goal of this Program Project is to understand key pathogenic mechanisms of experimental CD in order to begin to develop a cure for this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOMODULATION IN INFECTIOUS DIARRHEA Principal Investigator & Institution: Klapproth, Jan-Michael A.; Medicine; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The goal of the principal investigator is to continue to develop intellectual, technical, and analytical skills to become an independently funded physician-scientist investigator in microbial pathogenesis, examining the effect of bacterial products on the immune system. The program to achieve this goal will consist of additional didactic and laboratory training in basic immunology, lymphocyte signal transduction, and microbial and molecular genetics. Bacterial immunomodulatory products are of utmost importance in infectious diseases and their prevention. For example, C. difficile toxin A and B are implicated in the development of pseudomembranous enterocolitis, and cholera toxin functions as an adjuvant in oral immunization. In this proposal we will continue to characterize a novel toxin from Enteropathogenic E. coli (EPEC), resulting in marked inhibition of T cell activation. The inhibitory gene, lifA (lymphocyte inhibitory activity), encodes for a protein with the putative size of 366kDa. The lifA gene product, lymphostatin, bears significant similarity to the N-terminus of large Clostridial cytotoxins, encoding for a glucosyltransferase motif, which is critical for their specific activity. Similar immunosuppressive genes and biological activity have been identified in related bacteria, including other EPEC strains, Enterohemorrhagic E. coli, and the mouse pathogen C. rodentium. Our hypothesis is that the glucosyltransferase motif in lymphostatin is critical for the observed immunosuppression, leading to inhibition of defined lymphocyte subpopulations of the adaptive immune response and allowing firm establishment of enteric Gram negative infection. To test the hypothesis, we propose: Aim 1: To identify the co-substrate and target molecule(s) in lymphocytes exposed to lymphostatin. Aim 2: To investigate intracellular activation pathways in defined lymphocyte populations affected by lymphostatin, resulting in suppression of IL-2, IL-4, and IFN-gamma expression. Aim 3: To investigate whether lymphostatin

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suppresses the mucosal adaptive immune response and firmly establishes C. rodentium enteric infection in vivo. The proposed research project will contribute to the understanding of immune mechanisms involved in the pathogenesis of chronic infectious diarrhea and gastrointestinal inflammation as seen in Crohn's disease and ulcerative colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOMODULATION IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Sands, Bruce E.; Director, Clinical Ibd Research; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: The overall goals of this proposal are: 1) to determine whether initiation of immunomodulatory therapy early in the course of Crohn's disease alters its natural history; and 2) to prepare the principal investigator for an independent career in clinical investigation in gastroenterology. Crohn's disease is a chronic, idiopathic inflammatory condition of the gastrointestinal tract. The currently accepted strategy of medical therapy for Crohn's disease is a graded, stepwise approach. This strategy is intended to improve symptoms while minimizing exposure to side effects. Immunomodulatory therapies are generally not employed until repeat trials of other medications have failed. This approach is based on assumptions that more effective drugs are inherently more dangerous and that the primary goal of therapy should be alleviation of symptoms. Recent reports provide evidence to contradict both assumptions: 1) there is an extensive safety record with highly effective immunomodulatory agents; and 2) alleviation of symptoms often does not reflect biologic remission of the disease or delay its sequelae. Therefore, we propose that early initiation of immunomodulatory therapy will significantly improve the treated natural history of Crohn's disease over the generally accepted, stepwise approach. To test this hypothesis, the investigator proposes a longterm, randomized, double-blind, placebo-controlled trial of additive therapy with the immunomodulatory agent 6-mercaptopurine versus placebo (standard care) initiated within 12 months of diagnosis. The primary analysis to test this hypothesis will be a comparison of the time to first surgery with up to 3 years of follow-up from initiation of study drug among the two treatment groups. The acronym chosen for this study is NOCIS for "New Onset Crohn's Intervention Study." Retrospective and prospective planning studies, including a short-term randomized, controlled trial, will be performed to finalize details of study design and execution of the proposed long-term trial. Continued involvement in the didactic activities of the MGH Center for the Study of Inflammatory Bowel Disease will further the principal investigator's knowledge in inflammatory bowel disease, while the support of the Clinical Research Program will support the clinical research aspects of this proposal. The principal investigator will also seek advanced training in the design, execution, and analysis of clinical trials in the course of completing a Master of Science in Clinical Epidemiology at the Harvard School of Public Health. The principal investigator seeks to become an independent clinical investigator by completing the didactic and scientific portions of this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATORY BOWEL DISEASE IN TCR-MUTANT MICE Principal Investigator & Institution: Bhan, Atul K.; Associate Pathologist; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2002; Project Start 15-SEP-1994; Project End 31-AUG-2007

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Summary: (provided by applicant): The spontaneous chronic colitis in T cell receptor (TCR) alpha mutant (knockout) mice provides an excellent experimental model of inflammatory bowel disease. The colitis shares many features with ulcerative colitis and is mediated by the T helper 2 pathway. Colonies of TCRalpha knockout mice deficient in cytokines and B cells have been developed at the Massachusetts General Hospital. The project will focus on the hypothesis that an unregulated immune response to enteric bacterial antigens at the mucosal site results in chronic colonic inflammation and autoantibody production. Certain enteric bacteria may play a protective role in the development of intestinal inflammation. The role of the appendix in the presentation of enteric bacterial antigens and in providing both pathogenic and regulatory cells in the pathogenesis of chronic colitis will be explored. A major focus of the project will be to examine the regulatory role of B cells in colitis. We have developed a new model of granulomatous colitis in B cell and lL-4 deficient TCRalpha knockout mice. Thus, the development of two distinct colitis models in mice that are of genetically of identical background and exposed to the same environment, provides an opportunity to analyze the mechanisms involved in T helper 2-mediated ulcerative colitis-like and T helper 1mediated Crohn's disease-like colitis. Additional models of T helper 1-mediated colitis in IL-10 KO mice and CD45RB high transfer model will also be studied. Experiments will be designed to develop specific interventions, including B cell based therapies, to prevent and suppress chronic intestinal inflammation and contribute to the development of new therapeutic modalities for human inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTESTINAL INFLAMMATION ORCHESTRATED BY PATHOGENS Principal Investigator & Institution: Mc Cormick, Beth A.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: The active phase of both Salmonella-associated gastroenteritis and chronic states of inflammatory bowel disease IBD), such as ulcerative colitis and Crohn's disease, is characterized histologically by polymorphonuclear leukocyte (PMN) migration into and across the epithelial lining of the intestine. These events result in acute inflammation of the epithelium and subsequent epithelial dysfunction. The degree of PMN transmigration into intestinal crypts and the formation of crypt abscesses is indicative of disease severity and is used clinically to evaluate the activity of IBD. It is unclear what triggers directional movement of PMN across the intestinal epithelium. Towards this end, we have recently shown that epithelial cells themselves can send such signals to underlying PMN and these signals are regulated by enteric flora, such as S. typhimurium. The broad long term objectives of this proposal are to investigate the molecular mechanism by which epithelial cells in response to microbial pathogens can signal to PMN and orchestrate their directed migration. Once we begin to understand the basis of such transcellular signaling important in promoting disease flares of S. typhimurium pathogenesis, it may be possible to develop novel therapeutic strategies aimed at treatments for and ameliorating IBD. The specific aims are ultimately directed at achieving this goal, and are three-fold. Specific Aim 1 is designed to determine the nature of S. typhimurium virulence factors and define their contribution to the epithelial orchestration of mucosal inflammation. Specifically, we will delineate how S. typhimurium SipA, SopB, and SopA secreted proteins interfere with the signaling pathways which lead to epithelial orchestration of mucosal inflammation by expression of these proteins in epithelial cells using adenoviral expression vectors. Functional effect of expression of these proteins on orchestration of proinflammatory events which

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govern PMN transepithelial migration will be correlated with morphological consequences by both confocal and electron microscopy. Specific Aim 2 is designed to identify the signal transduction cascades which lead to the release of the proinflammatory chemoattractant PEEC and will employ several different approaches which include determining the relationship between S. typhimurium invasion and the apical epithelial release of PEEC, examination of the role of the JNK-pathway, determining the effects of small GTPase (cdc42, rac-1, and Arf6) expression on the ability of S. Typhimurium to induce PMN transepithelial migration by expression of dominant inhibitory mutants using adenoviral expression vectors, examining the role of phosphinositide signaling, and determining whether the ability of S. typhimurium to elicit PEEC secretion correlates with their ability to induce an increase in intracellular calcium in model intestinal epithelia. Specific Aim 3 is designed to characterize a recently identified pro-inflammatory PMN chemoattractant. The first part of this aim will elucidate the structure of PEEC utilizing HPLC purification, NMR analysis, mass spectrometry and sequence analysis, while the second part of this aim will define PEEC's relationship to other PMN chemoattractants including its ranking in the PMN chemoattractant hierarchy, will determine whether PEEC is able to activate other immune-type cells as well as assess the role of PEEC in inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTL PEDIATRIC INFLAMMATORY BOWEL DISEASE (IBD) MEETING Principal Investigator & Institution: Fiocchi, Claudio; Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Funding is requested for a scientific workshop entitled "International Pediatric Inflammatory Bowel Disease (IBD) Meeting". The workshop is under the auspices of Case Western Reserve University and the Crohn's & Colitis Foundation of America, and will be held from September 16 through 18, 2003. The workshop will be attended by approximately 100 participants and will include five scientific sessions, each one presided by leading investigators and including 6 speakers. The conference, the very first ever of its kind, will focus on the issue of the raising incidence of IBD in the pediatric population worldwide, and address the serious lack of studies on the pathogenesis of Crohn's disease and ulcerative colitis in children. The major topics will include the development of the immune system in children and its impact on neonatal and adult immunity, the differential reactivity of T-cells in early and adult life in health and disease, the intestinal microbiota and its relevance to IBD, the impact of environmental factors on IBD pathogenesis and manifestations, and new trends in the treatment to pediatric IBD in face of emerging diagnostic and therapeutic technologies. These are completely novel and unexplored areas of undeniable importance to IBD. The outcome of the workshop is expected to define the reasons for the lack of pathophysiology-based research in pediatric IBD and stimulate investigation in areas so far unexplored by pediatric gastroenterologists and IBD investigators. A major goal of the conference is to foster a close interaction and scientific exchange between scientists outside of the field of IBD with established and new investigators interested in Crohn's disease and ulcerative colitis. An additional goal of the workshop is to expose a substantial number of trainees, post-doctoral fellows and junior faculty members to novel ideas, concepts and methodologies that will become the center of scientific attention in pediatric IBD in the immediate future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISIS2302 IN STEROID DEPENDENT CROHNS DISEASE Principal Investigator & Institution: Korzenik, Joshua; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: KALLIKREIN KININ SYSTEM IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Colman, Robert W.; Director; Thrombosis Research Center; Temple University 406 Usb, 083-45 Philadelphia, PA 19122 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2003 Summary: We have shown that bacterial products (proteoglycan-polysaccharide, PGAPS) found in the lower bowel produce chronic granulomatous inflammation similar to Crohn's disease (regional ileitis) in genetically susceptible rats as well as associated systemic inflammation. Activation of the contact system (CS) in plasma produces plasma kallikrein which activates neutrophils, cleaves high molecular weight kininogen (HK) and releases bradykinin which induces pain, swelling, diarrhea, and muscle contraction, all of which are characteristic symptoms of intestinal inflammation. We have shown that the CS activates mediates acute and chronic phases of intestinal inflammation in susceptible Lewis rats and is selective activated in these rats, but not in the resistant Buffalo rats. A specific kallikrein inhibitor decreases CS activation, acute inflammatory changes (edema, neutrophil infiltration), chronic intestinal inflammation and the systemic complications (arthritis, splenomegaly, hepatomegaly, leukocytosis, and the acute phase reaction. We have recently shown that there is a molecular difference between the plasma kininogen from Lewis rats which results in more rapid cleavage to yield bradykinin than in Buffalo rats. This proposal will test two hypotheses: (1) genetic differences between kininogen in susceptible and resistant rats result in selective activation of the Plasma Cs mediating certain of the pathological changes; (2) locally, intestinal tissue kallikrein is released and contributes to inflammatory changes. We will define the relationship of the single amino acid change to the functional consequences. In the view of the efficacy of plasma kallikrein inhibitors in blocking enterocolitis, we will use recombinant HK derivatives and peptides derived from HK which can distinguish in vitro whether plasma kallikrein stimulation of neutrophils or bradykinin actions are responsible. In vivo, we will use kinin receptor blockers to define the mechanisms responsible for the enterocolitis. If bradykinin (BK) is responsible, then BK receptor blockers already used in clinical trials may merit evaluation in the therapy of chronic granulomatous enterocolitis. If plasma kallikrein is responsible, the development of plasma kallikrein inhibitors should be pursued. We will study the effect of total kininogen deficiency on the development of acute and chronic enterocolitis and systemic inflammation. Our recent studies show that tissue kallikrein (TK) is localized in macrophages of chronic granulomas and that TK may be secreted from inflamed intestinal cells. We will assay low molecular weight kininogen, the substrate of Tk using a newly designed assay as well as the natural protease inhibitor of TK. We will study the behavior of the TK system in intestinal cell lines and macrophages stimulated with PGAPS or inflammatory cytokines. In vivo, we will use a new specific TK inhibitor to attempt to modulate intestinal and systemic inflammation. These studies should demonstrate important mechanisms in the pathogenesis of inflammatory bowel disease. Assays of the CS and/or TK systems could distinguish active form inactive

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disease. In addition, the inhibitors used alone or in combination could serve in the future as potential therapeutic agents of human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LINKAGE ANALYSIS OF FAMILIAL PSORIASIS Principal Investigator & Institution: Elder, James T.; Professor; Dermatology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 10-MAR-1994; Project End 28-FEB-2003 Summary: (Adapted from the applicant's abstract)-Psoriasis is a common, HLAassociated disease of presumed immunopathogenesis. The hypothesis to be tested is that susceptibility to psoriasis is oligogenic, with at least one gene residing in the HLA region. Published results from a cohort of 224 affected sibling pairs have demonstrated three regions of suggestive linkage: HLA (Class I end, Zmax = 3.52), chromosome 16q (Zmax = 2.50), and chromosome 20p (Zmax = 2.62). Linkage to Class I and to 20p has been reported by others. The region in 16q overlaps with a recently identified locus for Crohn's disease. Since psoriasis occurs more commonly in patients with Crohn's disease than in controls (RR = 7. 1, p 1); (2) genotype candidate regions from Aim 1 at 5 cM intervals in all available pairs testing for linkage, increasing marker density to 0.5-1 cM in regions of suggestive or significant linkage (lod >2), and narrowing target intervals to approximately cM by multipoint allele sharing and linkage disequilibrium techniques; and (3) identify genes residing in the intervals identified by Aim 2 and in the TNF-HLA-C interval using the human transcript map. Allelic variation of the genes will be tested for segregation using TDT and MBSA, and by identifying alleles shared across haplotypes in regions of strong linkage disequilibrium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MAPPING THE GENES FOR INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Yang, Huiying; Assistant Professor and Associate; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001; Project Start 15-MAR-1999; Project End 28-FEB-2003 Summary: Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and ulcerative colitis (UC)-- two chronic idiopathic inflammatory diseases of the gastrointestinal tract. Studies of the genetic epidemiology and of animal models demonstrate that these diseases are determined in large measure by genetic factors. These data also indicate that UC and CD share some common genetic factors, but have additional distinct genetic determinants. However, the specific nature of the genetic factors predisposing to both or either of these diseases remains poorly defined. In order to identify susceptibility genes for these diseases, we have already initiated a systematic scan in CD families with markers at 10 cM interval and identified 19 regions where genes predisposing to IBD may be located (including loci on chr. 12 and chr. 16 and the MHC region). The goal of this project is to further confirm and refine the initial linkage findings and ultimately to identify the genes predisposing an individual to IBD or subforms of IBD. We will first perform, with an increased number of CD families, fine linkage mapping to a density of 2-3 cM in those regions where initial evidence for linkage to CD was observed (aim 1). Any regions showing evidence of linkage to CD will then be tested in UC and mixed (both UC and CD) families (aim 2). For those regions where there is strong evidence of linkage, linkage disequilibrium mapping will be carried out, utilizing both family and case-control panels in a multi-phase design to narrow the region containing the susceptibility genes (aim 4). Then, candidate genes at

40 Crohn’s Disease

these regions will be evaluated by screening for mutations and changes in the level of expression (aim 5). All linkage and linkage disequilibrium mapping analysis will be conducted in the sample as a whole, as well as in subgroups defined by ethnicity, subclinical markers, or known linked loci (aim 3). Both two point and multipoint linkage analysis methods will be employed for all linkage analyses. The transmission/disequilibrium test will be used for linkage disequilibrium mapping. This study will eventually lead to identifying genes predisposing to these most debilitating of gastrointestinal diseases, with implications for the assessment of individual risk for IBD, for diagnosis and clinical management of patients, and for basic understanding of the mechanisms of disease pathogenesis fundamental for the development of novel and individualized therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MDR-1 EXPRESSION IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Farrell, Richard J.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 15-JUL-2000; Project End 30-JUN-2005 Summary: (adapted from the application) A research program will be undertaken by the applicant, Richard J Farrell MD, in the Division of Gastroenterology at the Beth Israel Deaconess Medical Center (BIDMC). Dr. Farrell has had substantial basic and clinical research exposure during his Gastroenterology fellowships in Dublin and Boston, during which he showed impressive productivity and commitment to an academic career in patient orientated research. Dr Ciaran P. Kelly, Associate Physician in the Division of Gastroenterology, BIDMC, and Dr J Thomas LaMont, Chief of Gastroenterology at BIDMC will serve as mentors. Despite the impressive strides that have been made in the diagnosis and management of inflammatory bowel disease (IBD), as many as 20% of patients with ulcerative colitis (UC) and over one-third of patients with Crohn's disease (CD) have disease which is refractory to routine medical therapy, particularly glucocorticoids. This frequently results in multiple hospital admissions as well as the need for surgery. The Multidrug Resistance gene (MDR-1) encodes a cell membrane based drug efflux pump (Pp-170) which actively transports MDR substrates, including glucocorticoids and other immunosuppressants used to manage IBD, out of target cells thereby lowering their intracellular concentration to subtherapeutic levels. The long term goal of this project is to determine whether inhibition of MDR function influences the response of IBD patients to glucocorticoids and other immunosuppressive therapy. The underlying hypothesis for this application is that glucocorticoid-refractory IBD is directly related to overexpression of MDR. The specific aims of this project are; 1) To determine whether the level of human peripheral blood lymphocyte (PBL) MDR expression is independent of disease activity and is an important determinant of the response of IBD patients to glucocorticoids; 2) To determine whether the level of MDR expression significantly influences intracellular PBL glucocorticoid levels and function in IBD patients; and 3) To determine whether the level of constitutive PBL MDR expression is genetically determined. In addition to the research component the applicant will undertake a Masters in Public Health at Harvard School of Public Health. This will include formal research training in 1) Research ethics, 2) Clinical epidemiology, 3) Biostatistics 4) Clinical trials, and 5) Statistical Principles in Medical Research. The very substantial research, educational, and clinical resources of the Harvard Digestive Diseases Center, Harvard School of Public Health and the BIDMC Gastroenterology Division will be committed to the applicant to ensure successful attainment of the goals of this award.

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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 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

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Project Title: MICROARRAY-BASED STUDY OF IMMUNE RESPONSE IN IBD Principal Investigator & Institution: Dieckgraefe, Brian K.; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 29-SEP-2003 Summary: (adapted from applicant's abstract): Ulcerative colitis and Crohn's disease, chronic relapsing inflammatory disorders of the gastrointestinal tract, affect an estimated one million individuals in the United States. The cause or causes of these debilitating diseases remain unknown. Progress in our understanding and treatment of inflammatory bowel disease (IBD) remains slowed by our limited knowledge of gene products involved in disease pathogenesis and disease heterogeneity. Identification of markers for the precise characterization of patient subgroups and the identification of

42 Crohn’s Disease

those factors involved in the initiation, amplification, and perpetuation of the chronic immune response are priority objectives for future inflammatory bowel disease research. The immune response in inflammatory bowel disease is accompanied by complex changes in mucosal gene expression, including expression of molecules related to cell recruitment, adhesion, cellular activation and differentiation, expression of immunomodulatory molecules like cytokines or chemokines, and molecules involved in tissue remodeling and repair. Genome-wide sequencing projects and the development of microarray techniques have recently provided us with new methods that can provide a global perspective on these mucosal events and permit direct investigation of the gene expression resulting in the inflammatory phenotype. We propose to use microarrays derived from the normalized and well- characterized disease-specific libraries we have constructed to examine the following hypothesis: Analysis of genome-wide mucosal gene expression patterns will identify gene clusters or "signatures" which distinguish different inflammatory bowel disease groups, reflective of the differences in the underlying genetic and environmental pathogenesis. Genes contained within these clusters will serve as markers for the involvement of specific cellular processes or expression of key immunoregulatory molecules. To begin to address this hypothesis, we will focus our efforts on two specific aims: (1) using disease-specific cDNA microarrays, we will characterize the genome-wide mucosal gene expression in patient groups with presentations of inflammatory bowel disease reflective of the diverse clinical patterns. We will investigate the application of microarrays, using cell-type, activation, and differentiation-specific markers as a method to precisely characterize changes in individual leukocyte populations in the inflammatory mucosa; and (2) we will develop, validate, and apply techniques for utilization of endoscopic biopsy samples as input for gene array analysis. We will also apply microarrays to large, well-characterized groups of IBD patients and apply new data analysis tools to identify gene expression signatures on the array for associations with specific pathologic or clinical phenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROBIAL ANTIGENS IN CROHN'S DISEASE Principal Investigator & Institution: Braun, Jonathan; Professor & Chair; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001 Summary: Immune mechanisms of Pathogenesis and Protection for Crohn's Disease Candidate Microbial Antigens. Commensal bacteria are an important disease factor in human Crohn's disease and murine IBD models. This insight raises two critical issues for emerging research: Is immune pathogenesis of CD mediated by responses to particular enteric microorganisms? And, Can these responses by manipulated to yield now- inflammatory or anti-inflammatory immunity. In the previous grant period, our laboratory successfully applied immunologic and subtractive cloning approaches identify a set of bacterial species and microbial antigens associated with UC and CD. This renewal application focuses on one of these candidates, I2, a novel gene of bacterial origin found to be localized in CD lesions. Recombinant expression of the I2-encoded protein revealed highly disease-specific antibody levels in human CD. In the mouse, native memory T cell immunity to I2 was demonstrated, and the effector profiles were polarized to TH1 and TH2 in colitis susceptible and resistant mouse strains, respectively. These finding support the bacterium as a candidate pathogen in CD, and present the unique opportunity to evaluate the microbiology and immune response for a candidate human CD pathogen in laboratory mouse strains. Our renewal project tests two hypotheses. First, we predict that the I2 bacterium exemplifies one of the subset of

Studies 43

microorganisms pathogenic in Crohn's disease, due to its capacity to colonize relevant mucosal sites and elicit a local tissue-destructive mucosal sites and elicit a local tissuedestructive immune response in susceptible hosts. We will experimentally approach this hypothesis by isolating and characterizing the I2 bacterium with regard to taxonomy, virulence traits, and intestinal tissue distribution. From an immunologic perspective, we will evaluate the peptide specificity, ontogeny, anatomic origin, and pathogenicity of T cell populations and cell lines specific for the I2 antigen. Second, we predict that this or other antigen commensal microorganisms and mucosal autoantigens are targets of antiinflammatory T cells necessary for the natural and therapeutic protection to colitis. We will experimentally test this hypothesis by characterizing the ontogeny and localization of these T cell populations; isolating antigen-specific anti-inflammatory T cell populations and evaluating their protective effect in colitis transfer models; and, testing antigen-transfer strategies as therapeutic immunomodulators of model colitis. These aims will depend on shared studies with Project 4 (cellular and topologic development of pathogenic and protective mucosal T cell populations in the mouse), Project 2 ( characterization of human B and T cell clonal populations specific for Project 3-derived microbial antigens), and Project 1( human genetic loci associated with these antimicrobial responses). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Rojas-Cartagena, Carmencita; Microbiology; Ponce School of Medicine G.P.O. Box 7004 Ponce, PR 00731 Timing: Fiscal Year 2002; Project Start 20-MAR-2003 Summary: (provided by applicant): Endometriosis is a disorder characterized by the presence of histologically normal endometrial tissue outside the uterus. Endometriosis often presents with symptoms that mimic gastrointestinal disorders such as Crohn's disease, which makes it's diagnosis extremely difficult. Both disease produce similar symptoms, and their pathogenesis still remains to be elucidated. The objective of this study is to elucidate the the role of TNF/TNFR expression in rats models of intestinal endometriosis and Crohn's disease. The proposed rat model of Crohn's disease has been extensively used to study the pathophysiology of this disease. The rat model of intestinal endometriosis wil specfically address the pathopysiological role of TNF/TNFR expression in the implantation of ectopic endometrium in the intestine. The specific aims of the proposed plan are to: 1)determine the TNF'-aipha mRNA and protein expression in the implants, intestine, and peritoneal fluid in a rat model of intestinal endometriosis and compare with the rat model of Crohn's disease 2) determine the expression on TNF receptors (TNFR1/TNFR2) in the endometrial implants and associated intestine in a rat model of intestinal endometriosis and compare with the rat model of Crohn's disease 3) determine the expression of tumor necrosis factor receptor-associated factors (TRAFs) in both animals models and, 4) establish a specific pathophysiological role of TNF/TNFR signaling for the rat model of intestinal endometriosis and the rat model of Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR ADAPTATION

&

CELLULAR

ANALYSIS

OF

INTESTINAL

Principal Investigator & Institution: Rubin, Deborah C.; Associate Professor of Medicine; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, MO 63110

44 Crohn’s Disease

Timing: Fiscal Year 2002; Project Start 18-SEP-1995; Project End 28-FEB-2007 Summary: (provided by applicant): Following loss of functional small bowel surface area, the intestinal epithelium mounts a remarkable adaptive response, with enhanced crypt cell proliferation and epithelial cell migration, increased villus height, crypt depth and nutrient absorption. This precisely balanced process of proliferation and differentiation is established and maintained by interactions between the epithelium and mesenchymal components such as intestinal myofibroblasts that surround the crypt. Studies proposed in this renewal will continue to use rodent models of intestinal adaptation following small bowel resection to study fundamental mechanisms of gut epithelial cell proliferation and differentiation. During the current project period, two genes that are markedly regulated during the early phase of the intestinal adaptive response, PC4/TIS7 and epimorphin, were shown to have profound effects on morphogenesis and differentiation of the epithelium. The major hypotheses of the current proposal are: 1) PC4/TIS7 plays a key role in growth regulation and terminal differentiation in gut epithelial cells, 2) Epimorphin produced by intestinal myofibroblasts regulates the formation and maintenance of the crypt-villus axis. To address these hypotheses, the Specific Aims are: 1) Continue an analysis of PC4/TIS7 function and regulation in intestinal epithelial cells, 2) Determine the in vivo function of PC4/TIS7, using transgenic mice, 3) Determine the mechanism(s) by which epimorphin/syntaxin 2 induces crypt-villus morphogenesis and cytodifferentiation, 4) Determine the in vivo function of epimorphin. These studies are significant because they will enhance our understanding the molecular regulation of the adaptive response and this knowledge will facilitate designing specific clinical regimens for short bowel syndrome and for diseases such as Crohn's disease, that are characterized by intestinal epithelial injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ANALYSIS OF MICROBES IN CHRONIC BOWEL DISEASE Principal Investigator & Institution: Pace, Norman R.; Professor; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, CO 80309 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): This proposed research program will determine the microbial constituents of tissues associated with inflammatory bowel diseases (IBD), in both human and animal systems, in order to identify microbes associated with the disease-states. The human inflammatory bowel diseases, ulcerative colitis (UC) and Crohn’s disease (CD), are chronic, devastating diseases of unknown etiology. It is possible that microorganisms, perhaps indigenous and so far undiscovered, participate in the disease process. Although some evidence suggests that Mycobacterium avium ssp. paratuberculosis (MAP) may be involved in CD, microbiological analyses have been critically compromised by the clinical need to culture unknown organisms in order to detect and identify them. Culture techniques are frequently ineffective and usually underestimate the true diversity of microbes in natural samples. The phylogenetic analysis of ribosomal RNA (rRNA) genes, amplified from mixed community genomic DNA (e.g. host plus associated microbiota) by polymerase chain reaction, allows species identification in the absence of cultivation. We propose to analyze the microbial communities of both human IBD and normal gastrointestinal samples by this rRNA gene-based technology in order to identify and characterize candidate microbial etiological agents of IBD. The results of molecular studies will guide directed attempts to culture suspected pathogens, including MAP, from diseased tissues. Parallel analyses

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of animal IBD models, including bovine Johne?s disease and rodent models of IBD, will be conducted in order to validate the molecular-phylogenetic strategy, provide insight into microbial involvement in IBD pathogenesis, and guide the choice of appropriate tissues to be analyzed in human IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ANALYSIS OF TIGHT JUNCTIONS IN LIVER AND GUT Principal Investigator & Institution: Anderson, James A.; Professor; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 01-FEB-1992; Project End 30-JUN-2008 Summary: (provided by applicant): The long-range goal of this project is to understand the molecular basis for regulating paracellular transport of solutes across the tight junctions of epithelia in the gastrointestinal tract and liver. Barrier characteristics of tight junctions vary widely among cell types in terms of electrical resistance, solute flux and ionic charge selectivity. When the barrier is disrupted by pathogenic factors in different tissues (inflammation, specific bacterial toxins, drugs, etc.) transport is arrested leading to diarrhea, cholestasis, or enhanced entry of antigens and microbes. Presently the molecular basis for the barrier, its variable properties and regulation are poorly understood. In the proposed studies we will pursue the hypothesis that a newly described family of transmembrane proteins called the claudins are responsible for forming the barrier and its selectivity properties. First, we will examine whether selected members of the 20 claudins show different immunohistochemical location among different cell types of the GI tract. We will determine in human tissues whether the expression levels and patterns change in the colon and small bowel in response to cancer and inflammation. Differential expression patterns and responses will be considered consistent with a role in providing the junction's variable properties. Second, we will directly test the ability of individual claudins to alter barrier properties such as electrical resistance, solute flux and ion selectivity when expressed in cultured epithelial cells. We will attempt to define the protein sequences involving in creating the barrier's variable properties through site-directed mutageneis of the extracellular sequences. Third, we will define the protein structural basis for the barrier by determining the oligomeric state of claudins solubilized from membranes into non-ionic detergents using biochemical and biophysical methods and chemical cross linking. We will determine whether the basic protein unit of the barrier is homo- or heteromeric and attempt direct structural analysis using cryo-electron microscopy. This will allow us to see how the proteins fold and contact to create a selective barrier. Structural information will be correlated with the physiologic and mutagenesis studies. The physiologic and structural properties of a second Tight Junction transmembrane protein occludin, will be compared with the claudins. Together these studies will provide significant and novel advancements in our understanding of how paracellular transport is regulated and is altered in disease Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR PARATUBERCULOSIS

DEFINITION

OF

Principal Investigator & Institution: Inamine, Julia M.; Microbiology; Colorado State University Fort Collins, CO 80523

MYCOBACTERIUM Associate

Professor;

46 Crohn’s Disease

Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): This proposal is in response to RFA AI- 01-004 "Infectious Etiology of Chronic Diseases: Novel Approaches to Pathogen Detection" and specifically addresses the study of Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis). M. paratuberculosis is the etiological agent of Johne's disease, chronic granulomatous enteritis in cattle and other ruminants, and has been implicated as a possible cause of Crohn's disease in humans. The difficulty in confirming or refuting an etiological link between M. paratuberculosis and Crohn's disease is a reflection of two issues associated with M. paratuberculosis: 1) the very slow growth of the bacterium engenders a long incubation period in the host and hinders detection; and 2) there is a poor understanding of the biochemistry and genetics of this organism. It is our contention that the second issue can be best addressed by a molecular definition of M. paratuberculosis. This goal will be accomplished by four specific aims: 1) use standard proteomic methods and develop a new ICAT- based method to identify M. paratuberculosis-specific gene expression; 2) perform genomic analyses by using Suppression Subtractive Hybridization to identify M. paratuberculosis-specific sequences; 3) characterize the polysaccharides, lipoglycans and lipids expressed by M. paratuberculosis to provide a complete biochemical analysis that will assist in defining chemical markers for this organism; and 4) develop a proteome website and a reagent repository (including recombinant M. paratuberculosis-specific proteins and clinical isolates) as a service to other basic researchers and clinicians. We will employ the strategies that are currently used by the Mycobacteria Research Laboratories at Colorado State University to support tuberculosis and leprosy research throughout the world to provide a rapid and economic means to obtain information required to develop new diagnostics and vaccines, and elucidate the biochemical and genomic differences that allow M. paratuberculosis to maintain a specific biological niche that is not shared by the closely related M. avium subspecies avium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUCOSAL T-CELLS IN EARLY&LATE PEDIATRIC CROHN'S DISEASE Principal Investigator & Institution: Kugathasan, Subra; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: PROPOSAL (Adapted from the applicant's abstract): The overall goal of this project is to functionally and phenotypically characterize gut mucosal T-cells in children with new onset as well as longstanding Crohn's disease (CD), and use this information in guiding the development of new strategies for CD diagnosis, patient substratification and early medical intervention. CD is a devastating lifelong chronic inflammatory destruction of the gastrointestional tract that is most frequently diagnosed in adolescents and young adults. Because the cause of CD remains undefined, diagnosis relies on the identification of destructive mucosal changes identified on x-ray, endoscopy and/or tissue histology. Recent clinical trials suggest that early immunomodulator therapy results in an improved clinical outcome in CD children, but early medical intervention may be hindered by a lag in diagnosis of up to 18 months. Basic investigation also suggests significant differences exist in cellular and molecular mechanisms between "early" and "late" phases of chronic inflammation in the intestine, further emphasizing the need for investigation both at the time of diagnosis as well as in longstanding CD. Over the past four years, the investigators have conducted a systematic investigation of mucosal T-cells isolated from endoscopic biopsies in children

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with CD as well as non-inflammatory bowel disease (IBD) inflammation and normal controls. They have defined unique patterns of in vitro T-cell growth and proliferation in response to interleukin-2 (IL-2), where CD, mucosal T- cells demonstrate significantly enhanced in vitro growth (J. Peds., 133: 675- 81, 1998). Recent flow cytometric analysis of mucosal T-cell phenotype has shown that markers of immunologic memory (CD45RA, CD45RO) and homing (L- selectin) differentiate "early" and "late" phases of chronic inflammation in CD children. Thus, the central hypothesis of this proposal is: Characterization of mucosal T-cell function and phenotype will allow for prompt diagnosis as well as substratification into "early" and "late" phases of chronic inflammation in pediatric CD. This hypothesis will be tested with the following three specific aims. Aim 1 is the characterization of mucosal T-cell in vitro growth in the early diagnosis of CD, with cross-sectional validation, longitudinal follow-up, and evaluation of children at risk. Aim 2 is the characterization of mucosal T-cell phenotype and function during early and late CD with analysis of mucosal T-cell subsets and cytokine production. Aim 3 is to assess the impact of early immunomodulatory therapy on clinical outcome and correlate with mucosal T-cell phenotype and function in newly diagnosed CD patients over a 24-month longitudinal follow-up. Thus, the K23 Mentored Patient-Oriented Clinical Research Career Development Award will not only define fundamental areas of immunopathogenesis in the under-researched area of pediatric CD, it will also allow the applicant to obtain critical training and expertise required to perform high caliber translational research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTI-SITE TRIAL OF AZATHIOPRINE DOSING IN CROHN DISEASE Principal Investigator & Institution: Hanauer, Stephen B.; Professor of Medicine; Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2007 Summary: (provided by applicant): Azathioprine (AZA) is an effective steroid-sparing therapy for chronically active Crohn's Disease (CD) and prevents relapse of steroidinduced remissions. However, despite efficacy in controlled trials, there is no doseranging data or prospective evidence on how to optimize therapy. It is now recognized that AZA, an inactive pro-drug, undergoes a series of enzymatic reactions leading to 6thioguanine nucleotides (6- TGN), considered the active but, myelotoxic, metabolites. In a competing enzymatic pathway, thiopurine methyltransferase (TPMT) catalyzes formation of 6-methyl-mercaptopurine ribonucleotides (6-MMPR), metabolites that are therapeutically inactive and potentially hepatotoxic. Co-dominantly inherited polymorphic alleles confer high (TPMTH) and low (TPMTL) functional TPMT activity that impact AZA's therapeutic response and toxicity. Retrospective observations suggest that low levels of 6-TGN metabolites (due to under-dosing or high TPMT activity) are associated with poor therapeutic response. The study hypotheses are that pharmacogenetic variability in the metabolism of AZA impacts short and long-term therapeutic efficacy and tolerance in the treatment of CD, and that optimal dosing and response to treatment can be predicted based upon baseline TPMT activity and early metabolite levels after initial dose-escalation. Our objective is to determine optimal dosing and prediction of response by prospectively assessing TPMT enzyme activity levels and serial 6-TGN measurements for the management of steroid refractory and steroid-dependent CD in adults and children. To test the hypothesis, we propose a double blind, multi-center trial randomizing adult and pediatric patients with steroidrefractory and steroid dependent CD to either current standard AZA therapy dosed at

48 Crohn’s Disease

2.5mg/kg, or AZA, at a dose determined by their TPMT activity, and subsequently adjusted to maintain the 6-TGN levels within the proposed therapeutic range. Our primary endpoint will be to determine if there is a difference between fixed and individualized AZA therapy in the frequency of steroid-free disease remissions at 16 weeks. Secondary endpoints will be to assess the frequencies of remissions at 28 weeks and 52 weeks and to assess adverse events, corticosteroid requirements, and health related quality of life endpoints. Predictive models will be performed to assess responsiveness based upon initial and inducible TPMT activity and achievable 6-TGN and 6-MMPR metabolite based upon incremental AZA dosing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYCOBACTERIUM AVIUM SUBSPECIES IN CROHN'S DISEASE Principal Investigator & Institution: Naser, Saleh A.; Molecular Biol & Microbiology; University of Central Florida 4000 Central Florida Blvd Orlando, FL 32816 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Crohn's disease (CD) is a debilitating chronic inflammatory bowel disease characterized by patches of inflamed tissue. The underlining cause of inflammation and provocation of the immune response in CD patients has yet to be determined. In theory, the immune system usually reacts against an invading organism such as an insect bite or bacterial infection, or is over-sensitive, as in allergic reactions to grass pollen etc. These reactions cause irritation and pain in the affected area, which subside when the immune system has dealt with the potential threat. Defects in the immune system of CD patients have been reported, both in the ability of the cell to phagocytose and in immune killing after phagocytosis, The cytokine pattern in CD is Th1-like and defect in the ratio of proinflammatory to anti- inflammatory cytokines has been proposed. A specific antigenic stimuli has not been identified, but pathogenic bacteria such as Mycobacterium avium subsp paratuberculosis (MAP) and specific invasive E. coli strains have been proposed. In addition, autoantibodies derived from molecular mimicry from bacterial antigens, or from host origin may also be causative agents of the inflammatory lesions in CD. Defects in the ability of macrophages to present antigen to T-cells and B-cells may also have a role. The mycobacterial theory is based on the significant similarity between CD and Johne's disease, a chronic enteritis in cattle that is caused by MAP. The two diseases share histological and pathological characteristics similar to those in tuberculosis and sarcoidosis. It is believed that MAP may be causing an immune reaction in the gut, resulting in a continuous immune response, which gets better and worse as the number of bacteria increase and decrease. Another possibility is that some parts of MAP like the heat shock proteins similar to parts of the gut lining resulting in triggering an immune response: a process known as autoimmunity. Finally, there may be defects in the immune reaction to MAP or proteins in the gut. In this case, the immune cells fail to deal with the invading organism, which is able to persist in the tissues, causing further inflammation. Many studies have been performed in an attempt to investigate a mycobacterial role in the etiology of CD and its pathogenesis. The outcome has been inconsistent which has added to the controversy. The role of MAP, if any, in the etiology of CD has become increasingly debated in recent years causing a need for clear elucidation. While positive results would change the course of therapy and investigation in CD, a negative result will go a long way toward clearing up the MAP debate. In this study, our team will investigate the overall role of MAP, if any, in CD etiology by addressing the following questions: Is MAP present in CD lesions? Is it culturable? Can MAP be identified using PCR, RT-PCR or fluorescence in situ hybridization (FISH) techniques? Is there any immune reaction activity against MAP in

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CD patients? Is it cellular, humoral or both? What types of immune cells are present in CD lesions compared to non-inflammatory tissue or tissue from non-IBD and healthy controls? Are there any abnormalities in bacterial phagocytosis by peripheral blood monocytes and neutrophils from CD patients compared to normal cells? Are there factors inhibitory to phagocytosis in CD serum? Are there any abnormalities in antigen presentation and lymphocyte transformation to recall antigens from MAP? Are there any inhibitory or augmenting factors present in the serum from CD patients (cellular and serum crossover)? Our approach in this project is to determine if MAP or reactions against MAP are present in full thickness surgical tissue, heparinized blood and sera specimens from patients with CD using well-developed methodology in the fields of microbiology, immunology and molecular microbiology. We will investigate the presence of MAP in tissue specimens directly by using nested PCR, RT-PCR and FISH and indirectly by culture using a newly developed culture media appropriate for isolation of cell wall deficient form of MAP. We will also investigate the humoral immune reaction in CD sera using p20 antigen, a MAP specific protein. Additionally, the type and state of immune cells will be determined in inflamed versus non-inflamed tissue specimens from CD patients. We will also examine how these cells from CD patient blood are able to ingest and kill MAP, and whether this ingestion results in a normal immune response. This is the first study designed to comprehensively examine the overall presence/absence of MAP in CD tissue and the immune response in CD patients. The results will give us a better idea as to whether MAP causes CD, or whether there is an inherent defect in the immune system, which allows bacterial persistence or autoimmunity to occur in the gut. Ultimately, the outcome of this study will go a long way toward clearing up the MAP debate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOD2 EXPRESSION IN EXPERIMENTAL CROHN'S DISEASE Principal Investigator & Institution: Wang, Pin; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2003; Project Start 01-JUN-2004 Summary: (provided by applicant): The aim of this project is to evaluate the role of the first Crohn's disease (CD) susceptibility gene, NOD2 in the development of chronic intestinal inflammation. There is increasing evidence that NOD2 is involved in the pathogenesis of CD from human CD susceptibility gene mapping studies and clinical genetic studies. Recent studies suggest that NOD2 expression is regulated by LPS and TNF, and NOD2 may sense bacterial LPS and activate NF-kB. Our lab has a mouse model (SAMP1/YitFc) of spontaneous chronic ileitis, which shares many features of human CD. This model provide us with a unique opportunity to investigate the abnormal expression of NOD2 in the development of chronic inflammation. To investigate NOD2 gene, first, the localization, distribution and half-life of NOD2 protein will be determined. Second, the magnitude and kinetics of NOD2 expression will be characterized at mRNA and protein levels in SAMP1/YitFc mice at different ages during the development of ileitis. Finally, the expression of Th1 cytokines and NF-kB associated genes will be explored in parallel with NOD2 expression. The overall objective of this project is to understand the function of NOD2 and associated inflammatory genes that may play a significant role in the development of Crohn's disease in order to prevent and treat this devastating disease more effectively. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOD2: A SUSCEPTIBILITY GENE FOR CROHN'S DISEASE Principal Investigator & Institution: Nunez, Gabriel; Professor; Pathology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 08-APR-2002; Project End 31-MAR-2007 Summary: The idiopathic inflammatory bowel diseases (IBD) which includes Crohn's disease and ulcerative colitis are chronic disorders of the gastrointestinal tract of unknown etiology with a combined prevalence of about 150-200 cases per 100,000 in western countries. Although the etiology of IBD is unknown, a large body of evidence suggest that these diseases are multifactorial and likely caused by an abnormal inflammatory response directed against luminal and/or enteric microflora in a genetically susceptible host. However, the genetic basis for this abnormal inflammatory response to enteric bacteria is unknown. Genome-wide searches for IBD-susceptibility genes have resulted in the identification of several loci harboring potential predisposing genes for Crohn's disease. Of these, linkage to the pericentromeric region of chromosome 16 (IBD1 locus) has been replicated by several independent studies to confer susceptibility to disease. We have identified Nod2, a gene that encodes a protein with homology to plant disease resistance gene products, that is located in the peak region of linkage disequilibrium on chromosome 16. We have found that a frameshift mutation and genetic variants of Nod2 are highly associated with susceptibility to Crohn's disease by genetic analysis in multi-case disease families and case-control studies. Nod2 is expressed in monocytes and activates NF- kappaB. Significantly, wildtype Nod2 confers responsiveness to bacterial lipopolysaccharides and this activity is deficient in mutant-Nod2 associated with Crohn's disease. These observations suggest a link between an innate immunity pathway controlled : byNod2 and susceptibility to Crohn's disesase. Our overall hypothesis is that Nod2 recognizes lipopolysaccharidesin the cytosol and activates a NF-kappaB signaling pathway in the host cell that protects the host against entericbacteria. Our preliminary results suggest a model in which deficiency in the Nod2 pathway leads to an abnormal T cell-mediated response to enteric bacteria and tissue destruction. We propose three Specific Aims to explore our hypothesis: (i) Determine the sequence of Nod2 that mediates functional activity and - recognition of bacterial LPS. The analyses will include study of Nod2 variants associated with Crohn's disease and systematic mutagenesis of Nod2; (ii) Determine the structure of LPS recognized by Nod2 and (iii) Characterize mice deficient in Nod2 to determine its role in the response to luminal and pathogenic enteric bacteria. The proposed studies should improve our understanding of the role of Nod2 in innate immunity and provideimportant insight into the link between genetic variation in Nod2 and susceptibility to Crohn's disease. The studies may lead to novel therapeutic approaches for Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OPEN LABEL TRIAL OF THALIDOMIDE IN TREATMENT OF REFRACTORY CROHNS DISEASE Principal Investigator & Institution: Ehrenpreis, Eli D.; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORAL AZATHIOPRINE IN CROHN'S DISEASE--IV AZATHIOPRINE Principal Investigator & Institution: Cuffari, Carmelo; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: Azathioprine is well known for its immunosuppressive properties in the treatment of recalcitrant Inflammatory Bowel Disease (IBD). It has been shown to eliminate the need for corticosteroids in about 75% of patients with Crohn's disease with a median response time of 16 weeks. Although azathioprine has proven clinical efficacy, physicians have been reluctant to use this immune modifying agent in the treatment of severe active disease on account of the delayed clinical response times. The delayed clinical response observed in patients on azathioprine therapy may be due in part to the drug's poor oral bioavailability. Indeed, the bioavailability of oral azathioprine ranges from 5-037%, and may explain why steady-state drug levels can only be obtained after 2 months of chronic therapy. A recent pilot study from the Mayo clinic has achieved improved clinical response times in their patients with severe active Crohn's disease with their use of intravenous therapy. This study suggests that intravenous therapy may improve clinical response time through improved drug bioavailability. This study will compare high dose intravenous azathioprine followed by oral azathioprine with conventional oral azathioprine alone in the treatment of Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OTHER CANCERS IN FAMILIES OF WILMS TUMOR PATIENTS: NEOPLASM & SYNDROMES Principal Investigator & Institution: Olson, Jane M.; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Crohn's disease and ulcerative colitis constitute the major forms of chronic inflammatory bowel diseases. These disorders occur in young adults with an estimated prevalence of more than 1/1000 inhabitants in western countries. Last year, our group reported a significant linkage of Crohn's disease to pericontromeric chromosome 16. This finding has since been replicated by four independent groups. A new European collaborative group has just been established to continue and expand the collection of Crohn's disease families from several European countries. These new families will assist current efforts to perform fine mapping of the chromosome 16 region and ultimately to isolate this gene. This large collection of families will also be used in further efforts to locate genes conferring susceptibility to Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF CHRONIC BOWEL DISEASE Principal Investigator & Institution: Carding, Simon R.; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001 Summary: The long term goal of this project is to understand the cause of inflammatory bowel disease (IBD). This is a complex group of idiopathic chronic inflammatory disorders of which Crohn's disease (CD) and ulcerative colitis (UC) are the major forms. A simple explanation for the cause of IBD has yet to emerge. Several of the immunologic and pathological features of UC can, however, be explained as a consequence of

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persistent T lymphocyte (T cell) activation in the gut that results in the production of inflammatory cytokines that direct or indirectly promote chronic inflammation and tissue injury. Progress in understanding the pathogenesis of IBD is restricted by the lack of suitable animal models. Of the animal models of IBD that have been described, the causal factors, pathology and clinical spectrum of colitis that spontaneously occurs in interleukin-2-deficient (IL-2-/-) mice most closely resembles that of human UC. The IL2-/- mouse is, therefore, one of the most promising animal model in which to investigate the immunopathogenesis of IBD. The purpose of the studies described in this proposal is, therefore, to determine the cause(s) of colitis in the IL-2-/- mouse which may provide new insights into the underlying causes of IBD in humans. The guiding hypothesis for these studies is that colitis is a consequence of the activity of abnormal mucosal T cell responses to normal enteric (gut bacteria) antigenic stimuli. Our studies to experimentally test this hypothesis have three specific aims. THE FIRST is to identify the T cell populations responsible for disease. This will be investigated by determining which populations of T cells present in IL-2-/- mice can, after adoptive transfer to otherwise normal healthy animals, cause disease. THE SECOND AIM is to determine if oral tolerance is intact in IL- 2-/- mice, and the nature of the antigenic stimuli that activates pathogenic T cells. Two approaches will be taken, (a) IL-2-/- mice will be crossed with T cell receptor (TCR) transgenic mice in which the majority of CD4 or CF8 T cells are specific for a defined antigen to determine if generation of the function gut T cell repertoire is normal, and if tolerance is maintained upon exposure to antigen in the gut in the absence of IL2 and, (b) germ free IL-2-/- mice will be conventionalized with members of the normal bacterial gut flora to determine if "oral tolerance" is intact and, if not, which bacteria can prime mucosal immune responses that initiate an inflammatory immune responses that results in colitis. THE THIRD AIM is to investigate how T cells cause epithelial cell injury. The possibility that T cells from IL-2-/- mice can disrupt epithelial cell growth as a result of cell-mediated cytotoxicity or, through the production of toxic or inflammatory cytokines will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ANTI TNF Principal Investigator & Institution: Vasiliauskas, Eric; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, CA 90502 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHYSIOLOGICAL REGULATION OF INTESTINAL PERMEABILITY Principal Investigator & Institution: Turner, Jerrold R.; Assistant Professor; Pathology; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 29-SEP-2001; Project End 31-AUG-2006 Summary: The intestinal mucosa maintains barrier function while allowing paracellular absorption of water and small nutrients. These opposing functions are balanced by the tight junction (TJ), which regulates paracellular permeability. The goal of this proposal is to elucidate molecular mechanisms that mediate TJ regulation in intestinal epithelium. Previous studies in isolated mammalian small intestinal mucosa and intact animals have shown that TJ permeability can be physiologically regulated by apical Na+-glucose cotransport. During the K08 award we have established a novel in vitro model of TJ regulation in the Caco-2 enterocyte-like cell line. This system was used to demonstrate

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that initiation of Na+-glucose cotransport causes increased TJ permeability. This led to the hypothesis that perijunctional actomyosin contraction is an intermediate in physiological TJ regulation. Evaluation of myosin II regulatory light chain (MLC) phosphorylation, a biochemical marker of actomyosin contraction, confirmed that MLC phosphorylation is necessary for this TJ regulation. The data also show that Na+-glucose cotransport activates the brush border Na+-H+ exchanger NHE3 and that inhibition of NHE3 decreases both MLC phosphorylation and TJ permeability, suggesting a common signaling pathway. Thus, the hypothesis that initiation of Na+-glucose cotransport triggers a signaling cascade that, in sequence, leads to i) NHE3 activation, ii) cytoplasmic alkalinization, iii) increased intestinal epithelial MLC kinase activity, iv) increased MLC phosphorylation, v) perijunctional actomyosin contraction, and vi) increased TJ permeability was developed. The first specific aim will focus on events that occur immediately after initiation of Na+-glucose cotransport and lead to NHE3 activation and cytoplasmic alkalinization. This will include evaluation of kinase pathways, intracellular Ca2+ and pH, and NHE3 activation. The second specific aim will concentrate on characterization of MLC kinase and its regulation. Finally, the third specific aim will use a regulated expression system to trigger MLC phosphorylation independent of proximal events, thereby allowing evaluation of structural and functional cytoskeletal and TJ modifications that follow MLC phosphorylation. These studies will provide mechanistic insight into signaling pathways that follow Na+nutrient cotransport and cause increased paracellular permeability. These studies may also provide detailed understanding of mechanisms of altered intestinal permeability in a wide range of human diseases, from Crohn's disease to infectious enteritis, and provide targets for novel therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PPARS: TRANSCRIPTIONAL REGULATORS OF METABOLISM Principal Investigator & Institution: Evans, Ronald M.; Senior Member; Keystone Symposia Drawer 1630, 221 Summit Pl #272 Silverthorne, CO 80498 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2003 Summary: (provided by applicant): Academic, pharmaceutical and clinical studies on the PPARs have been increasing at an exponential rate. The PPARs include a group of three related nuclear hormone receptors, (alpha, beta, and gamma) that have been implicated in many aspects of metabolic disease, particularly in the development of adult onset (Type II) diabetes, obesity, hypertension, and atherosclerosis. These receptors are also seen as potential therapeutic targets in the treatment of inflammatory bowel disease, Crohn's disease, colon cancer, prostate cancer and breast cancer. Of prominent interest for the upcoming meeting are: 1) defining the roles of the PPARs in various physiological and pathological settings such as diabetes, cardiovascular disease and immune cell function. 2) Identifying new ligands, both biological and synthetic that will help open new avenues of investigation and therapeutic intervention. 3) Define longterm benefits and risks of PPAR active drugs, including Actos, Avandia and the fibrates. 4) Identifying new coactivator/repressor proteins and in particular, determining which of these components are associated with specific biological programs. 5) Developing specific molecular links between the PPARs and other nuclear receptors including LXR, FXR, and PXR. These orphan receptors help to coordinate metabolic function and may act in a cascade fashion to impact on PPAR action. This meeting will bring together experts from the pharmaceutical, academic and biotechnology industries. Although the PPARs are routinely discussed at meetings focused on nuclear receptors, diabetes, obesity or gene transcription, this conference

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promotes a unique confluence of all of these areas by bringing in experts who approach the field with differing backgrounds and interests. It is believed that this synergy will push this exciting field forward at an accelerated pace. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREDISPOSING GENES IN MURINE ILEITIS Principal Investigator & Institution: Mcduffie, Marcia J.; Associate Professor; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001 Summary: Susceptibility to inflammatory bowel diseases (IBD) in human populations appears to have a significant heritable component. Modeling based on relative genetic risk data from family and population studies predicts that such susceptibility is multigenic and that disease expression is influenced significantly by environmental factors which are, as yet, undefined. In the absence of a mechanism for identifying candidate genes, genetic studies in humans are unlikely to be successful because of the size of the study populations required for successful random linkage analysis and the inability to control for environmental influences on disease expression. Such problems are limiting factors which cannot readily be solved using the resources available. An alternative approach to studying the genetic control of susceptibility to IBD makes use of rodent models. These models have the distinct advantages of short generation times, potential for controlled breeding, and standardization of environmental influences. As outlined in the overview for this program, the SAMP1/Yit mouse strain provides a unique resource for studying genetic contributions to disease susceptibility in a spontaneous model of ileitis. In contrast to the other rodent models of IBD, this inbred mouse strain develops destructive inflammation of the distal small bowel with many of the pathological and histological features of Crohn's disease (CD). Penetrance is extremely high (100% by 30 weeks of age), and we have shown that disease expression can be largely inhibited by outcross to C57BL/6 mice, demonstrating the genetic control of the disease process in these mice. In order to begin to identify the specific genes involved in the IBD of SAMP1/Yit mice, we propose the following specific aims: 1. To define the model of inheritance of spontaneous ileitis in SAMP1/Yit mice by outcross and backcross breeding with relevant inbred mouse strains. 2. To localize the genes required for disease expression by genome-wide scans of F2 and backcross progeny from these crosses using microsatellite genotyping. 3. To develop disease-resistant recombinant congenic mice using a "marker-assisted" selection strategy for functional characterization of ileitis susceptibility loci and the identification of interval-specific candidate genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QTL OF CROHN'S DISEASE ANTIBODIES Principal Investigator & Institution: Rotter, Jerome I.; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001 Summary: The overall goal of Project 1 is to bring a quantitative trait locus (QTL) linkage approach to the problem of identification of genes predisposing to subsets of Crohn's disease (CD). This approach, which is increasingly utilized to successfully elucidate the genetic basis of a number of complex diseases preserves the power of a genome wide scan but increases the power of identifying disease genes by utilizing a more homogenous sample for analysis. This Program Project, especially the interactions

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between Projects 1, 2, and 3, provides unique resources and expertise in quantitative antibody phenotyping, genetic epidemiology, and molecular genotyping that maximizes the power of this approach in IBD. This project takes advantage of data that we have developed in the current cycle: that the presence of antibodies to Saccharomyces cerevisiae (ASCA) identify a more homogeneous group of CD patients, that the distribution of ASCA is familial in both affected and unaffected CD family members, that ASCA levels are highly heritable and thus is an important trait which is likely to be successfully mapped in a linkage analysis, and that in preliminary analyses the quantitative trait of ASCA is linked to at least one gene region, the major histocompatibility complex (MHC) on the short arm of chromosome 6. We thus plan to proceed in parallel with two goals, a detailed evaluation of the MHC, and a two stage, two sample genome-wide scan for quantitative ASCA levels and other CD associated antibodies. The first Aim of this project is to identify the chromosomal regions contributing to the expression of ASCA by a 10 cM density genome-wide scan in 120 CD families (with over 1100 relative pairs) already sampled and demonstrated to have an ASCA positive proband. The second Aim will be to fine map to 2-3cM density the regions identified in Aim 1, with the goal of identifying those regions with the best evidence for linkage. Aim 3 will be to confirm these latter regions in a second independent sample of similar size. In Aim 4 we will proceed to candidate gene analyses in the linked regions. Aim 5 takes advantage of the preliminary data in the current cycle, to proceed to extremely fine mapping of genes in the MHC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUALITY OF LIFE IN PEDIATRIC INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Perrin, James M.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Measurement of the quality of life (QoL) of children and adolescents with inflammatory bowel diseases (IBD) has had little attention, despite the importance of understanding key factors affecting QoL, especially for measuring the effects of clinical trials to improve IBD outcomes. The main purpose of this pilot study is to examine the impact of clinical severity and treatment social factors on the quality of life (QoL) of a diverse population of children and adolescents with inflammatory bowel disease (IBD). Secondary purposes include determining the effects of sociodemographic factors on QoL and exploring the concordance of views of parents and children of QoL. The study aims are to 1) determine the associations of of clinical characteristics (condition type, activity/severity, and treatment) with specific components of general health-related quality of life and IBD-specific QoL; 2) describe the effects of sociodemographic characteristics (SES, age, and gender) on these measures; and 3) compare the views of different observers (parent and child with IBD) of the child's QoL. The study will apply both general and condition-specific QoL measures among a random sample of 250 children and adolescents with IBD, ages 5-18 years, in six clinical sites. We will obtain measures of QoL from both the child and a parent in each case. The study will obtain additional data regarding the subjects' clinical condition (condition type, severity/activity, treatment [including surgery], age of onset) and socioeconomic status (household structure and income). Main analyses will compare general and specific measures of QoL and examine the influence of clinical and sociodemographic variables on QoL, through multivariate regression techniques. We will also examine the differences in child and parent assessments of QoL. The information from this study will

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provide a stronger base for future studies of treatment and natural history of IBD. It will help to clarify the life domains that are affected by IBD and will inform interventions to improve QoL for children with IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GUT SUBSTANCE P RECEPTORS Principal Investigator & Institution: Vigna, Steven R.; Associate Professor; Medicine; Duke University Durham, NC 27706 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-DEC-2006 Summary: (provided by applicant): Substance P (SP) is a neuropeptide involved in physiological regulation and has also been implicated in the pathway resulting in pain and inflammation. In the previous funding period we showed that the SP neurokinin-1 receptor (NK-1R) desensitizes more rapidly and extensively than may other G proteincoupled receptor and that this is caused by receptor phosphorylation and is correlated with receptor-mediated physiological responses. In addition, we showed that the NK-1R undergoes vigorous agonist-dependent endocytosis and recycling as a primary mechanism of resensitization. We also showed that the NK-1R in the rat intestine mediates Clostridium difficile toxin A-induced inflammation, secretion, and tissue damage. These observations suggest that the NK-1R is highly regulated and plays a major role in intestinal inflammation, but the mechanisms of NK-1R regulation are incompletely understood. The current proposal describes studies designed to reveal additional mechanisms of NK-1R regulation. The proposed specific aims are to 1) test the hypothesis that the N-terminus of SP plays a role in homologous desensitization of the NK-1R even though the C-terminus contains all of the agonist activity of the peptide, 2) test the hypothesis that the cytoplasmic microfilament component of the cytoskeleton in NK-1R-expressing cells plays a role in SP-mediated signaling, and 3) test several hypotheses concerning the mechanisms of SP-stimulation of MAP Kinase activity via the NK-1R. These hypotheses will be tested by multiple approaches including assessment of NK-1R signaling and desensitization after site-directed NK-1R mutagenesis. These studies will lead to insight into the normal mechanisms of SP NK-1R regulation and will suggest possible mechanisms of abnormal NK-1R regulation in intestinal inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF T CELL RESPONSES IN IBD Principal Investigator & Institution: Terhorst, Cornelis P.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2002 Summary: (Adapted from applicant's abstract): Ulcerative colitis and Crohn's disease, collectively referred to as inflammatory bowel disease (IBD), are chronic, spontaneously relapsing disorders, which appear to be immunologically mediated and to have genetic and environmental components. The pathways that lead to these diseases were in principle dissected by using genetically well-defined animal models. The main objective of this proposal is to begin to translate the principles that the PI and others have established in studies of animal models to the human IBD. The major hypothesis is that two possible mechanisms exist for the presence of "Aggressor Th1 cells" in experimental colitis and therefore in human IBD. In one model the Polarized Th1 cells that are found in the lamina propria are induced to become aggressor Th1. In an alternative model the absence of regulatory cells (for instance Th1 cells, but not per

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exclusion of others) leads to the generation of the aggressor Tr1 cell. The two models most likely cooperate in the induction of pathogenesis of IBD. In this proposal the investigators seek to further dissect these functional subsets of human LPLs based upon two major hypotheses: (1) unique subsets of T lymphocytes exist within the LPL compartment these include regulatory T cells such as Tr1 cells; and (2) the function and frequency of regulatory T cells (Trl and CDld reactive NKT cells) is perturbed in IBD patients. We specifically proposes to: (1) define the role of SLAM/SAP system in controlling induction of IFN-gamma, IL-10 and TGF-beta genes by lamina propria lymphocytes; (2) test the hypothesis that human Tr1 cells regulate immune responses by lamina propria T lymphocytes from normal individuals, but not in patients with Ulcerative Colitis or Crohn's disease; and (3) test the hypothesis that human CD1-d reactive T cells regulate immune responses by lamina propria T lymphocytes, but not in patients with Ulcerative Colitis or Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF CHEMOKINES IN T CELL MEDIATED COLITIS Principal Investigator & Institution: Lillard, James W.; Assistant Professor; Microbiology and Immunology; Morehouse School of Medicine Atlanta, GA 30310 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Inflammatory bowel diseases (IBD) are chronic, relapsing and tissue destructive diseases. T helper type l (Thl) cells secreting TNF-alpha and IFN-gamma have been emphasized in ulcerative colitis, while Th2 cells may be more closely associated with Crohn's disease. However, either Thl or Th2 cells can induce colitis in several mouse models; hence the precise causes of these two forms of IBD are incompletely understood. It has recently been shown that the mechanisms of IBD involve antigen- dependent interactions between CD4+ T cells and antigen-presenting cells (APCs) as well as genetic factors. A major deficiency in understanding the steps responsible for IBD, is the lack of comprehension for the role innate and early acting factors play in mucosal immune responses. Chemokines are a family of proteins that are resistant to inactivation by pH or proteolysis as well as affect the chemotaxis and angiogenesis of leukocytes and endothelial cells. Therefore, chemokines no doubt play a pivotal role in the regulation (i.e., initiation, maintenance, and suppression) of mucosal inflammation and tissue destruction. In fact, human interleukin-8 (IL-8), IFN-gamma inducible protein - l0 (IP-l0), CXCR3 (the receptor for IP-10), RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted), and MCP-l/JE (monocyte chemotactic protein-1) have been shown to be unregulated at the sites of mucosal inflammation (IBD). The current proposal stems from our recent findings that RANTES, IP-10, IL- 8, lymphotactin (Lptn), but not MCP-l/JE, can enhance mucosal adaptive immune responses. Since these chemolcines act at several levels, four Specific Aims will be addressed to elucidate the precise role of these chemokines and their corresponding receptors in IBD. The first aim will define the regulatory role of chemokines that are secreted by CD45RBHI CD4+ T cells subsets, which cause experimental IBD after adoptive transfer. The second aim will assess the role of mIL-8Rh (murine IL- 8/GCP2 receptor), CCR5 (a RANTES receptor), CXCR3, and XCRl (Lptn receptor) interactions in the CD45RBHI CD4+ T cell transfer model of murine IBD. The third aim will evaluate the chemokines, cytokines, and corresponding receptors that are expressed by the IBD inducers (CD45RBHI) and IBD suppressors (CDRB45LO) CD4+ T cells subsets. The fourth aim will ascertain the angiogenic or angiostatic factors and cell signaling molecules that are expressed or activated, respectively, by chemokines that regulate IBD. These proposed studies will provide important and novel information regarding

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the cellular and molecular mechanisms that chemokines use to induce, maintain, and suppress mucosal inflammation and angiogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF IL 18 IN CROHN'S DISEASE Principal Investigator & Institution: Pizarro, Theresa T.; Assistant Professor of Medicine; Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: (Adapted from the applicant's abstract): Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affects more than one million people in North America. Increasing evidence suggests that an imbalance of Th1 / Th2 polarization, in favor of Th1 cell subsets, may be a key pathogenic mechanism in a variety of organ-specific autoimmune disease, such as IBD. In CD, evidence has accumulated from both animal models and human studies to indicate that Th1 cytokines are involved in the pathogenesis of this disorder. However, identification of the specific initiating factor(s) driving Th1-mediated immune responses represents an important issue. The present proposal focuses on IL-18, a newly described cytokine, primarily produced by macrophages and other non-immune cell types. Recent studies suggest that IL-18 may function as a "classic" proinflammatory cytokine by playing a primary role in Th1-mediated immune responses and strongly implicates IL-18 as a possible mediator of organ-specific autoimmune disease(s), including CD. Therefore, the central hypothesis of this proposal is that IL-18, having the ability to elicit Th1-polarized T cell responses, may play a crucial pathogenic role in CD, as well-defined prototypic Th1 disorder. The following four specific aims will be investigated to: 1) Characterize the expression of IL-18 in the intestinal mucosa of IBD patients. Using various techniques and at multiple levels, IL-18 mRNA and protein levels will be determined in tissues isolated from the intestines of IBD patients as well as inflammatory and normal controls (IC and NC, respectively). The results obtained from these studies will be compared to those from freshly isolated intestinal mucosal cells, including intestinal epithelial cells (IEC), lamina propria mononuclear cells (LPMC) and various mesenchymal cell populations. Finally, IL-18 expression will be correlated with disease severity as well as clinical phenotype of IBD subgroups. These studies, although descriptive, represent a fundamental step before pursuing more mechanistic studies described in the subsequent specific aims. 2) Determine the factor(s) regulating IL-18 production in, as well as the effects of IL-18 on, intestinal mucosal cells. The regulation of IL-18, in general, and in the context of intestinal inflammation, in particular, will be assessed by investigating the effects of several "classic" proinflammatory and Th1 cytokines on IL-18 expression in different gut mucosal cells. Furthermore, the effects of IL-18, itself, will be evaluated for its ability to activate the inflammatory response typical of CD in IEC, LPMC and intestinal mesenchymal cells by determining IL-18-induced transcription factor activation and subsequent cytokine profile expression. These experiments will reveal critical functions of IL-18 in regulating gut immune responses. 3) Determine the transcriptional regulation of the human IL-18 gene in different intestinal mucosal cell populations. Isolation of the human IL-18 gene, characterization of its structure and mapping of its transcriptional start sites(s) will be initially achieved in order to perform the analyses of IL-18 promoter activity. Promoter function studies will achieved the creation of reporter constructs, site mutagenesis experiments and transfection assays in different intestinal cells lines. These studies will define how the human IL-18 gene is regulated, particularly during gut inflammation, and if transcriptional control varies among different intestinal cell types. 4) Identify, and characterize the properties of, the

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31 kD putative IL-18 homologue predominantly found in intestinal epithelial cells. In order to identify the true nature of this putative IL-18 related protein, an expression cDNA phage library will be derived from IEC and immunoscreened for IL-18+ phage plaques. Purified isolates will be subsequently characterized for their unique features. These experiments will allow the discovery of novel IL-18 homologues and determine if they are differentially expressed in various cell types within the intestinal mucosa. The ultimate goal of the present research proposal is to define the precise role of IL-18 in CD in order to develop specific treatment modalities aimed at modifying the natural course of this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF THE ALPHA 1 BETA 1 INTEGRIN IN CHRONIC COLITIS Principal Investigator & Institution: Pavlick, Kevin P.; Molecular and Cellular Physio; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, LA 71103 Timing: Fiscal Year 2003; Project Start 31-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): The inflammatory bowel diseases (Crohn's disease, ulcerative colitis; IBD) are chronic idiopathic inflammatory disorders of the intestinal tract. IBD is characterized by the infiltration of large numbers of monocytes, lymphocytes, and neutrophils into the intestinal interstitium accompanied by extensive mucosal and/or transmural injury. Recent evidence suggests that interaction between collagen-binding integrins (e.g. alpha-1-beta-1) and the extracellular matrix promotes the migration and/or activation of leukocytes in different models of inflammation. However, relatively little information is available describing the importance of leukocyte-interstitial matrix interactions in chronic gut inflammation. Therefore, the overall objective of this study is to better understand the role of the alpha-1-beta-1 collagen-binding integrin in the pathophysiology of chronic gut inflammation in an immune-based murine model of chronic colitis. Hypothesis: We propose that T-cell and/or granulocyte-associated integrin alpha-1-beta-1 interacts with interstitial collagen in the colonic interstitium resulting in the activation of these cells with the upregulation of certain proinflammatory cytokines that may initiate and/or perpetuate chronic gut inflammation. In order to test this hypothesis we propose the following specific aims: 1) Evaluate the importance of T-lymphocyte alpha-1-beta-1 surface expression on the promotion of chronic gut inflammation using donor T-cells from alpha-1-deficient (alpha1-/-) mice. 2) Determine the importance of granulocyte (e.g. monocyte/macrophage, PMNs) alpha-1-beta-1 surface expression on the initiation and/or perpetuation of chronic gut inflammation using RAG-2-/- x alpha-1-/- doubledeficient recipient animals. Understanding the importance of this integrin in an immune-based model of IBD may provide new insights into the pathogenesis of chronic gut inflammation and provide new therapeutic approaches for the treatment of human IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF THE CO-STIMULATOR MOLECULAR SLAM IN COLITIS Principal Investigator & Institution: Faubion, William A.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Dysregulation of activated T cells leading to a chronic inflammatory state is a central feature of inflammatory boweI disease (ulcerative colitis and Crohn's disease). Co-stimulatory molecules expressed on activated T cells

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and antigen presenting cells (i.e. macrophages and dendritic ceils) orchestrate T cell((antigen presenting cell interaction and define the type of T cell response (i.e. activation vs. anergy). SLAM (signaling leukocytic activation molecule, CD150) is a costimulatory molecule highly expressed on both activated T cells and macrophages. Through augmentation of pro-inflammatory cytokines, SLAM co-stimulation potentiates the inflammatory state. Preliminary data suggest that disruption of SLAM signaling on activated T cells protects against colitis and SLAM deficient (SLAM-/-) macrophages have a profound defect in pro-inflammatory function. Based on this work we generate the novel hypothesis that SLAM co-stimulation is critical to the function of both macrophages and activated T cells that mediate chronic inflammation in colitis. In specific aim #1, we will use SLAM -/- mice crossed to the Rag-/- background (no T or B cells) to test the hypothesis that SLAM expression on antigen presenting cells is critical to the induction and maintenance of experimental colitis. In specific aim #2, the potential of SLAM-/- T cells to cause colitis will be studied. The ability of anti-SLAM antibodies to prevent colitis will be tested in vivo in two models of experimental colitis in specific aim #3. The studies will test activation states of different T cell subsets and macrophages in vitro by cytokine assay (ELISA). Assessment of colitis in vivo will be made by clinical parameters (i.e. weight loss, diarrhea) as well as histologic scoring of the colon at autopsy. This work will establish the role for SLAM in the initiation and maintenance of colitis and has the potential of identifying a new therapeutic target for the immune modulation of human inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF TNF IN BLADDER INFLAMMATION Principal Investigator & Institution: Klumpp, David J.; Urology; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Interstitial cystitis (IC) is a debilitating, neurogenic bladder disease affecting primarily women with symptoms of pelvic pain, urinary frequency, and urgency. The etiology of IC is unknown, but chronic inflammation is associated with a large subset of patients. Mast cells are thought to play a central role in the bladder inflammation associated with IC, and we have recently shown that mast cells directly induce inflammatory responses in human urothetial cells that are mediated by tumor necrosis factor alpha (TNF). Although little is known about the role of TNF in bladder inflammation, anti-TNF therapy has proven efficacious in the treatment of other chronic inflammatory diseases including Crohn's disease and rheumatoid arthritis. Therefore, our hypothesis is that TNF is a major mediator of bladder inflammation induced by mast cells. To test this hypothesis, we have developed a culture model of mast cell-urothelial cell interactions and a mouse model of neurogenic cystitis using the neurotropic psuedorabies virus (PRV) that does not infect the bladder yet induces a centrally-mediated cystitis that mimics important aspects of IC including voiding dysfunction, involvement of mast ceils, and expression of inflammatory markers. In Aim 1, we will determine the TNF signaling requirements for urothelial inflammatory responses to primary murine mast cells in culture using specific antibodies and RNA interference technologies. In Aim 2, the role of mast cells and TNF in neurogenic cystitis will be determined by infusing wild type and TNF knockout mast cells into mast celldeficient mice and then inducing cystitis with PRV. Similar experiments will also be performed with TNF receptor knockout mice. In Aim 3, the impact of chronic TNF exposure on bladder inflammation will be assessed using an existing transgenic mouse that expresses elevated systemic TNF and using mouse lines engineered to specifically

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express TNF in the urothelium. In Aim 4, the effects of anti-TNF therapy will be tested in both the neurogenic and chronic models of TNF-induced bladder inflammation using a TNF blocking antibody. Thus, this project will determine the role of TNF in bladder inflammation and examine a potential therapy for IC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAFE FOCUSED DELIVERY OF GENE THERAPEUTICS TO COLON Principal Investigator & Institution: Sano, Takeshi; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The long-term goal of this project is to develop a safe, efficient gene transfer technology that can be used for gene therapy of diseases in the colorectal system. The R21 phase of this project will focus on the development of a gene transfer technology that allows safe, efficient, and focused delivery of transgenes to the colorectal system. During this technology development phase, we will use inflammatory bowel disease (IBD), which consists of Crohn's disease and ulcerative colitis, as a first target to assess the efficacy of the gene transfer technology. We have recently developed a novel gene transfer technology, in which viral particles (adenoviral vectors and adeno-associated viral vectors) are delivered to target sites in a microbeadassociated form. These virus-microbead conjugates can infect target cells at efficiencies much greater than the same viral vectors used free in solution. A key feature of this gene transfer technology is that the infection sites by viral vectors are equal to the contact sites between target cells and virus-microbead conjugates. This allows focused delivery of transgenes to target sites with high transduction efficiencies by placing virusmicrobead conjugates at the site of interest. Since each viral particle on the microbeads either mediates infection of a cell or stays on the microbeads, no free viral particles should be present. Thus, uncontrolled transduction of other non-target tissues or organs by viral vectors can be eliminated, and immune responses to viral vectors can be minimized. These and other characteristics suggest that this technology could allow for the efficient, safe delivery of transgenes to the colorectal system. In particular, it could be very useful for the development of effective gene therapy protocols for IBD, since a potentially efficacious gene therapy strategy for IBD is to repress intense inflammation in the colon by local, high-level expression of anti-inflammatory cytokines at inflamed lesions. We will investigate the potential of this gene transfer technology for the safe, focused delivery of the gene for a potent anti-inflammatory cytokine, interleukin-10 (IL10), to inflamed lesions in the colon for the amelioration of established colitis. We hypothesize that this technology will allow for safe, efficient, and focused delivery of the IL-10 gene to inflamed lesions in the colon, resulting in the local expression and secretion of IL-10 in the inflamed lesions for the amelioration of established colitis with minimal detrimental effects on other tissues and organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFETY AND EFFICACY OF ISIS 2302 IN STEROID DEPENDENT CROHN'S DISEASE Principal Investigator & Institution: Buchman, Alan L.; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEARCHING FOR EVIDENCE OF INFECTION IN CROHN'S DISEASE Principal Investigator & Institution: Pei, Zhiheng; Medicine; New York University School of Medicine 550 1St Ave New York, NY 10016 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: (Taken from the Investigator's Abstract) Crohn's Disease is a form of inflammatory bowel disease characterized by a genetically determined, uncontrolled aberrant immune reaction to an unknown environmental trigger, causing transmural inflammation that typically contains granulomata. The long-term goal of this research is to determine whether there is a bacterial or viral infectious etiology of CD. The hypothesis to be evaluated is that the environmental trigger is an infectious agent present within the granulomata. This hypothesis has been evaluated by many investigators. A number of bacterial and viral organisms have been detected in specimens from CD patients, but the question has never satisfactorily or conclusively been answered, because it is not known whether the detected organisms contribute to the development of CD or simply are intestinal colonizers due to fecal contamination of the specimen. The investigator will use a novel combination of molecular and pathological techniques to address this question. The specific aims of this study are to identify and characterize bacteria in CD tissue and to identify and characterize viruses in CD tissue. To accomplish these goals, an approach to isolate pathological tissue free of surface contamination and a broadly based strategy to screen for all bacteria and viruses that could be etiologic agents in CD will be employed. To identify a bacterial agent, using light microscopy, granulomas will be dissected from paraffin-embedded CD tissue blocks to obtain pathological tissue free of either mucosal or serosal contamination. After deparaffinization of the granuloma, DNA will be extracted and used as a template to amplify bacterial DNA using consensus eubacterial rDNA primers. To identify a viral agent, a serosal window will be opened on fresh ileectomy/colectomy specimens resected from CD patients, and a biopsy of the muscularis will be obtained through the window. The biopsy will be divided into two parts for extraction of DNA and total RNA, respectively, and the remaining biopsy will be submitted for histological examination. The DNA recovered will be compared with that obtained from peripheral blood/normal tissue at the margin of resection by the previously described representational difference analysis to identify the presence of exogenous DNA. The RNA recovered will be used to construct a cDNA library and the library screened using sera obtained from patients with active CD to identify clones expressing foreign antigens due to the presence of viral RNA. Foreign DNA or RNA identified will be sequenced and analyzed for phylogenetic relationships with known bacteria and viruses. This strategy will unambiguously determine whether patients with CD have bacterial or viral genetic materials located within the lesions, which will be an important step toward clarifying whether infection with the organisms(s) causes the disease. Understanding of the etiology could enable eventual development of new diagnostic methods and specific prevention and treatment strategies for CD, and clarify backgrounds for genetic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOCS2 AND INTESTINAL FIBROSIS Principal Investigator & Institution: Fruchtman, Shira; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 01-DEC-2003; Project End 31-AUG-2004

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Summary: (provided by applicant): The long-term objective of this proposal is to identify intrinsic negative modulators of inflammation-induced fibrosis, an incurable complication of Crohn's disease. The key to controlling fibrosis is to define mechanisms which permit normal wound healing but prevent these healing responses from becoming excessive. Considerable evidence indicates that locally expressed insulin-like growth factor-I (IGF-I) is upregulated in myofibroblasts at sites of fibrosis in Crohn's disease and in animals models with experimentally induced intestinal inflammation. Preliminary evidence supports the hypothesis that suppressor of cytokine signaling-2 (SOCS2) limits the fibrogenic effects of IGF-I in the inflamed intestine. After acute colitis, mice deficient in both SOCS2 alleles show increased collagen deposition and augmented IGF-I expression compared to wild type (WT) mice suggesting that SOCS2 may suppress inflammation-induced fibrosis mediated by IGF-I. One aim of this study is to determine the mechanism by which SOCS2 limits IGF-I action. These studies will use cultured myofibroblasts which overexpress SOCS2 to define those signaling molecules within the IGF-I pathway that are inhibited by SOCS2. The second aim is to test the hypothesis that mice with mesenchymal cell-specific ablation of SOCS2 show more severe fibrosis than WT littermates after acute mucosal injury induced by sodium dextran sulfate (DSS) or colitis induced by trinitrobenzene sulfonic acid (TNBS). Defining how SOCS2 limits fibrosis may provide new insights into strategies or therapies that limit or prevent fibrosis in Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE STUDIES ON PROTEINS THAT MODULATE IL-10 ACTION Principal Investigator & Institution: Walter, Mark R.; Associate Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2005 Summary: (From the applicant's abstract) The overall goal of this research is to identify the structural basis for protein-protein interactions that modulate interleukin 10 (IL-10) biological activities by elucidating crystal structures of IL-10 complexed with its cell surface receptors, and several Fab fragments of neutralizing antibodies using X-ray diffraction techniques. These data will be used to design IL-10 mutants that enhance or prevent IL-10/IL-10 receptor interactions as well as mutants that change the geometry and/or the stoichiometry of the IL-10 receptor-ligand complex. Formation of a complex consisting of IL-10, a high affinity receptor (IL-10Ralpha), and a signal transducing receptor (IL-10Rbeta) is required for the generation of IL-10 biological activities that suppress TH1-dependent, cell-mediated immune responses. As a result of these activities, IL-10 is a very promising protein therapeutic for the treatment of chronic inflammatory diseases. IL-10 is currently in phase III clinical trials for Crohn's disease and phase II trials for rheumatoid arthritis that affects 40 million people and costs the country over 65 billion dollars annually in work disability. In addition to its immunosuppressive role, IL-10 has been implicated as an autocrine growth factor responsible in the pathogenesis of several B-cell malignancies. Thus, antagonists of IL-10 have potential therapeutic applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES IN CHILDREN WITH DIGESTIVE DISORDERS Principal Investigator & Institution: Heyman, Melvin B.; Professor of Pediatrics; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122

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Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: Clinical research in pediatric disorders is essential to ensure advances in the management, prognosis and quality of life of infants, children and adolescents with these problems. The goals are (1) to foster a program in hypothesis-driven, expert clinical research in pediatric gastroenterology and nutrition, (2) to mentor young clinicians in pediatric gastroenterology and nutrition research, and (3) to promote ongoing interactions and collaborations with clinical investigators. To achieve these goals, current projects and future investigations of gastrointestinal and nutrition problems in pediatric patients will be conducted by trainees at various levels under the guidance and supervision of Dr. Heyman and his collaborators. Studies involving pediatric patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis), HIV infection, familial adenomatous polyposis syndrome (with FAP gene mutations), ichthyosis erythrodermas with poor nutrition, and gastroesophageal reflux disease are currently ongoing or planned utilizing the facilities and staffs of the Pediatric Gastroenterology/Nutrition Clinics and the Pediatric Clinical Research Center at the University of California, San Francisco (UCSF). A cohort study is in the planning stage to determine whether nutrition advice promotes improved long-term outcomes in eating behaviors and health status (e.g., micronutrient adequacy; and growth parameters). The overriding objective of this proposal is to motivate and inspire young clinicians embarking on careers focused on clinically oriented research. Pediatric gastroenterology trainees will be instructed in the proper conduct of perspective randomized controlled clinical trials in infants, children, and adolescents. Trainees will also participate in didactic courses covering clinical trial design and procedure, protocol writing, data management, and ethical considerations. This award will enhance the applicant's ability to devote more time to research- related activities, and to provide guidance and instruction for trainees advancing towards productive scientific careers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED DEGRADATION OF PKR MRNA WITH 2-5A ANTISENSE Principal Investigator & Institution: Xu, Zan; Ridgeway Biosystems, Inc. 9500 Euclid Ave, Nd-50 Cleveland, OH 44195 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-AUG-2003 Summary: (provided by applicant): Inflammatory diseases represent increasing health care cost to American people. For many chronic inflammatory diseases (asthma, rheumatoid arthritis, bowel inflammatory diseases, etc.), there are no effective treatment. With the increase in the aging population of American society, this problem becomes aggravating. Targeted degradation of important factors (cytokines, cytokine receptors and intracellular mediators) participating in the inflammation signaling is a cost-effective strategy to develop an anti-inflammatory therapeutic measure. PKR is emerging as an important mediator for inflammatory process by transducing signaling activation of NF-kappa B or p38 to activate gene transcription of a number of inflammatory cytokines. Therefore, disruption of PKR activity is a particular attractive means of treating inflammatory diseases. The advantage of selecting PKR as a target also resides in that PKR is nonessential protein for cell survival compared with other targets (TNF-alpha, NF-kappa B, p38, etc.) which are vital for cell survival. Disruption of their activities may lead to undesirable and unexpected side effects. RBI is developing a novel class of chimerical oligonucleotides for use in antisense therapeutic strategies. This chimeras are comprised of an antisense component, which directs the compound to the complementary PKR sequences, and an activator moiety, 2',5'-oligoadenylate (2-5A)

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that serves to activate a cellular enzyme, ribonuclease L (RNase L), which cleaves the target RNA. Preliminary results demonstrated that 2-5A anti-PKR chimera can efficiently degrade PKR and inhibit PKR activation. The goal of this proposal is to progress this compound toward commercialization by obtaining a lead chimera compound with affinity to both human and murine PKR mRNA, and investigating the anti-inflammatory activity of the lead compound. If successful, the 2-5A anti-PKR compound will have a potential application to the treatment of chronic inflammatory diseases including rheumatoid arthritis, Crohn's diseases etc. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TH2 CELLS DIRECT THE GENESIS OF COLONIC PATCHES AND IBD Principal Investigator & Institution: Mcghee, Jerry R.; Professor; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001 Summary: Inflammatory bowel disease (IBD) are chronic, relapsing, tissue destructive disease. Recent advances in experimental models for IBD in mice have contributed to a better understand of the mechanisms of intestinal inflammation involving dysfunction of T cells and dysregulation of cytokine production. Notably, a central role for interferon-gamma (IFN-gamma) produced by T helper type 1 (Th1)-T cells and for inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been emphasized in these murine models. However, the immunological events which occur in human IBD are not always accommodated by these models. In ulcerative colitis, it is generally recognized that a role for TH1-type responses are not as evident as in Crohn's disease. In our recent investigation, we have obtained evidence that Th2-type responses are also much involved in a murine hapten-induced IBD model which is accompanied by expansion of colonic patches, which are the gut associated lymphoreticular tissues in the colon. Since inflammatory lesions were induced in a condition deficient in Th1 type cells producing IFN-gamma, and were distinct from the lesions seen in mice deficient in Th2 cytokines, we hypothesize that cytokine-phenotypes may explain the different pathological findings in ulcerative colitis and Crohn's disease. The major goal of this grant is to show that Th2-type responses can induce distinct types of lesions from those caused by Th1-type responses. Further, we will define colonic patches as inductive sites of chronic intestinal inflammation that occur through Th2 immune responses. To address this goal, the first aim will be to study the specific roles of Th2-type cells in murine intestinal inflammation through an adoptive transfer system of CD4+ CD45RB/Hi T cells. This study will be done with interactions with project 1 (Dr. Elson) in which adoptive transfer of Th1- or Th2-skewed T cells derived from C3H/HeJBir mice will also be investigated. In the second aim, we will define specific functions for colonic patches by comparing them with Peyer's patches for immune responses to defined antigens and delivery vectors/adjuvants which induced mucosal immunity via Th1- or Th2-type T cells. This study will interact with Project 2 (Dr. Weaver) for studies of antigen (OVA)-specific responses. The third aim will determine if colonic patches are necessary to induce intestinal inflammation by using mice deficient in organized colonic patches. Finally our last aim will define novel molecules which are specifically expressed in colonic patches using 2 dimensional gel analysis and differential display of mRNA between Peyer's and colonic patches. These latter techniques will also be applied to Project 4 (Dr. Leiter) to compare congenic stocks of mice which are done to develop inflammation. These proposed studies will provide new information for understanding

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the pathogenesis of non-Th1 type intestinal inflammation and the role of organized colonic patch lymphoid tissues in IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF MYCOBACTERIA IN CROHN'S DISEASE Principal Investigator & Institution: Graham, David Y.; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: (provided by applicant): Crohn's disease is an idiopathic non- caseating granulomatous disease. One of the proposed etiologies is infection with Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis), the causative agent of Crohn's-like disease in ruminants (Johne's disease). Recent evidences to support M paratuberculosis infection in Crohn's disease include: 1) its isolation from Crohn's disease tissues and breast milk by culture, 2) its identification in tissues by PCR assays, 3) its detection as cell wall deficient forms in tissues by in situ hybridization, 4) the long term remission (possibly cure) in an increasing number of Crohn's patients by using anti-mycobacterial therapies, and 5) by an association with the M paratuberculosis antigens p35, p36 and the 32k mycobacterial associated antigen termed HupB protein. These data suggest a causal role for mycobacteria in at least a proportion of patients with Crohn's disease. Identification of the subgroup of Crohn's disease patients infected with M paratuberculosis has been hampered due to the lack of a simple and specific serodiagnostic test to identify those who would be candidates for anti- mycobacterial therapy. The long-range objective of this proposal is to confirm M paratuberculosis p35/ p36 antigens as serologic markers and to test whether there are specific clinical/pathologic stratification(s) that correlate with their presence. We will assess the presence of M paratuberculosis infection in Crohn's disease patients by serologic testing of sera from patients and controls and in situ hybridization for the detection of the cell wall-deficient form of M paratuberculosis in involved diseased tissues. We will also use the laser capture microdissection technique to test whether M paratuberculosis are present in granulomas of Crohn's disease patients. The results from serology and molecular studies will be compared with the clinical/pathological information and demographic and epidemiologic data gathered about each patient as well as with outcome of anti-mycobacterial therapy. The results of this study should either confirm or refute the proposed etiologic association of M. paratuberculosis and Crohn's disease as well as the identification of patients with Crohn's disease and M. paratuberculosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TNF ALPHA AND CROHNS DISEASE MUCOSAL INFLAMMATION Principal Investigator & Institution: Targan, Stephan R.; Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: Tumor Necrosis Factor-alpha (TNF-alpha) has been implicated as a mediator of inflammatory processes in IBD. A possible mechanism by which TNF-alpha generates this enhanced mucosal inflammation was suggested by studies in animals showing downregulation of mucosal Th1 cytokine production following anti-TNF-alpha treatment. The role of TNF-alpha as a mediator of immune function and mucosal inflammation in Crohn's disease has been demonstrated by dramatic clinical responses in a series of trials in which patients received a single infusion of anti-TNF-alpha monoclonal antibody. Follow-up evaluation of these patients demonstrated prolonged

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effects of the infusion with duration of response up to one year. This extended response is evident long after anti-TNF-alpha has cleared the body and suggests that the transient block of the direct, damaging effect of TNF-alpha is accompanied by a more sustained normalization of the characteristic exaggerated immune response. This concept is supported by parallel studies of patients responding to anti-TNF- alpha, in which mucosal Th1 cytokine responses in inflamed tissue were shown to be sequentially down-regulated to levels typical of uninvolved mucosa. These results demonstrate that TNF-alpha may mediate the enhanced mucosal Th1 cell production of IFN-gamma seen in Crohn's disease mucosa. It is likely that treatment with anti-TNF-alpha inhibits TNFalphamediation of IFN-gamma production, resulting in a prolonged effect on mucosal inflammation in the majority of Crohn's patients. To begin to investigate the role of TNF-alpha in modulation of mucosal Th1 function, we have developed an in vitro system for Crohn's disease-like (Th1 phenotype) inflammation in lamina propria mononuclear cells, which we have used to demonstrate that prolonged exposure to TNF-alpha upregulates Th1 cytokine production. Preliminary data suggest that this upregulation requires the presence of non-T-cells and non-B-cells, and is IL- 12, IL-18, IL-4 and IL-10 independent. Multiple manipulations of peripheral blood cells to recreate this phenomenon have not been successful, suggesting that unique properties of the mucosal compartment may regulate the effects of TNF-alpha. To this end, co-culture of LPMC supernatants containing a heat soluble factor is capable of inducing PBMC to increase production of IFN-gamma in response to TNF-alpha. Our experimental system will further elucidate the mechanism(s) of TNF-alpha modulation of mucosal Th1 cell function. Furthermore, it will allow studies to define new targets for therapeutic approaches aimed at selectively downregulating the TNF-alpha mediated, enhancement of Th1 responses in Crohn's mucosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TNF RECEPTORS OF COLONIC EPITHELIAL CELLS IN IBD Principal Investigator & Institution: Mizoguchi, Emiko; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Tumor necrosis factor-alpha (TNFalpha) induces multiple physiological effects through distinct signaling cascades associated with TNF receptor-type I (TNFR1) and -type II (TNFR2). TNFalpha plays an important role in the pathogenesis of inflammatory bowel disease (IBD) and neutralization of TNFalpha is effective in the treatment of Crohn's disease (CD). TNFR2 can be expressed by inflammatory cells including lymphocytes and macrophages as well as colonic epithelial cells (CEC) under inflammatory conditions, and the induction of TNFR2 expression on CEC is associated with the development of IBD. TNFR1 which is constitutively expressed on the CEC seems to be involved in the regulation of TNFR2 expression. The experiments in the proposal are designed to test the hypothesis that TNFalpha/TNFRs interactions on CEC play functionally distinct roles from those on immune cells in the development of colitis. We also hypothesize that the TNFRs mediate different responses in T helper type 1 (Th1)- and T helper type 2 (Th2)-dominant chronic colitis. In Aim I, we plan to define the cooperative effect of TNFR1 and TNFR2 on the CEC proliferation in the context of experimental inflammation. In Aim II, we plan to define the role of TNFR2 on CEC and macrophages in the development of Th1-mediated colitis. In Aim III, we plan to define the role of TNFRs on CEC in the pathogenesis of Th2-mediated chronic colitis. These studies will help clarify the functional role of TNF/TNFRs interaction on CEC in the pathogenesis of IBD. This application is for a Mentored

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Clinical Scientist Development Award to an applicant who has completed training in internal medicine, and has received pre-and post-doctoral training in Immunology and immunopathology. The applicant's long term goals are to establish and direct her own independent basic research program in studies to link epithelial biology in inflammatory bowel disease. Accordingly, these studies are sponsored by Dr. Daniel K. Podolsky from the Division of Gastroenterology and by Dr. Atul K. Bhan from the Immunopathology Unit, both at Massachusetts General Hospital and Harvard Medical School. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TNF-ALPHA PERMEABILITY

MODULATION

OF

INTESTINAL

EPITH.

Principal Investigator & Institution: Ma, Thomas Y.; Professor; Internal Medicine; University of New Mexico Albuquerque Controller's Office Albuquerque, NM 87131 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Patients with Crohn's disease (CD) have a defective intestinal epithelial tight junction (TJ) barrier manifested by an increase in intestinal permeability. The defective intestinal epithelial TJ barrier appears to be an important pathogenic factor of CD, which allows intestinal penetration of toxic luminal antigens and substances leading to the intestinal inflammation. Tumor necrosis factor-alpha (TNF-alpha) plays a central causative role in intestinal inflammation of CD. Several recent studies including our preliminary studies demonstrated that TNF-alpha produces a persistent increase in intestinal epithelial TJ permeability. The TNF-alpha induced increase in intestinal epithelial TJ permeability could be an important pro-inflammatory mechanism, which allows increased intestinal permeation of toxic luminal antigens. Since TNF-alpha plays a central role in the intestinal inflammation of CD, understanding the intracellular mechanisms involved in TNF-( induced increase in intestinal TJ permeability will be crucial in developing potential therapeutic strategies to prevent the abnormal increase in intestinal TJ permeability. In this grant application, we propose to delineate the cellular and molecular mechanisms, which mediate the TNFalpha induced increase in intestinal TJ permeability, using the Caco-2 Intestinal epithelial cells. Based on our preliminary data, we hypothesize that TNF-alpha induced NF-kappaB activation is a key intracellular process, which regulates the TNF-alpha modulation of the intestinal epithelial TJ barrier. The proposed specific aims of this grant application will test the hypothesis that NF-(B activation is a key intracellular process regulating the TNF-alpha induced increase in intestinal epithelial TJ (or paracellular) permeability. The proposed specific aims will also 1) delineate the intracellular mechanisms which regulate the TNF-alpha induced NF-kappaB activation and increase in intestinal epithelial TJ permeability, 2) determine the molecular and cellular mechanisms by which TNF-alpha regulates the TJ proteins, and 3) determine the possible intracellular targets for therapeutic intervention to prevent the TNF-alpha induced increase in intestinal TJ permeability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TO EVALUATE SAFETY & EFFICACY OF ISIS 2303 IN STEROID DEPD CROHNS DISEASE Principal Investigator & Institution: Varilek, Gary W.; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2001

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Summary: This is a D protocol with IRB approval. The object is to study the safety and efficacy of ISIS 2302 in steroid-dependent Crohn's disease. ISIS 2302 is antiinflammatory, anti-sense therapy. This is based on its ability to bind to and inhibit synthesis of Intercellular Adhesion Molecule-1 (ICAM-1). ICAM-1 is a central molecule in the immune and subsequent inflammatory response involved in the movement of white blood cells from the blood to sites of inflammation. The study is aimed to evaluate whether ISIS 2302 could offer an alternative treatment to patients with Crohn's disease who are dependent on systemic steroids which have broad and serious side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSITION FROM EARLY TO LATE COLITIS--IL 12 REGULATION Principal Investigator & Institution: Levine, Alan D.; Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Inflammatory bowel disease (IBD) is a chronic and relapsing disease of unknown etiology. The regulatory and environmental events that modulate inflammation or trigger a new round of symptoms are completely uncharacterized. The majority of information about factors which perpetuate inflammation in IBD is obtained from chronically inflamed human tissue, while the data from animal models of IBD derives overwhelmingly from early immune responses. In this project we propose to bridge that gap by contrasting the regulation and expression of inflammatory mediators by mucosal immune cells during early and late enterocolitis in murine models. In a healthy individual exposure to a pathogen results in a highly regulated immune response that first clears the organism and then returns to a controlled state. It is our premise that the chronic inflammation observed in ulcerative colitis and Crohn's disease results from an inability of the mucosal immune response to return to this controlled state. Thus, we present the following central hypothesis: Inflammation in experimental murine models of IBD is initiated by mucosal T cell responses to enterobacterial antigens, and it is perpetuated during the late chronic phase by a proinflammatory response maintained by mucosal immune and non-immune cells. A corollary of this hypothesis is that the immune response generated in early IBD and toward an infectious pathogen are similar and that the characterize and immune mediator profile of early immunity is distinct from the immune response that causes chronic inflammation. In support of this premise we have demonstrated in a T celldependent animal model of enterocolitis (i.e., the IL-10 deficient (IL-10-/-) strain of mice) that the mucosal cytokine profile and anti-cytokine therapeutic efficacy are remarkably different during the early and late phases of intestinal inflammation. We will test this hypothesis with four specific aims: (1) Define the molecular events that regulate mucosal synthesis of IL-12 and IFN-gamma in the early phase of experimental colitis in IL-10-/- mice; 2) Characterize the inflammatory mediators that down-regulate IL-12 synthesis and orchestrate the transition to the late phase of gut inflammation; (3) Investigate the ability of commensal bacterial flora, in general, and Helicobacter species, in particular, to initiate and sustain inflammation in early and late disease; and (4) Identify components of the immune response that support the chronicity of inflammation in the absence of IL- 12 and IFN-gamma production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TREATMENT OF CROHN'S DISEASE WITH GROWTH HORMONE Principal Investigator & Institution: Hannon, Tamara S.; Pediatrics; Indiana UnivPurdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167

70 Crohn’s Disease

Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): It is the investigator's career goal to obtain a faculty position in an academic medical center where she expects to develop an independent research program. A Research Career Award will not only allow for the development of enhanced research skills and knowledge from implementing the clinical research project, but will allow for formal didactic training in the basic skills required to develop expertise as an academic independent clinical researcher. Through participation in the IU Clinical Investigator Training Enhancement Program, she will receive the didactic training necessary for a career in clinical research. The environment at the IU School of Medicine (IUSM) is outstanding and she has been given full support from the Director of Pediatrics and the Director of the GCRC. She expects to develop expertise in the use of state-of-the-art metabolic techniques for investigating clinical endocrine questions. The proposed project aims to assess medical outcomes of growth hormone (GH) and GH releasing hormone (GHRH) therapy in patients with Crohn's disease. To date, there are limited data on the efficacy of GH in Crohn's disease. GHRH is a peptide that stimulates the synthesis and secretion of GH from the somatotrope cells of the anterior pituitary gland and is used therapeutically in some GH deficient patients. Interestingly, GHRH is also naturally found in the gut. It is not known if GHRH has local actions in the gut. It is hypothesized that treatment with human GH will be beneficial to patients with Crohn's disease by decreasing disease severity, improving growth, enhancing protein synthesis, and increasing bone mineral density. Furthermore, she hypothesizes that GHRH will have a comparable effect on protein synthesis and bone mineral density. It will possibly have a greater effect on disease severity because of the possibility that it may have local effects in the gut. The purpose of this study is to test these hypotheses in a prospective, randomized, double-blind clinical trial. The objectives of the study are to assess medical outcomes of the treatment, to evaluate growth, to measure bone turnover and bone density, to access changes in body composition, and to evaluate whole body proteolysis and protein synthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ZINC METABOLISM IN HEALTH AND CIBD CHILDREN Principal Investigator & Institution: Abrams, Steven A.; Professor; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001 Summary: Patients with chronic inflammatory bowel disease, especially Crohn's disease, often develop decreased zinc levels. This is especially problematic in pediatric patients with Crohn's since zinc deficiency can exacerbate symptoms associated with Crohn's disease including growth stunting, impaired would healing, susceptibility to infections, and gastrointestinal derangements. Many hypotheses have been proposed in prior studies, but not clear etiology has been defined. In our study, we utilized stable isotope techniques to study zinc metabolism in children with Crohn's disease (CD) and matched healthy controls. We hypothesized that children with Crohn's would exhibit lower plasma zinc levels, decreased zinc body pool masses, increased endogenous fecal zinc excretion, and lower fractional zinc absorption than controls. In our study, enrolled subjects are admitted for a six day stay after completing a 14-day zinc adaptation diet (12 mg/d) to complete 24-hour cumulative urine and fecal specimens, as well as daily serum samples, following the administration of 0.5 mg 67Zn (po) and 70Zn (iv). Zinc absorption, endogenous fecal excretion, fractional zinc absorption, and zinc pool masses are calculated from isotope enrichments (determined via mass spectrometry) and cumulative zinc excretion from the samples. At the present time 12 Crohn's patients and

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12 controls have been studied, with the remainder of the controls (13), and Crohn's patients (3) to be studied by September 2000. Compartmental models will also be completed on all subjects. Preliminary data sets from the first five subjects with Crohn's disease when compared to the controls showed abnormal zinc metabolism in the children with Crohn's. They exhibited increased endogenous fecal zinc excretion, along with lower plasma zinc absorption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ZINC SUPPLEMENTATION IN CROHN'S DISEASE PATIENTS Principal Investigator & Institution: Disilvestro, Robert A.; Human Nutrition and Food Mgmt; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: (adapted from the application) Nutritional deficiencies seem common in Crohn's disease patients, but the benefits of correcting specific deficiencies remain largely unclear. This project tests the hypothesis that increased zinc intake, by subjects with active Crohn's disease (N=15), beneficially impacts measurements of general zinc function, Crohn's disease activity index (CDAI), immune function and free radicalmediated oxidant stress. Results will be compared to placebo effects in other Crohn's patients (N=15). Each of the project's patients will show moderate zinc deficiency based on lymphocyte zinc values. Immune function and oxidant stress will be studied because both affect overall health, and both seem to affect bowel inflammation, the primary pathology of Crohn's disease. Increased zinc intake would be accomplished by supplementation at 45 mg/day (3 times the USRDA) for 10 weeks. The supplement will be glycine-chelated zinc, which is better absorbed than zinc oxide, which appears in many multivitamin-mineral tablets. Immune function will be monitored by blood measurements meeting two criteria: abnormal values occur in Crohn's disease patients; and values are known to be affected by zinc status. Oxidant stress will be evaluated in colon biopsy samples. Any improvements in CDAI, or measurements for immune function or oxidant stress, will be compared with changes in blood or colon indicators of general zinc functional status to test for possible correlations. Positive results in this project will lead to expanded versions which examine more subjects, extend the supplementation period, combine zinc supplements with supplements of other nutrients, consider dietary food interventions which increase zinc ,intake, and examine long term assessment of pathology symptoms. 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

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.

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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Crohn’s disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Crohn’s disease in the PubMed Central database: •

A national survey on the patterns of treatment of inflammatory bowel disease in Canada. by Hilsden RJ, Verhoef MJ, Best A, Pocobelli G. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166136

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Adherent Invasive Escherichia coli Strains from Patients with Crohn's Disease Survive and Replicate within Macrophages without Inducing Host Cell Death. by Glasser AL, Boudeau J, Barnich N, Perruchot MH, Colombel JF, Darfeuille-Michaud A. 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98666

•

An Increased Risk of Crohn's Disease in Individuals Who Inherit the HLA Class II DRB3*0301 Allele. by Forcione DG, Sands B, Isselbacher KJ, Rustg A, Podolsky DK, Pillai S. 1996 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39412

•

Assessing health-related quality of life in patients with inflammatory bowel disease, in Crete, Greece. by Pallis AG, Vlachonikolis IG, Mouzas IA. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65681

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Clinical Aspects and Pathophysiology of Inflammatory Bowel Disease. by Hendrickson BA, Gokhale R, Cho JH. 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=118061

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Clinical nutrition: 6. Management of nutritional problems of patients with Crohn's disease. by Jeejeebhoy KN. 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=100927

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Colonic tuberculosis mimicking Crohn's disease: case report. by Chatzicostas C, Koutroubakis IE, Tzardi M, Roussomoustakaki M, Prassopoulos P, Kouroumalis EA. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115203

•

Does month of birth affect risk of Crohn's disease in childhood and adolescence? by Sorensen HT, Pedersen L, Norgard B, Fonager K, Rothman KJ. 2001 Oct 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58542

•

Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol. by Cioffi U, Ciulla MM, De Simone M, Paliotti R, Pierini A, Magrini F, Botti F, Contessini-Avesani E. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128828

•

Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease? by Cornet A, Savidge TC, Cabarrocas J, Deng WL, Colombel JF, Lassmann H, Desreumaux P, Liblau RS. 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60866

5

The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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•

Identification of a Novel Mycobacterial Histone H1 Homologue (HupB) as an Antigenic Target of pANCA Monoclonal Antibody and Serum Immunoglobulin A from Patients with Crohn's Disease. by Cohavy O, Harth G, Horwitz M, Eggena M, Landers C, Sutton C, Targan SR, Braun J. 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97061

•

Identification of Mycobacterium avium subsp. paratuberculosis in Biopsy Specimens from Patients with Crohn's Disease Identified by In Situ Hybridization. by Sechi LA, Manuela M, Francesco T, Amelia L, Antonello S, Giovanni F, Stefania Z. 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88575

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Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1. by Cho JH, Nicolae DL, Gold LH, Fields CT, LaBuda MC, Rohal PM, Pickles MR, Qin L, Fu Y, Mann JS, Kirschner BS, Jabs EW, Weber J, Hanauer SB, Bayless TM, Brant SR. 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22666

•

Invasive Ability of an Escherichia coli Strain Isolated from the Ileal Mucosa of a Patient with Crohn's Disease. by Boudeau J, Glasser AL, Masseret E, Joly B, DarfeuilleMichaud A. 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96770

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Is it Crohn's disease? A severe systemic granulomatous reaction to sulfasalazine in patient with rheumatoid arthritis. by Quallich LG, Greenson J, Haftel HM, Fontana RJ. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56591

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Molecular Cloning of a Bacteroides caccae TonB-Linked Outer Membrane Protein Identified by an Inflammatory Bowel Disease Marker Antibody. by Wei B, Dalwadi H, Gordon LK, Landers C, Bruckner D, Targan SR, Braun J. 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98733

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Mycobacterium avium subsp. paratuberculosis in Crohn's Disease Is Serologically Positive. by Naser S, Shafran I. 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95703

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Neglect of growth and development in the clinical monitoring of children and teenagers with inflammatory bowel disease: review of case records. by Ghosh S, Drummond HE, Ferguson A. 1998 Jul 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28604

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Positive IS900 In Situ Hybridization Signals as Evidence for Role of Mycobacterium avium subsp. paratuberculosis in Etiology of Crohn's Disease. by Roholl PJ. 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=120650

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Prevalence of inflammatory bowel disease in British 26 year olds: national longitudinal birth cohort. by Montgomery SM, Morris DL, Thompson NP, Subhani J, Pounder RE, Wakefield AJ. 1998 Apr 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28509

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Pseudomonas fluorescens Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen. by Wei B, Huang T, Dalwadi H, Sutton CL, Bruckner D, Braun J. 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=133002

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Results of Multiple Diagnostic Tests for Mycobacterium avium subsp. paratuberculosis in Patients with Inflammatory Bowel Disease and in Controls. by Collins MT, Lisby G, Moser C, Chicks D, Christensen S, Reichelderfer M, Hoiby N, Harms BA, Thomsen OO, Skibsted U, Binder V. 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87608

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Specific antibody response to oligomannosidic epitopes in Crohn's disease.. by Sendid B, Colombel JF, Jacquinot PM, Faille C, Fruit J, Cortot A, Lucidarme D, Camus D, Poulain D. 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=170283

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

A continuous spectrum of neutrophilic dermatoses in Crohn's disease. Author(s): Mendoza JL, Garcia-Paredes J, Pena AS, Cruz-Santamaria DM, Iglesias C, Diaz Rubio M. Source: Rev Esp Enferm Dig. 2003 March; 95(3): 233-6, 229-32. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760712&dopt=Abstract

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A critical assessment of items on the Pediatric Crohn's Disease Activity Index. Author(s): Loonen HJ, Griffiths AM, Merkus MP, Derkx HH. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 January; 36(1): 90-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500002&dopt=Abstract

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

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•

A map to the diagnosis of Crohn's disease. Author(s): Valentine JF. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 133-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769451&dopt=Abstract

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A rare case of Crohn's disease in head and neck surgery. Author(s): Clark MP, Benjamin E, Alusi G. Source: The Journal of Laryngology and Otology. 2003 February; 117(2): 146-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625894&dopt=Abstract

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A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn's disease. Author(s): Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Lofberg R, Modigliani R, Present DH, Rutgeerts P, Scholmerich J, Stange EF, Sutherland LR. Source: Gastroenterology. 2002 February; 122(2): 512-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832465&dopt=Abstract

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A role for intestinal mycoplasmas in the aetiology of Crohn's disease? Author(s): Roediger WE, Macfarlane GT. Source: Journal of Applied Microbiology. 2002; 92(3): 377-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872112&dopt=Abstract

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A third human carnitine/organic cation transporter (OCTN3) as a candidate for the 5q31 Crohn's disease locus (IBD5). Author(s): Lamhonwah AM, Skaug J, Scherer SW, Tein I. Source: Biochemical and Biophysical Research Communications. 2003 January 31; 301(1): 98-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535646&dopt=Abstract

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Abdominal tuberculosis mimicking Crohn's disease: a difficult diagnosis. Report of a case. Author(s): Petroianni A, Mugnaini L, Laurendi G, Giousue S, Schinina V, Bibbolino C, Bisetti A. Source: Panminerva Medica. 2002 June; 44(2): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032437&dopt=Abstract

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Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with Crohn's disease. Author(s): Yamazaki K, Takazoe M, Tanaka T, Kazumori T, Nakamura Y. Source: Journal of Human Genetics. 2002; 47(9): 469-72. Erratum In: J Hum Genet. 2003; 48(7): 397. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202985&dopt=Abstract

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Accumulation of mast cells and macrophages in focal active gastritis of patients with Crohn's disease. Author(s): Furusu H, Murase K, Nishida Y, Isomoto H, Takeshima F, Mizuta Y, Hewlett BR, Riddell RH, Kohno S. Source: Hepatogastroenterology. 2002 May-June; 49(45): 639-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063959&dopt=Abstract

•

Acquired epidermolysis bullosa and Crohn's disease. Author(s): Gluck M, Kayne A. Source: Gastrointestinal Endoscopy. 2003 April; 57(4): 563-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665771&dopt=Abstract

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Activity related increase of exhaled nitric oxide in Crohn's disease and ulcerative colitis: a manifestation of systemic involvement? Author(s): Koek GH, Verleden GM, Evenepoel P, Rutgeerts P. Source: Respiratory Medicine. 2002 July; 96(7): 530-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194639&dopt=Abstract

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Acute idiopathic pancreatitis complicating active Crohn's disease: favorable response to infliximab treatment. Author(s): Triantafillidis JK, Cheracakis P, Hereti IA, Argyros N, Karra E. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3334-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095387&dopt=Abstract

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Acute pancreatitis may precede the clinical manifestations of Crohn's disease. Author(s): Triantafillidis JK, Cheracakis P, Merikas EG, Peros G. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809859&dopt=Abstract

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Adenocarcinoma in Crohn's disease. Author(s): Sandmeier D, Bouzourene H. Source: Histopathology. 2003 April; 42(4): 404-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653953&dopt=Abstract

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Administration of infliximab in Crohn's disease does not deplete complement components C3 and C4. Author(s): Arnott ID, Shand A, Ghosh S. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095380&dopt=Abstract

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Adult height in patients with early onset of Crohn's disease. Author(s): Alemzadeh N, Rekers-Mombarg LT, Mearin ML, Wit JM, Lamers CB, van Hogezand RA. Source: Gut. 2002 July; 51(1): 26-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077087&dopt=Abstract

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Advances in medical therapy for Crohn's disease. Author(s): D'Haens G, Daperno M. Source: Current Gastroenterology Reports. 2002 December; 4(6): 506-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441041&dopt=Abstract

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Advantages of laparoscopic resection for ileocecal Crohn's disease. Author(s): Duepree HJ, Senagore AJ, Delaney CP, Brady KM, Fazio VW. Source: Diseases of the Colon and Rectum. 2002 May; 45(5): 605-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004208&dopt=Abstract

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Alteration in expression of beta 2 integrins on lamina propria lymphocytes in ulcerative colitis and Crohn's disease. Author(s): Bernstein CN, Sargent M, Rector E. Source: Clinical Immunology (Orlando, Fla.). 2002 July; 104(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139949&dopt=Abstract

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Alterations in serum anti-alpha-galactosyl antibodies in patients with Crohn's disease and ulcerative colitis. Author(s): D'Alessandro M, Mariani P, Lomanto D, Bachetoni A, Speranza V. Source: Clinical Immunology (Orlando, Fla.). 2002 April; 103(1): 63-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987986&dopt=Abstract

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Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Author(s): Seksik P, Rigottier-Gois L, Gramet G, Sutren M, Pochart P, Marteau P, Jian R, Dore J. Source: Gut. 2003 February; 52(2): 237-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524406&dopt=Abstract

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An analysis of factors influencing short-term and sustained response to infliximab treatment for Crohn's disease. Author(s): Arnott ID, McNeill G, Satsangi J. Source: Alimentary Pharmacology & Therapeutics. 2003 June 15; 17(12): 1451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823146&dopt=Abstract

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An old crone finds a new home: Crohn's disease and pars planitis. Author(s): Rosenbaum JT, Kurz D. Source: Ocular Immunology and Inflammation. 2002 September; 10(3): 157-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789592&dopt=Abstract

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An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn's disease. Author(s): Sabate JM, Villarejo J, Lemann M, Bonnet J, Allez M, Modigliani R. Source: Alimentary Pharmacology & Therapeutics. 2002 June; 16(6): 1117-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030953&dopt=Abstract

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An unusual way to diagnose a rare case of bladder carcinoma in a patient with Crohn's disease. Author(s): Uriburu JC, Baig MK, Singh JJ, Weiss EG, Nogueras JJ, Wexner SD. Source: International Journal of Colorectal Disease. 2003 March; 18(2): 172-3. Epub 2002 September 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548422&dopt=Abstract

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An update on the medical treatment of Crohn's disease. Author(s): Valentini G, Guidi L, Costanzo M, Ciarniello M, De Vitis I, Capristo E, Fedeli G. Source: Panminerva Medica. 2003 March; 45(1): 15-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682617&dopt=Abstract

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Analysis of the IBD5 locus and potential gene-gene interactions in Crohn's disease. Author(s): Negoro K, McGovern DP, Kinouchi Y, Takahashi S, Lench NJ, Shimosegawa T, Carey A, Cardon LR, Jewell DP, van Heel DA. Source: Gut. 2003 April; 52(4): 541-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631666&dopt=Abstract

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Anaphylaxis-like reaction to infliximab in a patient with Crohn's disease. Author(s): O'Connor M, Buchman A, Marshall G. Source: Digestive Diseases and Sciences. 2002 June; 47(6): 1323-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064808&dopt=Abstract

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Anomalous leukopoiesis in two patients with Crohn's disease. Author(s): Dialynas DP, Rodgers VD. Source: Journal of Clinical Gastroenterology. 2002 January; 34(1): 64-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743249&dopt=Abstract

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Anorectal functional disorders in the absence of anorectal inflammation in patients with Crohn's disease. Author(s): Mueller MH, Kreis ME, Gross ML, Becker HD, Zittel TT, Jehle EC. Source: The British Journal of Surgery. 2002 August; 89(8): 1027-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153630&dopt=Abstract

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Another new look at the small bowel: feasibility of three-dimensional magnetic resonance imaging to evaluate Crohn's disease. Author(s): McFarland EG. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 134-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769452&dopt=Abstract

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Antagonist: Crohn's disease recurrence can be prevented after ileal resection. Author(s): Rampton DS. Source: Gut. 2002 August; 51(2): 153-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117871&dopt=Abstract

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Anti-CD2O chimeric monoclonal antibody (rituximab) treatment of immunemediated thrombocytopenia associated with Crohn's disease. Author(s): Papadakis KA, Rosenbloom B, Targan SR. Source: Gastroenterology. 2003 February; 124(2): 583. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557172&dopt=Abstract

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Anti-glomerular basement membrane nephritis and bullous pemphigoid caused by distinct anti-alpha 3(IV)NC1 and anti-BP180 antibodies in a patient with Crohn's disease. Author(s): Plaisier E, Borradori L, Hellmark T, Wattiaux MJ, Flageul B, Mougenot B, Ronco P. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 September; 40(3): 649-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200819&dopt=Abstract

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Anti-inflammatory effects of enteral diet components on Crohn's disease-affected tissues in vitro. Author(s): Meister D, Bode J, Shand A, Ghosh S. Source: Dig Liver Dis. 2002 June; 34(6): 430-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132791&dopt=Abstract

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Anti-interleukin-6 therapy for Crohn's disease. Author(s): Ito H. Source: Current Pharmaceutical Design. 2003; 9(4): 295-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570822&dopt=Abstract

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Anti-TNF therapies have eliminated the need for steroids in pediatric Crohn's disease: con. Why use a drug with an unknown long-term safety profile if more established therapies will be effective? Author(s): Griffiths AM. Source: Inflammatory Bowel Diseases. 2001 November; 7(4): 342-4; Discussion 345-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720327&dopt=Abstract

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Anti-TNF therapies have eliminated the need for steroids in pediatric Crohn's disease: pro. Why use steroids if safer therapies are available? Author(s): Baldassano RN. Source: Inflammatory Bowel Diseases. 2001 November; 7(4): 338-41; Discussion 345-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720326&dopt=Abstract

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Anti-TNF therapy for Crohn's disease. Author(s): D'Haens G. Source: Current Pharmaceutical Design. 2003; 9(4): 289-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570820&dopt=Abstract

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Anti-tumor necrosis factor alpha monoclonal antibody (infliximab) for the treatment of Pyoderma gangrenosum associated with Crohn's disease. Author(s): Zaccagna A, Bertone A, Puiatti P, Picciotto F, Sprujevnik T, Santucci R, Rossini FP. Source: Eur J Dermatol. 2003 May-June; 13(3): 258-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804985&dopt=Abstract

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Anti-tumour necrosis factor therapy in Crohn's disease: where are we now? Author(s): van Deventer SJ. Source: Gut. 2002 September; 51(3): 362-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171957&dopt=Abstract

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Appendectomy is followed by increased risk of Crohn's disease. Author(s): Andersson RE, Olaison G, Tysk C, Ekbom A. Source: Gastroenterology. 2003 January; 124(1): 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512028&dopt=Abstract

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Appendiceal carcinoids in Crohn's disease. Author(s): Freeman HJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 January; 17(1): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560854&dopt=Abstract

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Assessment of Crohn's disease activity by Doppler sonography of the superior mesenteric artery, clinical evaluation and the Crohn's disease activity index: a prospective study. Author(s): Byrne MF, Farrell MA, Abass S, Fitzgerald A, Varghese JC, Thornton F, Murray FE, Lee MJ. Source: Clinical Radiology. 2001 December; 56(12): 973-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795926&dopt=Abstract

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Assessment of orocaecal transit time in different localization of Crohn's disease and its possible influence on clinical response to therapy. Author(s): Tursi A, Brandimarte G, Giorgetti G, Nasi G. Source: European Journal of Gastroenterology & Hepatology. 2003 January; 15(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544697&dopt=Abstract

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Association of Crohn's disease and ulcerative colitis with haplotypes of the MLH1 gene in Italian inflammatory bowel disease patients. Author(s): Annese V, Piepoli A, Andriulli A, Latiano A, Napolitano G, Li HH, Forabosco P, Devoto M. Source: Journal of Medical Genetics. 2002 May; 39(5): 332-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011151&dopt=Abstract

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Association of HLA-DR genotypes and IL-1ra gene polymorphism with treatment failure of budesonide and disease patterns in Crohn's disease. Author(s): Gelbmann CM, Rogler G, Gierend M, Gross V, Scholmerich J, Andus T. Source: European Journal of Gastroenterology & Hepatology. 2001 December; 13(12): 1431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742191&dopt=Abstract

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Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a cohort study. Author(s): Hampe J, Grebe J, Nikolaus S, Solberg C, Croucher PJ, Mascheretti S, Jahnsen J, Moum B, Klump B, Krawczak M, Mirza MM, Foelsch UR, Vatn M, Schreiber S. Source: Lancet. 2002 May 11; 359(9318): 1661-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020527&dopt=Abstract

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Association of Takayasu's arteritis and Crohn's disease. Results of a study on 44 Takayasu patients and review of the literature. Author(s): Reny JL, Paul JF, Lefebvre C, Champion K, Emmerich J, Bletry O, Piette JC, Fiessinger JN. Source: Annales De Medecine Interne. 2003 March; 154(2): 85-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746644&dopt=Abstract

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Asymptomatic elevation of serum lipase and amylase in conjunction with Crohn's disease and ulcerative colitis. Author(s): Bokemeyer B. Source: Zeitschrift Fur Gastroenterologie. 2002 January; 40(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803494&dopt=Abstract

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Atlantoaxial subluxation and pericarditis in a child with Crohn's disease. Author(s): Mahajan L, Klein A, Wyllie R, Kay M, Applegate K, Sabella C, Kuivila T. Source: The American Journal of Gastroenterology. 2001 November; 96(11): 3190-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721771&dopt=Abstract

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Autoimmune hemolytic anemia associated with Crohn's disease. Author(s): Hochman JA. Source: Inflammatory Bowel Diseases. 2002 March; 8(2): 98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854607&dopt=Abstract

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Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn's disease: a prospective cohort study. Author(s): Vermeire S, Noman M, Van Assche G, Baert F, Van Steen K, Esters N, Joossens S, Bossuyt X, Rutgeerts P. Source: Gastroenterology. 2003 July; 125(1): 32-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851868&dopt=Abstract

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Autologous hematopoietic stem cell transplantation for Crohn's disease. Author(s): Craig RM. Source: Autoimmunity Reviews. 2002 August; 1(4): 244-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849003&dopt=Abstract

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Axillary hidradenitis suppurativa successfully treated with infliximab in a Crohn's disease patient. Author(s): Katsanos KH, Christodoulou DK, Tsianos EV. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190206&dopt=Abstract

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Azathioprine and anti-TNF alpha therapies in Crohn's disease: a review of pharmacology, clinical efficacy and safety. Author(s): Arnott ID, Watts D, Satsangi J. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2003 January; 47(1): 1-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526855&dopt=Abstract

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Bacteria and Crohn's disease. Author(s): Shafran I, Decker JW. Source: The American Journal of Gastroenterology. 2001 November; 96(11): 3222-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721793&dopt=Abstract

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Bacterial translocation in patients with Crohn's disease undergoing surgery. Author(s): Takesue Y, Ohge H, Uemura K, Imamura Y, Murakami Y, Yokoyama T, Kakehashi M, Sueda T. Source: Diseases of the Colon and Rectum. 2002 December; 45(12): 1665-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473892&dopt=Abstract

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Baker's yeast in Crohn's disease--can it kill you? Author(s): Alic M. Source: The American Journal of Gastroenterology. 1999 June; 94(6): 1711. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364059&dopt=Abstract

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Barrier dysfunction and Crohn's disease. Author(s): Meddings J. Source: Annals of the New York Academy of Sciences. 2000; 915: 333-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11193596&dopt=Abstract

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Behaviour of Crohn's disease according to the Vienna classification. Author(s): Sachar DB. Source: Gut. 2002 October; 51(4): 614; Author Reply 614-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235097&dopt=Abstract

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Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease. Author(s): Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J. Source: Gut. 2001 December; 49(6): 777-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709511&dopt=Abstract

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Benign intracranial hypertension associated with budesonide treatment in children with Crohn's disease. Author(s): Levine A, Watemberg N, Hager H, Bujanover Y, Ballin A, Lerman-Sagie T. Source: Journal of Child Neurology. 2001 June; 16(6): 458-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417618&dopt=Abstract

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Biclonal lymphoplasmacytic immunocytoma associated with Crohn's disease. Author(s): Hara T, Ozaki S, Kosaka M, Fujiwara S, Wakahara Y, Endo H, Wakatsuki S, Matsumoto T. Source: Intern Med. 1999 June; 38(6): 500-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10411357&dopt=Abstract

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Bilateral phakic cystoid macular edema associated with Crohn's disease. Author(s): Mason JO 3rd. Source: Southern Medical Journal. 2002 September; 95(9): 1079-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356117&dopt=Abstract

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Bioactive IL-18 expression is up-regulated in Crohn's disease. Author(s): Monteleone G, Trapasso F, Parrello T, Biancone L, Stella A, Iuliano R, Luzza F, Fusco A, Pallone F. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 July 1; 163(1): 143-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10384110&dopt=Abstract

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Bioavailability of oral vs. subcutaneous low-dose methotrexate in patients with Crohn's disease. Author(s): Kurnik D, Loebstein R, Fishbein E, Almog S, Halkin H, Bar-Meir S, Chowers Y. Source: Alimentary Pharmacology & Therapeutics. 2003 July 1; 18(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848626&dopt=Abstract

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Biologics in peri-operative management of Crohn's disease. Author(s): Hanauer SB. Source: Acta Gastroenterol Belg. 2001 April-June; 64(2): 191-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475133&dopt=Abstract

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Biology of inflammation in Crohn's disease: mechanisms of action of anti-TNF-a therapy. Author(s): Targan SR. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 September; 14 Suppl C: 13C-16C. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023555&dopt=Abstract

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Bleeding diathesis in amyloidosis with renal insufficiency associated with Crohn's disease: response to desmopressin. Author(s): Dave SP, Greenstein AJ, Sachar DB, Harpaz N, Aledort L. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 187-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808946&dopt=Abstract

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Body composition and metabolic features in Crohn's disease: an update. Author(s): Capristo E. Source: Eur Rev Med Pharmacol Sci. 1998 May-August; 2(3-4): 111-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10546405&dopt=Abstract

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Boerhaave-mimicking esophageal perforation with subsequent esophagobronchial fistula formation as the primary manifestation of Crohn's disease. Author(s): Yekebas E, Busch C, Soehendra N, Winzer O, Rogiers X, Izbicki JR. Source: Digestive Surgery. 2000; 17(6): 631-633. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155011&dopt=Abstract

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Bone marrow transplantation in Crohn's disease. Author(s): Stricker T, Braegger CP. Source: Journal of Pediatric Gastroenterology and Nutrition. 1999 July; 29(1): 104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10400116&dopt=Abstract

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Bone marrow transplants in Crohn's disease. Author(s): Mann S. Source: Hosp Med. 1999 February; 60(2): 146. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10320851&dopt=Abstract

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Bone mineral density in children and young adults with Crohn's disease. Author(s): Semeao EJ, Jawad AF, Zemel BS, Neiswender KM, Piccoli DA, Stallings VA. Source: Inflammatory Bowel Diseases. 1999 August; 5(3): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453371&dopt=Abstract

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Bone mineral density in Crohn's disease: a longitudinal study of budesonide, prednisone, and nonsteroid therapy. Author(s): Cino M, Greenberg GR. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 915-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003427&dopt=Abstract

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Bones and Crohn's: should we treat Crohn's disease patients with alendronate? Author(s): Bailen LS. Source: Inflammatory Bowel Diseases. 2001 May; 7(2): 175-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383592&dopt=Abstract

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Bowel ultrasound in assessment of Crohn's disease and detection of related small bowel strictures: a prospective comparative study versus x ray and intraoperative findings. Author(s): Parente F, Maconi G, Bollani S, Anderloni A, Sampietro G, Cristaldi M, Franceschelli N, Bianco R, Taschieri AM, Bianchi Porro G. Source: Gut. 2002 April; 50(4): 490-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889068&dopt=Abstract

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Bowel wall thickening in patients with Crohn's disease: CT patterns and correlation with inflammatory activity. Author(s): Choi D, Jin Lee S, Ah Cho Y, Lim HK, Hoon Kim S, Jae Lee W, Hoon Lim J, Park H, Rae Lee Y. Source: Clinical Radiology. 2003 January; 58(1): 68-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565208&dopt=Abstract

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Bowel wall thickness measured by ultrasound as a marker of Crohn's disease activity in children. Author(s): Haber HP, Busch A, Ziebach R, Stern M. Source: Lancet. 2000 April 8; 355(9211): 1239-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770308&dopt=Abstract

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Brachiocephalic vein thrombosis associated with Crohn's disease. Author(s): Ribeiro JM, Rebocho L, Lucas MB, Campos P, Victorino RM. Source: Journal of Gastroenterology. 2003; 38(3): 268-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673450&dopt=Abstract

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Breath alkanes determination in ulcerative colitis and Crohn's disease. Author(s): Pelli MA, Trovarelli G, Capodicasa E, De Medio GE, Bassotti G. Source: Diseases of the Colon and Rectum. 1999 January; 42(1): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211523&dopt=Abstract

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Bronchial eosinophilic infiltration in Crohn's disease in the absence of pulmonary disease. Author(s): Louis E, Louis R, Shute J, Lau L, Franchimont D, Lamproye A, Radermecker M, Djukanovic R, Belaiche J. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1999 May; 29(5): 660-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10231326&dopt=Abstract

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Bronchial hyperresponsiveness in children and adolescents with Crohn's disease. Author(s): Mansi A, Cucchiara S, Greco L, Sarnelli P, Pisanti C, Franco MT, Santamaria F. Source: American Journal of Respiratory and Critical Care Medicine. 2000 March; 161(3 Pt 1): 1051-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712362&dopt=Abstract

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Budesonide (Entocort EC Capsules): a review of its therapeutic use in the management of active Crohn's disease in adults. Author(s): McKeage K, Goa KL. Source: Drugs. 2002; 62(15): 2263-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381231&dopt=Abstract

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Budesonide and mesalazine in active Crohn's disease: a comparison of the effects on quality of life. Author(s): Thomsen OO, Cortot A, Jewell D, Wright JP, Winter T, Veloso FT, Vatn M, Persson T, Pettersson E; International Budesonide-Mesalazine Study Group. Source: The American Journal of Gastroenterology. 2002 March; 97(3): 649-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922560&dopt=Abstract

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Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States. Author(s): Tremaine WJ, Hanauer SB, Katz S, Winston BD, Levine JG, Persson T, Persson A; Budesonide CIR United States Study Group. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1748-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135030&dopt=Abstract

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Budesonide for maintenance of remission in Crohn's disease. Author(s): Simms L, Steinhart AH. Source: Cochrane Database Syst Rev. 2001; (1): Cd002913. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279777&dopt=Abstract

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Budesonide in the treatment of Crohn's disease: a meta-analysis. Author(s): Papi C, Luchetti R, Gili L, Montanti S, Koch M, Capurso L. Source: Alimentary Pharmacology & Therapeutics. 2000 November; 14(11): 1419-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069312&dopt=Abstract

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Budesonide led to a greater remission rate and fewer severe adverse events than did mesalamine in Crohn's disease. Author(s): Rutgeerts P. Source: Gut. 1999 July; 45(1): 13-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10498451&dopt=Abstract

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Budesonide: its role in Crohn's disease therapy. Author(s): Coleman CI, Reddy P, White CM. Source: Conn Med. 2002 September; 66(9): 523-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369546&dopt=Abstract

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Bullous pemphigoid complicating Crohn's disease in a child. Author(s): Nowicki MJ, Bishop PR, Parker PH. Source: Clinical Pediatrics. 2002 January-February; 41(1): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866370&dopt=Abstract

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Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Author(s): Segain JP, Raingeard de la Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, Ferrier L, Bonnet C, Blottiere HM, Galmiche JP. Source: Gut. 2000 September; 47(3): 397-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10940278&dopt=Abstract

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Caecal amoeboma simulating malignant neoplasia, ileocaecal tuberculosis and Crohn's disease. Author(s): Majeed SK, Ghazanfar A, Ashraf J. Source: J Coll Physicians Surg Pak. 2003 February; 13(2): 116-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685960&dopt=Abstract

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Cancer of appendix as a presenting feature of Crohn's disease. Author(s): Sonwalkar SA, Denyer ME, Verbeke CS, Guillou PJ. Source: European Journal of Gastroenterology & Hepatology. 2002 September; 14(9): 1029-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352226&dopt=Abstract

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Card15 and Crohn's disease: healthy homozygous carriers of the 3020insC frameshift mutation. Author(s): Linde K, Boor PP, Houwing-Duistermaat JJ, Kuipers EJ, Wilson JH, de Rooij FW. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 613-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650796&dopt=Abstract

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Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon. Author(s): Berrebi D, Maudinas R, Hugot JP, Chamaillard M, Chareyre F, De Lagausie P, Yang C, Desreumaux P, Giovannini M, Cezard JP, Zouali H, Emilie D, Peuchmaur M. Source: Gut. 2003 June; 52(6): 840-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740340&dopt=Abstract

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CARD15/NOD2 gene variants are associated with familially occurring and complicated forms of Crohn's disease. Author(s): Helio T, Halme L, Lappalainen M, Fodstad H, Paavola-Sakki P, Turunen U, Farkkila M, Krusius T, Kontula K. Source: Gut. 2003 April; 52(4): 558-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631669&dopt=Abstract

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CARD15/NOD2 risk alleles in the development of Crohn's disease in the Australian population. Author(s): Cavanaugh JA, Adams KE, Quak EJ, Bryce ME, O'Callaghan NJ, Rodgers HJ, Magarry GR, Butler WJ, Eaden JA, Roberts-Thomson IC, Pavli P, Wilson SR, Callen DF. Source: Annals of Human Genetics. 2003 January; 67(Pt 1): 35-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556233&dopt=Abstract

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Case 3: vulval crohn's disease (VCD). Author(s): Nicolaou N, Varma S, Blackford S, Blackwell A. Source: Clinical and Experimental Dermatology. 2002 September; 27(6): 535-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372109&dopt=Abstract

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Case report: "Popcorn" dystrophic ileal calcification in a patient with Crohn's disease. Author(s): Prajapati DN, Kim JP, Spinelli KS, Sudakoff G, Stewart ET, Komorowski RA, Telford GL, Binion DG. Source: Inflammatory Bowel Diseases. 2003 January; 9(1): 25-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656134&dopt=Abstract

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Case report: magnetic resonance imaging in the diagnosis of epidural abscess complicating perirectal fistulizing Crohn's disease. Author(s): Heidemann J, Spinelli KS, Otterson MF, Binion DG. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 122-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769446&dopt=Abstract

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CCR4 is an up-regulated chemokine receptor of peripheral blood memory CD4+ T cells in Crohn's disease. Author(s): Jo Y, Matsumoto T, Yada S, Fujisawa K, Esaki M, Onai N, Matsushima K, Iida M. Source: Clinical and Experimental Immunology. 2003 May; 132(2): 332-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699425&dopt=Abstract

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CD44v6 expression in granuloma of Crohn's disease. Author(s): Ikehata A, Tomichi N. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3325-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095379&dopt=Abstract

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Characterization and clinical behavior of Crohn's disease initially presenting predominantly as colitis. Author(s): Morpurgo E, Petras R, Kimberling J, Ziegler C, Galandiuk S. Source: Diseases of the Colon and Rectum. 2003 July; 46(7): 918-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847366&dopt=Abstract

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Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn's disease. Author(s): Banks C, Bateman A, Payne R, Johnson P, Sheron N. Source: The Journal of Pathology. 2003 January; 199(1): 28-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474223&dopt=Abstract

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Clinical and demographic characterization of Jewish Crohn's disease patients in Israel. Author(s): Fidder HH, Avidan B, Lahav M, Bar-Meir S, Chowers Y. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 8-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488699&dopt=Abstract

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Clinical experience with infliximab for Crohn's disease: the first 100 patients in Edmonton, Alberta. Author(s): Sample C, Bailey RJ, Todoruk D, Sadowski D, Gramlich L, Milan M, Cherry R, Ma M, Lalor E, McKaigney J, Sherbaniuk R, Matic K, Switzer C, Fedorak RN. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 March; 16(3): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930194&dopt=Abstract

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Clinical outcome of Crohn's disease treated with infliximab. Author(s): Arslan S, Kav T, Besisik F, Kaymakoglu S, Pinarbasi B, Tozun N, Hamzaoglu HO, Duman D, Ulker A, Parlak E, Palabiyikoglu M, Dokmeci A. Source: Hepatogastroenterology. 2003 July-August; 50(52): 952-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845957&dopt=Abstract

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Clustering of Crohn's disease within affected sibships. Author(s): Hugot JP, Cezard JP, Colombel JF, Belaiche J, Almer S, Tysk C, Montague S, Gassull M, Christensen S, Finkel Y, Gower-Rousseau C, Modigliani R, Zouali H, Lesage S, Chamaillard M, Macry J, Thomas G, Victor JM; GETAID. Source: European Journal of Human Genetics : Ejhg. 2003 February; 11(2): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634866&dopt=Abstract

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Colonic inflammatory bowel disease. Medical therapies for colonic Crohn's disease and ulcerative colitis. Author(s): Tung JK, Warner AS. Source: Postgraduate Medicine. 2002 November; 112(5): 45-8, 51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462184&dopt=Abstract

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Colonic intussusception in Crohn's disease. Author(s): Draganic B, Williamson M, Stewart P. Source: The Australian and New Zealand Journal of Surgery. 1999 September; 69(9): 6834. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515350&dopt=Abstract

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Colonoscopy accurately predicts the anatomical severity of colonic Crohn's disease attacks: correlation with findings from colectomy specimens. Author(s): Nahon S, Bouhnik Y, Lavergne-Slove A, Bitoun A, Panis Y, Valleur P, Vahedi K, Messing B, Matuchansky C, Rambaud JC. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492196&dopt=Abstract

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Combined diagnostic imaging of Crohn's disease: an outlook. Author(s): Vecchioli A, Brizi MG, Masselli G, Minordi LM, Parrella A, Celi G, Mirk P, Marano P. Source: Rays. 2002 January-March; 27(1): 11-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696271&dopt=Abstract

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Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis. On behalf of the GISC. Author(s): Forabosco P, Collins A, Latiano A, Annese V, Clementi M, Andriulli A, Fortina P, Devoto M, Morton NE. Source: European Journal of Human Genetics : Ejhg. 2000 November; 8(11): 846-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11093274&dopt=Abstract

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Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn's disease: a single center experience. Author(s): Topstad DR, Panaccione R, Heine JA, Johnson DR, MacLean AR, Buie WD. Source: Diseases of the Colon and Rectum. 2003 May; 46(5): 577-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792431&dopt=Abstract

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Combined use of preoperative provocative angiography and highly selective methylene blue injection to localize an occult small-bowel bleeding site in a patient with Crohn's disease: report of a case. Author(s): Remzi FH, Dietz DW, Unal E, Levitin A, Sands MJ, Fazio VW. Source: Diseases of the Colon and Rectum. 2003 February; 46(2): 260-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576900&dopt=Abstract

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Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in Crohn's disease. Author(s): Ochsenkuhn T, Goke B, Sackmann M. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2022-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190171&dopt=Abstract

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Combining T cells and IL-10: a new therapy for Crohn's disease? Author(s): Madsen K. Source: Gastroenterology. 2002 December; 123(6): 2140-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454869&dopt=Abstract

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Comparison of conventional and laparoscopic ileocolic resection for Crohn's disease. Author(s): Bergamaschi R, Pessaux P, Arnaud JP. Source: Diseases of the Colon and Rectum. 2003 August; 46(8): 1129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907912&dopt=Abstract

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Computed tomography enteroclysis in comparison with ileoscopy in patients with Crohn's disease. Author(s): Hassan C, Cerro P, Zullo A, Spina C, Morini S. Source: International Journal of Colorectal Disease. 2003 March; 18(2): 121-5. Epub 2002 November 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548413&dopt=Abstract

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Connections between psoriasis and Crohn's disease. Author(s): Najarian DJ, Gottlieb AB. Source: Journal of the American Academy of Dermatology. 2003 June; 48(6): 805-21; Quiz 822-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789169&dopt=Abstract

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Considerations in the management of steroid-dependent Crohn's disease. Author(s): Laine L, Hanauer SB. Source: Gastroenterology. 2003 September; 125(3): 906-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949734&dopt=Abstract

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Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease. Author(s): Lovato P, Brender C, Agnholt J, Kelsen J, Kaltoft K, Svejgaard A, Eriksen KW, Woetmann A, Odum N. Source: The Journal of Biological Chemistry. 2003 May 9; 278(19): 16777-81. Epub 2003 March 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615922&dopt=Abstract

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Continuing low incidence of Crohn's disease in Northwest Greece. Author(s): Tsianos EV, Katsanos KH, Christodoulou D, Dimoliatis I, Kogevinas A, Logan RF; Northwest Greece Inflammatory Bowel Disease Study Group. Source: Dig Liver Dis. 2003 February; 35(2): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747628&dopt=Abstract

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Contrast radiology, computed tomography and ultrasonography in detecting internal fistulas and intra-abdominal abscesses in Crohn's disease: a prospective comparative study. Author(s): Maconi G, Sampietro GM, Parente F, Pompili G, Russo A, Cristaldi M, Arborio G, Ardizzone S, Matacena G, Taschieri AM, Bianchi Porro G. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1545-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873576&dopt=Abstract

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Contrast-enhanced power Doppler ultrasound in the diagnosis and follow-up of inflammatory abdominal masses in Crohn's disease. Author(s): Esteban JM, Aleixandre A, Hurtado MJ, Maldonado L, Mora FJ, Nogues E. Source: European Journal of Gastroenterology & Hepatology. 2003 March; 15(3): 253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610320&dopt=Abstract

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Corticosteroid-induced osteoporosis: does it occur in patients with Crohn's disease? Author(s): de Jong DJ, Corstens FH, Mannaerts L, van Rossum LG, Naber AH. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2011-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190169&dopt=Abstract

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Cost-effectiveness of magnetic resonance imaging and enteroclysis in the diagnostic imaging of Crohn's disease. Author(s): Ebinger M, Rieber A, Leidl R. Source: International Journal of Technology Assessment in Health Care. 2002 Summer; 18(3): 711-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391961&dopt=Abstract

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Crohn's disease and IL-10 therapy: promise regained. Author(s): de Villiers WJ. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797349&dopt=Abstract

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Crohn's disease and risk of fracture: does thyroid disease play a role? Author(s): Pooran N, Singh P, Bank S. Source: World Journal of Gastroenterology : Wjg. 2003 March; 9(3): 615-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632531&dopt=Abstract

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Crohn's disease and the NOD2 gene: a role for paneth cells. Author(s): Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S. Source: Gastroenterology. 2003 July; 125(1): 47-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851870&dopt=Abstract

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Crohn's disease complicated by relapsed extranodal Hodgkin's lymphoma: prolonged complete remission after unmanipulated PBPC autotransplant. Author(s): Musso M, Porretto F, Crescimanno A, Bondi F, Polizzi V, Scalone R. Source: Bone Marrow Transplantation. 2000 October; 26(8): 921-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081397&dopt=Abstract

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Crohn's disease in a child with Down syndrome. Author(s): Yamamoto M, Abo W, Hori T, Nakada T, Tachibana N, Hatada Y, Kaimori M. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 October; 44(5): 537-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225558&dopt=Abstract

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Crohn's disease mimicking sarcoidosis in bronchoalveolar lavage. Author(s): Bewig B, Manske I, Bottcher H, Bastian A, Nitsche R, Folsch UR. Source: Respiration; International Review of Thoracic Diseases. 1999; 66(5): 467-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516546&dopt=Abstract

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Crohn's disease of the esophagus visualized by Tc-99m antigranulocyte antibodies. Author(s): Huic D, Dodig D, Premuzic M, Krznaric Z, Vucelic B. Source: Clinical Nuclear Medicine. 2002 November; 27(11): 810-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394135&dopt=Abstract

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Crohn's disease or Crohn's diseases? Author(s): Arnott ID, Satsangi J. Source: Gut. 2003 April; 52(4): 460-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631650&dopt=Abstract

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Crohn's disease plus Takayasu's arteritis: more than coincidence? Author(s): Maksimowicz-McKinnon K, Hoffman GS. Source: Annales De Medecine Interne. 2003 March; 154(2): 75-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746642&dopt=Abstract

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Crohn's disease presenting as prepuce and scrotal edema. Author(s): Macaya A, Marcoval J, Bordas X, Moreno A, Vazquez S, Peyri J. Source: Journal of the American Academy of Dermatology. 2003 August; 49(2 Suppl Case Reports): S182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894117&dopt=Abstract

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Crohn's disease with Parkinsonism due to long-term total parenteral nutrition. Author(s): Kamata N, Oshitani N, Oiso R, Kawachiya T, Inagawa M, Kawashima D, Iimuro M, Sogawa M, Jinno Y, Watanabe K, Nakamura S, Higuchi K, Matsumoto T, Arakawa T. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 992-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772801&dopt=Abstract

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Crohn's disease: a rare cause of upper airway obstruction. Author(s): Ulrich R, Goldberg R, Line WS. Source: The Journal of Emergency Medicine. 2000 November; 19(4): 331-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074325&dopt=Abstract

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Crohn's disease: an immunodeficiency? Author(s): Folwaczny C, Glas J, Torok HP. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 621-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840672&dopt=Abstract

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Crohn's disease: aphthoid to longitudinal ulcers. Author(s): Hokama A, Kinjo F, Matayoshi R, Yonamine Y, Tomiyama R, Sunagawa T, Miyagi T, Saito A. Source: Gastrointestinal Endoscopy. 2003 March; 57(3): 388-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612527&dopt=Abstract

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Crohn's disease: ethnic variation in CARD15 genotypes. Author(s): Marsh S, McLeod HL. Source: Gut. 2003 May; 52(5): 770. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692072&dopt=Abstract

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Crohn's disease: step up or top down therapy. Author(s): Hanauer SB. Source: Best Practice & Research. Clinical Gastroenterology. 2003 February; 17(1): 131-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617888&dopt=Abstract

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Crohn's disease-associated NOD2 variants share a signaling defect in response to lipopolysaccharide and peptidoglycan. Author(s): Bonen DK, Ogura Y, Nicolae DL, Inohara N, Saab L, Tanabe T, Chen FF, Foster SJ, Duerr RH, Brant SR, Cho JH, Nunez G. Source: Gastroenterology. 2003 January; 124(1): 140-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512038&dopt=Abstract

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CT of prominent pericolic or perienteric vasculature in patients with Crohn's disease: correlation with clinical disease activity and findings on barium studies. Author(s): Lee SS, Ha HK, Yang SK, Kim AY, Kim TK, Kim PN, Lee MG, Myung SJ, Jung HY, Kim JH, Min YI. Source: Ajr. American Journal of Roentgenology. 2002 October; 179(4): 1029-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239060&dopt=Abstract

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Current issues in Crohn's disease. Author(s): Selby WS. Source: The Medical Journal of Australia. 2003 June 2; 178(11): 532-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765496&dopt=Abstract

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Current methods of bowel-sparing surgery in Crohn's disease. Author(s): Fichera A, Hurst RD, Michelassi F. Source: Adv Surg. 2003; 37: 231-51. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953636&dopt=Abstract

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Cyclooxygenase-2 expression and role of vasoconstrictor prostanoids in small mesenteric arteries from patients with Crohn's disease. Author(s): Tabernero A, Reimund JM, Chasserot S, Muller CD, Andriantsitohaina R. Source: Circulation. 2003 March 18; 107(10): 1407-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642362&dopt=Abstract

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Cytokine/chemokine messenger-RNA expression profiles in ulcerative colitis and Crohn's disease. Author(s): Autschbach F, Giese T, Gassler N, Sido B, Heuschen G, Heuschen U, Zuna I, Schulz P, Weckauf H, Berger I, Otto HF, Meuer SC. Source: Virchows Archiv : an International Journal of Pathology. 2002 November; 441(5): 500-13. Epub 2002 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447682&dopt=Abstract

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Decrease of serum carotenoids in Crohn's disease. Author(s): Rumi G Jr, Szabo I, Vincze A, Matus Z, Toth G, Mozsik G. Source: Journal of Physiology, Paris. 2000 March-April; 94(2): 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10791699&dopt=Abstract

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Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease. Author(s): Oshitani N, Hato F, Matsumoto T, Jinno Y, Sawa Y, Hara J, Nakamura S, Seki S, Arakawa T, Kitano A, Kitagawa S, Kuroki T. Source: Journal of Gastroenterology and Hepatology. 2000 December; 15(12): 1400-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197050&dopt=Abstract

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Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease. Author(s): Itoh J, de La Motte C, Strong SA, Levine AD, Fiocchi C. Source: Gut. 2001 July; 49(1): 35-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413108&dopt=Abstract

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Decreased corticosensitivity in quiescent Crohn's disease: an ex vivo study using whole blood cell cultures. Author(s): Franchimont D, Louis E, Dupont P, Vrindts-Gevaert Y, Dewe W, Chrousos G, Geenen V, Belaiche J. Source: Digestive Diseases and Sciences. 1999 June; 44(6): 1208-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389698&dopt=Abstract

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Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease. Author(s): Scheinin T, Bohling T, Halme L, Kontiainen S, Bjorge L, Meri S. Source: Human Pathology. 1999 December; 30(12): 1427-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667419&dopt=Abstract

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Decreased lamina propria effector cell responsiveness to interleukin-10 in ileal Crohn's disease. Author(s): Colpaert S, Vanstraelen K, Liu Z, Penninckx F, Geboes K, Rutgeerts P, Ceuppens J. Source: Clinical Immunology (Orlando, Fla.). 2002 January; 102(1): 68-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781069&dopt=Abstract

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Defective post-transcriptional processing of MUC2 mucin in ulcerative colitis and in Crohn's disease increases detectability of the MUC2 protein core. Author(s): Hanski C, Born M, Foss HD, Marowski B, Mansmann U, Arasteh K, Bachler B, Papenfuss M, Niedobitek F. Source: The Journal of Pathology. 1999 July; 188(3): 304-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10419600&dopt=Abstract

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Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease. Author(s): Porcher C, Baldo M, Henry M, Orsoni P, Jule Y, Ward SM. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 118-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808934&dopt=Abstract

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Defining subtypes of Crohn's disease patients: the ground work for translational research in inflammatory bowel disease. Author(s): Abreu MT, Yang H. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 3-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488696&dopt=Abstract

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Delayed and prolonged cholestatic hepatitis with ductopenia after long-term ciprofloxacin therapy for Crohn's disease. Author(s): Bataille L, Rahier J, Geubel A. Source: Journal of Hepatology. 2002 November; 37(5): 696-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399240&dopt=Abstract

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Delayed orocecal transit time and bacterial overgrowth in Crohn's disease. Author(s): Tursi A. Source: Journal of Clinical Gastroenterology. 2001 March; 32(3): 274-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246364&dopt=Abstract

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Delayed presentation of a post-episiotomy rectovaginal fistula in a patient with Crohn's disease. Author(s): Moselhi M, Rees A. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 July; 22(4): 445. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521480&dopt=Abstract

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Demographic and clinical parameters influencing the short-term outcome of antitumor necrosis factor (infliximab) treatment in Crohn's disease. Author(s): Vermeire S, Louis E, Carbonez A, Van Assche G, Noman M, Belaiche J, De Vos M, Van Gossum A, Pescatore P, Fiasse R, Pelckmans P, Reynaert H, D'Haens G, Rutgeerts P; Belgian Group of Infliximab Expanded Access Program in Crohn's Disease. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2357-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358256&dopt=Abstract

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Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn's disease. Author(s): Bull TJ, McMinn EJ, Sidi-Boumedine K, Skull A, Durkin D, Neild P, Rhodes G, Pickup R, Hermon-Taylor J. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 2915-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843021&dopt=Abstract

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Detection of anti-Saccharomyces cerevisiae antibodies in Crohn's disease: is it a reliable diagnostic and prognostic marker? Author(s): Sostegni R, Daperno M, Ercole E, Rigazio C, Bresso F, Masoero G, Castellino F, Zaffino C, Rocca R, Molinaro GC, Rocca G, Astegiano M, Pera A. Source: Dig Liver Dis. 2001 December; 33(9): 755-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838610&dopt=Abstract

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Detection of interferon regulatory factor-1 in lamina propria mononuclear cells in Crohn's disease. Author(s): Clavell M, Correa-Gracian H, Liu Z, Craver R, Brown R, SchmidtSommerfeld E, Udall J Jr, Delgado A, Mannick E. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 January; 30(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10630438&dopt=Abstract

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Detection of persistent measles virus infection in Crohn's disease: current status of experimental work. Author(s): Ghosh S, Armitage E, Wilson D, Minor PD, Afzal MA. Source: Gut. 2001 June; 48(6): 748-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358885&dopt=Abstract

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Determination of thiopurine methyltransferase genotype or phenotype optimizes initial dosing of azathioprine for the treatment of Crohn's disease. Author(s): Regueiro M, Mardini H. Source: Journal of Clinical Gastroenterology. 2002 September; 35(3): 240-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192200&dopt=Abstract

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Development and validation of an ultrasonographic activity index of Crohn's disease. Author(s): Jakab Z, Cserepes E, Tulassay Z. Source: European Journal of Gastroenterology & Hepatology. 2000 December; 12(12): 1355-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192329&dopt=Abstract

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Development and validation of an ultrasonographic activity index of Crohn's disease. Author(s): Futagami Y, Haruma K, Hata J, Fujimura J, Tani H, Okamoto E, Kajiyama G. Source: European Journal of Gastroenterology & Hepatology. 1999 September; 11(9): 1007-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10503838&dopt=Abstract

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Development of an assay for antibodies to Saccharomyces cerevisiae: Easy, cheap and specific for Crohn's disease. Author(s): Bernstein CN, Orr K, Blanchard JF, Sargent M, Workman D. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 August; 15(8): 499-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11544532&dopt=Abstract

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Development of antinuclear antibodies and its clinical impact in patients with Crohn's disease treated with chimeric monoclonal anti-TNFalpha antibodies (infliximab). Author(s): Garcia-Planella E, Domenech E, Esteve-Comas M, Bernal I, Cabre E, Boix J, Gassull MA. Source: European Journal of Gastroenterology & Hepatology. 2003 April; 15(4): 351-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655253&dopt=Abstract

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Development of rheumatoid arthritis is not associated with two polymorphisms in the Crohn's disease gene CARD15. Author(s): Steer S, Fisher SA, Fife M, Cuthbert A, Newton J, Wordsworth P, Lewis CM, Mathew CG, Lanchbury JS. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 304-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595627&dopt=Abstract

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Diagnosing small bowel Crohn's disease with wireless capsule endoscopy. Author(s): Fireman Z, Mahajna E, Broide E, Shapiro M, Fich L, Sternberg A, Kopelman Y, Scapa E. Source: Gut. 2003 March; 52(3): 390-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584221&dopt=Abstract

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Diagnosis and management of enterovesical fistulas in patients with Crohn's disease. Author(s): Gruner JS, Sehon JK, Johnson LW. Source: The American Surgeon. 2002 August; 68(8): 714-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206607&dopt=Abstract

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Diagnosis and treatment of urinary tract complications in Crohn's disease: an experience over 15 years. Author(s): Ben-Ami H, Ginesin Y, Behar DM, Fischer D, Edoute Y, Lavy A. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 April; 16(4): 225-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981574&dopt=Abstract

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Diagnosis of Crohn's disease: a wolf in sheep's clothing. Author(s): Su C, Lichtenstein GR. Source: The American Journal of Gastroenterology. 2000 December; 95(12): 3345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151860&dopt=Abstract

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Diagnostic imaging in Crohn's disease: comparison of magnetic resonance imaging and conventional imaging methods. Author(s): Rieber A, Wruk D, Potthast S, Nussle K, Reinshagen M, Adler G, Brambs HJ. Source: International Journal of Colorectal Disease. 2000 June; 15(3): 176-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10954191&dopt=Abstract

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Did President Eisenhower have Crohn's disease? Author(s): Marston A. Source: J Med Biogr. 2002 November; 10(4): 237-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389052&dopt=Abstract

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Diet and Crohn's disease. Author(s): Allen S. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1999 October 13-19; 14(4): 65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10855180&dopt=Abstract

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Dietary fat attenuates the benefits of an elemental diet in active Crohn's disease: a randomized, controlled trial. Author(s): Bamba T, Shimoyama T, Sasaki M, Tsujikawa T, Fukuda Y, Koganei K, Hibi T, Iwao Y, Munakata A, Fukuda S, Matsumoto T, Oshitani N, Hiwatashi N, Oriuchi T, Kitahora T, Utsunomiya T, Saitoh Y, Suzuki Y, Nakajima M. Source: European Journal of Gastroenterology & Hepatology. 2003 February; 15(2): 1517. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560759&dopt=Abstract

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Differences in P-glycoprotein-170 expression and activity between Crohn's disease and ulcerative colitis. Author(s): Yacyshyn B, Maksymowych W, Bowen-Yacyshyn MB. Source: Human Immunology. 1999 August; 60(8): 677-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439313&dopt=Abstract

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Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Author(s): Arihiro S, Ohtani H, Suzuki M, Murata M, Ejima C, Oki M, Kinouchi Y, Fukushima K, Sasaki I, Nakamura S, Matsumoto T, Torii A, Toda G, Nagura H. Source: Pathology International. 2002 May-June; 52(5-6): 367-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100519&dopt=Abstract

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Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation. Author(s): Jenkins D, Seth R, Kummer JA, Scott BB, Hawkey CJ, Robins RA. Source: The Journal of Pathology. 2000 February; 190(2): 184-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10657017&dopt=Abstract

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Differentiation between intestinal tuberculosis and Crohn's disease in endoscopic biopsy specimens by polymerase chain reaction. Author(s): Gan HT, Chen YQ, Ouyang Q, Bu H, Yang XY. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1446-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094863&dopt=Abstract

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Differentiation between ulcerative colitis and Crohn's disease by a quantitative immunohistochemical evaluation of T lymphocytes, neutrophils, histiocytes and mast cells. Author(s): Sasaki Y, Tanaka M, Kudo H. Source: Pathology International. 2002 April; 52(4): 277-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031083&dopt=Abstract

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Diffuse small bowel Crohn's disease treated with side-to-side isoperistaltic strictureplasty: report of two cases and description of a variation of the original technique. Author(s): Sommariva A, Angriman I, Ruffolo C, Barollo M, D'Amico DF. Source: Surgery Today. 2002; 32(7): 642-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111525&dopt=Abstract

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Dimethylsulfoxide for renal dysfunction caused by systemic amyloidosis complicating Crohn's disease. Author(s): Iwakiri R, Sakemi T, Fujimoto K. Source: Gastroenterology. 1999 October; 117(4): 1031-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10576978&dopt=Abstract

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Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease. Author(s): Stockbrugger RW, Schoon EJ, Bollani S, Mills PR, Israeli E, Landgraf L, Felsenberg D, Ljunghall S, Nygard G, Persson T, Graffner H, Bianchi Porro G, Ferguson A. Source: Alimentary Pharmacology & Therapeutics. 2002 August; 16(8): 1519-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182752&dopt=Abstract

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Discussion on appendectomy is followed by increased risk of Crohn's disease. Author(s): Silen W. Source: Gastroenterology. 2003 September; 125(3): 997; Author Reply 997. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974265&dopt=Abstract

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Discussion on predictors of response to infliximab in patients with Crohn's disease. Author(s): Hommes D. Source: Gastroenterology. 2003 June; 124(7): 2002-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812196&dopt=Abstract

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Disseminated cytomegalovirus infection in Crohn's disease following anti-tumour necrosis factor therapy. Author(s): Helbling D, Breitbach TH, Krause M. Source: European Journal of Gastroenterology & Hepatology. 2002 December; 14(12): 1393-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468964&dopt=Abstract

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Distant cutaneous manifestation of Crohn's disease presenting as a granulomatous erysipelas-like lesion. Author(s): Dippel E, Rosenberger A, Zouboulis CC. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1999 January; 12(1): 65-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10188155&dopt=Abstract

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Distribution and colocalization of nitric oxide synthase and calretinin in myenteric neurons of developing, aging, and Crohn's disease human small intestine. Author(s): Belai A, Burnstock G. Source: Digestive Diseases and Sciences. 1999 August; 44(8): 1579-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10492135&dopt=Abstract

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DNA variants in cytokine and NOD2 genes, exposures to infections and risk for Crohn's disease. Author(s): Amre DK, Seidman EG. Source: Paediatric and Perinatal Epidemiology. 2003 July; 17(3): 302-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839543&dopt=Abstract

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Does month of birth affect risk of Crohn's disease in childhood and adolescence? Author(s): Sorensen HT, Pedersen L, Norgard B, Fonager K, Rothman KJ. Source: Bmj (Clinical Research Ed.). 2001 October 20; 323(7318): 907. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668136&dopt=Abstract

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Does the failure to acquire helminthic parasites predispose to Crohn's disease? Author(s): Elliott DE, Urban JF JR, Argo CK, Weinstock JV. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2000 September; 14(12): 1848-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10973934&dopt=Abstract

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Does the initial location of Crohn's disease have an influence on the time-to-relapse in patients under maintenance treatment with oral mesalamine? Author(s): Bresci G, Parisi G, Bertoni M, Masolino P, Scatena F, Capria A. Source: Journal of Clinical Gastroenterology. 2000 September; 31(2): 147-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10993432&dopt=Abstract

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Doppler enhancement after intravenous levovist injection in Crohn's disease. Author(s): Di Sabatino A, Fulle I, Ciccocioppo R, Ricevuti L, Tinozzi FP, Tinozzi S, Campani R, Corazza GR. Source: Inflammatory Bowel Diseases. 2002 July; 8(4): 251-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131608&dopt=Abstract

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Dose ranging pharmacokinetic trial of high-dose alicaforsen (intercellular adhesion molecule-1 antisense oligodeoxynucleotide) (ISIS 2302) in active Crohn's disease. Author(s): Yacyshyn BR, Barish C, Goff J, Dalke D, Gaspari M, Yu R, Tami J, Dorr FA, Sewell KL. Source: Alimentary Pharmacology & Therapeutics. 2002 October; 16(10): 1761-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269969&dopt=Abstract

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Dose-effect of interleukin-10 and its immunoregulatory role in Crohn's disease. Author(s): Schmit A, Carol M, Robert F, Bontems P, Houben JJ, Van Gossum A, Goldman M, Mascart F. Source: Eur Cytokine Netw. 2002 July-September; 13(3): 298-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231473&dopt=Abstract

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Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease. Author(s): Yacyshyn BR, Chey WY, Goff J, Salzberg B, Baerg R, Buchman AL, Tami J, Yu R, Gibiansky E, Shanahan WR; ISIS 2302-CS9 Investigators. Source: Gut. 2002 July; 51(1): 30-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077088&dopt=Abstract

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Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease. Author(s): Akobeng AK, Miller V, Stanton J, Elbadri AM, Thomas AG. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 January; 30(1): 78-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10630444&dopt=Abstract

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Down syndrome and Crohn's disease: an extremely rare association. Author(s): Persic M, Dessardo S, Subat-Dezulovic M, Ahel V, Rozmanic V. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 October; 43(5): 519-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737719&dopt=Abstract

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DPP IV and mental depression in Crohn's disease. Author(s): Rose M, Walter OB, Fliege H, Hildebrandt M, Monnikes H, Klapp BF. Source: Advances in Experimental Medicine and Biology. 2003; 524: 321-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675254&dopt=Abstract

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Drug utilization study in patients with Crohn's disease in Spain. Author(s): Estiarte R, Juan J, Colome E, Artes M, Jimenez FJ. Source: European Journal of Gastroenterology & Hepatology. 2003 April; 15(4): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655254&dopt=Abstract

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Duodenal Crohn's disease. Author(s): Kimmins MH, Billingham RP. Source: Techniques in Coloproctology. 2001 April; 5(1): 9-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793253&dopt=Abstract

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Dysphagia in Crohn's disease: a diagnostic challenge. Author(s): Knoblauch C, Netzer P, Scheurer U, Seibold F. Source: Dig Liver Dis. 2002 September; 34(9): 660-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405254&dopt=Abstract

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Dysplasia and colorectal cancer in Crohn's disease. Author(s): Ullman TA. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5 Suppl): S75-8; Discussion S94-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702970&dopt=Abstract

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Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn's disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy? The Infliximab User Group. Author(s): Mortimore M, Gibson PR, Selby WS, Radford-Smith GL, Florin TH; Schering Plough (Australia). Source: Internal Medicine Journal. 2001 April; 31(3): 146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11478343&dopt=Abstract

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Early cancer in gastric Crohn's disease. Author(s): Estlein D, Ohana G, Weil R, Rath-Wolfson L, Wolloch Y. Source: Isr Med Assoc J. 2001 May; 3(5): 379-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11411206&dopt=Abstract

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Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype. Author(s): Louis E, Michel V, Hugot JP, Reenaers C, Fontaine F, Delforge M, El Yafi F, Colombel JF, Belaiche J. Source: Gut. 2003 April; 52(4): 552-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631668&dopt=Abstract

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Early environmental factors may have role in both Crohn's disease and gastric carcinoma. Author(s): Morris DL, Montgomery SM. Source: Bmj (Clinical Research Ed.). 2000 November 18; 321(7271): 1291. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11185762&dopt=Abstract

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Early phase mantle cell lymphoma: macroscopic similarities to terminal ileal Crohn's disease. Author(s): Hurlstone DP. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1577-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094901&dopt=Abstract

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Effect of Crohn's disease on bone metabolism in vitro: a role for interleukin-6. Author(s): Sylvester FA, Wyzga N, Hyams JS, Gronowicz GA. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 April; 17(4): 695-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918227&dopt=Abstract

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Effect of enteral nutrition on antioxidant enzyme systems and inflammation in paediatric Crohn's disease. Author(s): Phylactos AC, Fasoula IN, Arnaud-Battandier F, Walker-Smith JA, Fell JM. Source: Acta Paediatrica (Oslo, Norway : 1992). 2001 August; 90(8): 883-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529536&dopt=Abstract

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Effect of fecal diversion alone on perianal Crohn's disease. Author(s): Yamamoto T, Allan RN, Keighley MR. Source: World Journal of Surgery. 2000 October; 24(10): 1258-62; Discussion 1262-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11071472&dopt=Abstract

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Effect of food on the pharmacokinetics of budesonide controlled ileal release capsules in patients with active Crohn's disease. Author(s): Lundin P, Naber T, Nilsson M, Edsbacker S. Source: Alimentary Pharmacology & Therapeutics. 2001 January; 15(1): 45-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11136277&dopt=Abstract

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Effect of steroids on energy expenditure and substrate oxidation in women with Crohn's disease. Author(s): Al-Jaouni R, Schneider SM, Piche T, Rampal P, Hebuterne X. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2843-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425558&dopt=Abstract

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Effector Th-1 cells with cytotoxic function in the intestinal lamina propria of patients with Crohn's disease. Author(s): Mariani P, Bachetoni A, D'Alessandro M, Lomanto D, Mazzocchi P, Speranza V. Source: Digestive Diseases and Sciences. 2000 October; 45(10): 2029-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11117579&dopt=Abstract

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Effects of anti-tumour necrosis factor-alpha therapy on the quality of life in Crohn's disease. Author(s): van Balkom BP, Schoon EJ, Stockbrugger RW, Wolters FL, van Hogezand RA, van Deventer SJ, Oldenburg B, van Dullemen HM, Russel MG. Source: Alimentary Pharmacology & Therapeutics. 2002 June; 16(6): 1101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030951&dopt=Abstract

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Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis. Author(s): Odes HS, Fich A, Reif S, Halak A, Lavy A, Keter D, Eliakim R, Paz J, Broide E, Niv Y, Ron Y, Villa Y, Arber N, Gilat T. Source: Digestive Diseases and Sciences. 2001 August; 46(8): 1717-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508673&dopt=Abstract

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Efficacy and safety of repeated infliximab infusions for Crohn's disease: 1-year clinical experience. Author(s): Cohen RD. Source: Inflammatory Bowel Diseases. 2001 May; 7 Suppl 1: S17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380038&dopt=Abstract

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Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Author(s): Rutgeerts P, D'Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL, Schaible TF, Van Deventer SJ. Source: Gastroenterology. 1999 October; 117(4): 761-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500056&dopt=Abstract

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Efficacy and tolerability of a low microparticle diet in a double blind, randomized, pilot study in Crohn's disease. Author(s): Lomer MC, Harvey RS, Evans SM, Thompson RP, Powell JJ. Source: European Journal of Gastroenterology & Hepatology. 2001 February; 13(2): 1016. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246607&dopt=Abstract

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Efficacy of parenteral methotrexate in refractory Crohn's disease. Author(s): Chong RY, Hanauer SB, Cohen RD. Source: Alimentary Pharmacology & Therapeutics. 2001 January; 15(1): 35-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11136276&dopt=Abstract

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Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover proteins, and radiologic and endoscopic findings. Author(s): Asakura H, Yao T, Matsui T, Koganei K, Fukushima T, Takazoe M, Hobara R, Nakano H, Okamura S, Matsueda K, Kashida H, Makiyama K, Hiwatashi N, Kashiwagi K, Hibi T. Source: Journal of Gastroenterology and Hepatology. 2001 July; 16(7): 763-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446884&dopt=Abstract

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Elemental diet in the treatment of orofacial Crohn's disease. Author(s): Cameron EA, Middleton SJ. Source: Gut. 2003 January; 52(1): 143. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477777&dopt=Abstract

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Elevated antibody responses in patients with Crohn's disease against a 14-kDa secreted protein purified from Mycobacterium avium subsp. paratuberculosis. Author(s): Olsen I, Wiker HG, Johnson E, Langeggen H, Reitan LJ. Source: Scandinavian Journal of Immunology. 2001 February; 53(2): 198-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11169225&dopt=Abstract

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Enhanced production of IL-8 in chronic but not in early ileal lesions of Crohn's disease (CD). Author(s): Brandt E, Colombel JF, Ectors N, Gambiez L, Emilie D, Geboes K, Capron M, Desreumaux P. Source: Clinical and Experimental Immunology. 2000 November; 122(2): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11091272&dopt=Abstract

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Enteral and parenteral nutrition therapy for Crohn's disease. Author(s): Tsujikawa T, Andoh A, Fujiyama Y. Source: Current Pharmaceutical Design. 2003; 9(4): 323-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570824&dopt=Abstract

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Enteral nutrition in children with Crohn's disease. Author(s): Heuschkel RB. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 November; 31(5): 575. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144448&dopt=Abstract

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Enteral nutrition in Crohn's disease in childhood. Author(s): Walker-Smith JA. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 January; 32(1): 107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176338&dopt=Abstract

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Enteral nutrition in Crohn's disease: fat in the formula. Author(s): Gorard DA. Source: European Journal of Gastroenterology & Hepatology. 2003 February; 15(2): 1158. Erratum In: Eur J Gastroenterol Hepatol. 2003 April; 15(4): 459. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560753&dopt=Abstract

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Enteral nutritional supplementation and the maintenance of permission in Crohn's disease. Author(s): Akobeng AK. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 May; 34(5): 572-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078659&dopt=Abstract

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Enteral nutritional therapy for inducing remission of Crohn's disease. Author(s): Zachos M, Tondeur M, Griffiths AM. Source: Cochrane Database Syst Rev. 2001; (3): Cd000542. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11686966&dopt=Abstract

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Enteric glial cells. An upstream target for induction of necrotizing enterocolitis and Crohn's disease? Author(s): Bush TG. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 2002 February; 24(2): 130-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835277&dopt=Abstract

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Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, doubleblind, placebo-controlled trial. Author(s): Hawkes ND, Richardson C, Ch'Ng CL, Green JT, Evans BK, Williams J, Rhodes P, Rhodes J, Swift GL, Thomas GA, Hawthorne AB, Kingham JG, Mayberry JF. Source: Alimentary Pharmacology & Therapeutics. 2001 December; 15(12): 1867-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11736716&dopt=Abstract

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Enteroclysis and spiral CT examination in diagnosis and evaluation of small bowel Crohn's disease. Author(s): Mako EK, Mester AR, Tarjan Z, Karlinger K, Toth G. Source: European Journal of Radiology. 2000 September; 35(3): 168-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11000559&dopt=Abstract

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Enteroclysis in children with Crohn's disease. Author(s): Antes G. Source: European Radiology. 2001; 11(11): 2341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702182&dopt=Abstract

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Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease? Author(s): Cornet A, Savidge TC, Cabarrocas J, Deng WL, Colombel JF, Lassmann H, Desreumaux P, Liblau RS. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 November 6; 98(23): 13306-11. Epub 2001 October 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687633&dopt=Abstract

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Enterotachogram analysis to distinguish irritable bowel syndrome from Crohn's disease. Author(s): Craine BL, Silpa ML, O'Toole CJ. Source: Digestive Diseases and Sciences. 2001 September; 46(9): 1974-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575452&dopt=Abstract

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Enterovesical fistulas complicating Crohn's disease: clinicopathological features and management. Author(s): Yamamoto T, Keighley MR. Source: International Journal of Colorectal Disease. 2000 August; 15(4): 211-5; Discussion 216-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11008720&dopt=Abstract

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Environmental risk factors and Crohn's disease: a population-based, case-control study in Spain. Author(s): Sicilia B, Lopez Miguel C, Arribas F, Lopez Zaborras J, Sierra E, Gomollon F. Source: Dig Liver Dis. 2001 December; 33(9): 762-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838611&dopt=Abstract

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Erosive arthritis in juvenile onset Crohn's disease. Author(s): el Maghraoui A, Aouragh A, Hachim M, Toloune F, Ohayon V, Archane MI. Source: Clin Exp Rheumatol. 2000 July-August; 18(4): 541. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10949743&dopt=Abstract

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Essential fatty acid status in paediatric Crohn's disease: relationship with disease activity and nutritional status. Author(s): Trebble TM, Wootton SA, May A, Erlewyn-Lajeunesse MD, Chakraborty A, Mullee MA, Stroud MA, Beattie RM. Source: Alimentary Pharmacology & Therapeutics. 2003 August 15; 18(4): 433-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940929&dopt=Abstract

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Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Author(s): Sandborn WJ, Hanauer SB, Katz S, Safdi M, Wolf DG, Baerg RD, Tremaine WJ, Johnson T, Diehl NN, Zinsmeister AR. Source: Gastroenterology. 2001 November; 121(5): 1088-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11677200&dopt=Abstract

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Etanercept in the treatment of active refractory Crohn's disease: a single-center pilot trial. Author(s): D'Haens G, Swijsen C, Noman M, Lemmens L, Ceuppens J, Agbahiwe H, Geboes K, Rutgeerts P. Source: The American Journal of Gastroenterology. 2001 September; 96(9): 2564-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569676&dopt=Abstract

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Etiology of Crohn's disease: the role of Mycobacterium avium paratuberculosis. Author(s): El-Zaatari FA, Osato MS, Graham DY. Source: Trends in Molecular Medicine. 2001 June; 7(6): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378513&dopt=Abstract

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Etiopathogenesis of pediatric Crohn's disease. Biologic pathways based on interactions between genetic and environmental factors. Author(s): K Amre D, G Seidman E. Source: Medical Hypotheses. 2003 March; 60(3): 344-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581610&dopt=Abstract

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Evaluation of oral budesonide for treatment of mild and moderate exacerbations of Crohn's disease in children. Author(s): Levine A, Broide E, Stein M, Bujanover Y, Weizman Z, Dinari G, Pacht A, Branski D, Zahavi I. Source: The Journal of Pediatrics. 2002 January; 140(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815767&dopt=Abstract

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Evaluation of serologic disease markers in a population-based cohort of patients with ulcerative colitis and Crohn's disease. Author(s): Sandborn WJ, Loftus EV Jr, Colombel JF, Fleming KA, Seibold F, Homburger HA, Sendid B, Chapman RW, Tremaine WJ, Kaul DK, Wallace J, Harmsen WS, Zinsmeister AR, Targan SR. Source: Inflammatory Bowel Diseases. 2001 August; 7(3): 192-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515844&dopt=Abstract

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Evaluation of serological markers to differentiate between ulcerative colitis and Crohn's disease: pANCA, ASCA and agglutinating antibodies to anaerobic coccoid rods. Author(s): Linskens RK, Mallant-Hent RC, Groothuismink ZM, Bakker-Jonges LE, van de Merwe JP, Hooijkaas H, von Blomberg BM, Meuwissen SG. Source: European Journal of Gastroenterology & Hepatology. 2002 September; 14(9): 1013-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352222&dopt=Abstract

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Evidence for separate disease phenotypes in intestinal Crohn's disease. Author(s): Borley NR, Mortensen NJ, Chaudry MA, Mohammed S, Clarke T, Jewell DP. Source: The British Journal of Surgery. 2002 February; 89(2): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856134&dopt=Abstract

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Evidence for the clinical use of infliximab in Crohn's disease. Author(s): Turner SM, Probert CS. Source: Rom J Gastroenterol. 2003 March; 12(1): 2-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673372&dopt=Abstract

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Evolutive pattern in Crohn's disease: a simplified index using clinical parameters predicts obstructive behaviour. Author(s): Hinojosa J, Nos P, Ramirez JJ, Hoyos M, Moles JR, Ponce J, Berenguer J. Source: European Journal of Gastroenterology & Hepatology. 2001 March; 13(3): 245-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293443&dopt=Abstract

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Evolving medical therapies for Crohn's disease. Author(s): Mahadevan U, Sandborn WJ. Source: Current Gastroenterology Reports. 2001 December; 3(6): 471-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696284&dopt=Abstract

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Exacerbation of Crohn's disease after insertion of a levonorgestrel intrauterine system: a case report. Author(s): Wakeman J. Source: The Journal of Family Planning and Reproductive Health Care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists. 2003 July; 29(3): 154. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885311&dopt=Abstract

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Exacerbation of Mycobacterium tuberculosis enteritis masquerading as Crohn's disease after treatment with a tumor necrosis factor-alpha inhibitor. Author(s): Wagner TE, Huseby ES, Huseby JS. Source: The American Journal of Medicine. 2002 January; 112(1): 67-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812409&dopt=Abstract

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Exclusion of linkage of Crohn's disease to previously reported regions on chromosomes 12, 7, and 3 in the Belgian population indicates genetic heterogeneity. Author(s): Vermeire S, Peeters M, Vlietinck R, Parkes M, Satsangi J, Jewell D, Rutgeerts P. Source: Inflammatory Bowel Diseases. 2000 August; 6(3): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961588&dopt=Abstract

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Exercise program effects on one woman with multiple sclerosis, Crohn's disease, fibromyalgia syndrome, and clinical depression. Author(s): Karper WB. Source: N C Med J. 2001 January-February; 62(1): 14-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198092&dopt=Abstract

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Existence of variant gamma delta T cells in Crohn's disease. Author(s): Ishiguro Y, Kanazawa H, Yamagata K, Sakuraba H, Munakata A. Source: Digestion. 2001; 63 Suppl 1: 48-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173910&dopt=Abstract

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Expression of clusterin in Crohn's disease of the terminal ileum. Author(s): Gassler N, Autschbach F, Heuschen G, Witzgall R, Otto HF, Obermuller N. Source: Histology and Histopathology. 2001 July; 16(3): 755-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510965&dopt=Abstract

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Expression of mRNA for glucocorticoid receptors in peripheral blood mononuclear cells of patients with Crohn's disease. Author(s): Hori T, Watanabe K, Miyaoka M, Moriyasu F, Onda K, Hirano T, Oka K. Source: Journal of Gastroenterology and Hepatology. 2002 October; 17(10): 1070-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201866&dopt=Abstract

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Expression of the T-cell chemoattractant chemokine lymphotactin in Crohn's disease. Author(s): Middel P, Thelen P, Blaschke S, Polzien F, Reich K, Blaschke V, Wrede A, Hummel KM, Gunawan B, Radzun HJ. Source: American Journal of Pathology. 2001 November; 159(5): 1751-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696436&dopt=Abstract

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Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study. Author(s): Reinisch W, Nahavandi H, Santella R, Zhang Y, Gasche C, Moser G, Waldhor T, Gangl A, Vogelsang H, Knobler R. Source: Alimentary Pharmacology & Therapeutics. 2001 September; 15(9): 1313-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552901&dopt=Abstract

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Extraintestinal Crohn's disease: case report and review of the literature. Author(s): Ulnick KM, Perkins J. Source: Ear, Nose, & Throat Journal. 2001 February; 80(2): 97-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233351&dopt=Abstract

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Extraintestinal Hodgkin's disease in a patient with Crohn's disease. Author(s): Calvo-Villas JM, Ramirez Sanchez MJ, Cuesta Tovar J, Garcia C. Source: Southern Medical Journal. 2003 June; 96(6): 632. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938798&dopt=Abstract

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Factors affecting the incidence of postoperative septic complications and recurrence after strictureplasty for jejunoileal Crohn's disease. Author(s): Yamamoto T, Keighley MR. Source: American Journal of Surgery. 1999 September; 178(3): 240-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10527447&dopt=Abstract

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Faecal calprotectin: a bright future for assessing disease activity in Crohn's disease. Author(s): Gaya DR, Mackenzie JF. Source: Qjm : Monthly Journal of the Association of Physicians. 2002 September; 95(9): 557-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205332&dopt=Abstract

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Familial Crohn's disease in single or multiple first-degree relatives. Author(s): Freeman HJ. Source: Journal of Clinical Gastroenterology. 2002 July; 35(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12080219&dopt=Abstract

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Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease. Author(s): Sutton CL, Yang H, Li Z, Rotter JI, Targan SR, Braun J. Source: Gut. 2000 January; 46(1): 58-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10601056&dopt=Abstract

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Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study. Author(s): Annese V, Andreoli A, Andriulli A, Dinca R, Gionchetti P, Latiano A, Lombardi G, Piepoli A, Poulain D, Sendid B, Colombel JF. Source: The American Journal of Gastroenterology. 2001 August; 96(8): 2407-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513182&dopt=Abstract

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Fatal evolution of systemic lupus erythematosus associated with Crohn's disease. Author(s): Chebli JM, Gaburri PD, de Souza AF, Dias KV, Cimino KO, de CarvalhoFilho RJ, Lucca FA. Source: Arquivos De Gastroenterologia. 2000 October-December; 37(4): 224-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469224&dopt=Abstract

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Fate of the rectum and ileal recurrence rates after total colectomy for Crohn's disease. Author(s): Yamamoto T, Keighley MR. Source: World Journal of Surgery. 2000 January; 24(1): 125-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10594216&dopt=Abstract

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Fate of the rectum in patients undergoing total colectomy for Crohn's disease. Author(s): Cattan P, Bonhomme N, Panis Y, Lemann M, Coffin B, Bouhnik Y, Allez M, Sarfati E, Valleur P. Source: The British Journal of Surgery. 2002 April; 89(4): 454-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952587&dopt=Abstract

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Fecal alpha 1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn's disease of the distal ileum. Author(s): Biancone L, Fantini M, Tosti C, Bozzi R, Vavassori P, Pallone F. Source: European Journal of Gastroenterology & Hepatology. 2003 March; 15(3): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610321&dopt=Abstract

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Fecal calprotectin in Crohn's disease: new family ties. Author(s): Tamboli CP, Richard F, Colombel JF. Source: Gastroenterology. 2003 June; 124(7): 1972-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806631&dopt=Abstract

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Female workforce participation, use of oral contraceptives, and the sex ratio of Crohn's disease incidence. Author(s): Alic M. Source: The American Journal of Gastroenterology. 2000 January; 95(1): 328-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638625&dopt=Abstract

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Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease. Author(s): Lomer MC, Thompson RP, Powell JJ. Source: The Proceedings of the Nutrition Society. 2002 February; 61(1): 123-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002786&dopt=Abstract

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First reported case of colitis cystica profunda in association with Crohn's disease. Author(s): Madan A, Minocha A. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2472-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358281&dopt=Abstract

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Fistulas to the urinary system in Crohn's disease: clinical features and outcomes. Author(s): Solem CA, Loftus EV Jr, Tremaine WJ, Pemberton JH, Wolff BG, Sandborn WJ. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2300-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358248&dopt=Abstract

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Focally enhanced gastritis in children with Crohn's disease and ulcerative colitis. Author(s): Sharif F, McDermott M, Dillon M, Drumm B, Rowland M, Imrie C, Kelleher S, Harty S, Bourke B. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1415-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094859&dopt=Abstract

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Fracture risk in patients with celiac Disease, Crohn's disease, and ulcerative colitis: a nationwide follow-up study of 16,416 patients in Denmark. Author(s): Vestergaard P, Mosekilde L. Source: American Journal of Epidemiology. 2002 July 1; 156(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076883&dopt=Abstract

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Fracture risk is increased in Crohn's disease, but not in ulcerative colitis. Author(s): Vestergaard P, Krogh K, Rejnmark L, Laurberg S, Mosekilde L. Source: Gut. 2000 February; 46(2): 176-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10644310&dopt=Abstract

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Free perforation in Crohn's disease. Author(s): Werbin N, Haddad R, Greenberg R, Karin E, Skornick Y. Source: Isr Med Assoc J. 2003 March; 5(3): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725136&dopt=Abstract

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Free perforation in Crohn's disease: review of the Japanese literature. Author(s): Ikeuchi H, Yamamura T. Source: Journal of Gastroenterology. 2002; 37(12): 1020-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522533&dopt=Abstract

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Frequency of continuing mucosal inflammation in clinically inactive Crohn's disease. Author(s): Arnott ID, Drummond HE, Ghosh S. Source: Scott Med J. 2001 October; 46(5): 136-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771492&dopt=Abstract

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Frequently relapsing Crohn's disease is characterized by persistent elevation in interleukin-6 and soluble interleukin-2 receptor serum levels during remission. Author(s): Van Kemseke C, Belaiche J, Louis E. Source: International Journal of Colorectal Disease. 2000 August; 15(4): 206-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11008719&dopt=Abstract

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From extracellular to intracellular targets, inhibiting MAP kinases in treatment of Crohn's disease. Author(s): Van Den Blink B, Ten Hove T, Van Den Brink GR, Peppelenbosch MP, Van Deventer SJ. Source: Annals of the New York Academy of Sciences. 2002 November; 973: 349-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485892&dopt=Abstract

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From illness comes strength. A nursing student with Crohn's disease tells her story. Author(s): Miller TS. Source: Imprint. 2001 September-October; 48(4): 45, 75. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152539&dopt=Abstract

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Fruit pit obstruction leading to the diagnosis of Crohn's disease. Author(s): Kaufman D, Lazinger M, Fogel S, Dutta SK. Source: American Journal of Surgery. 2001 November; 182(5): 530. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754864&dopt=Abstract

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Funding the new biologics--a health economic critique of the CCOHTA report: infliximab for the treatment of Crohn's disease. Author(s): Mitton CR; Canadian Coordinating Office for Health Technology Assessment. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 December; 16(12): 873-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522479&dopt=Abstract

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Further evidence of the absence of measles virus genome sequence in full thickness intestinal specimens from patients with Crohn's disease. Author(s): Afzal MA, Armitage E, Ghosh S, Williams LC, Minor PD. Source: Journal of Medical Virology. 2000 November; 62(3): 377-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055248&dopt=Abstract

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Gallbladder carcinoma complicating Crohn's disease. Author(s): Ogawa H, Funayama Y, Naito H, Fukushima K, Shibata C, Matsuno S, Sasaki I. Source: The American Journal of Gastroenterology. 2001 January; 96(1): 263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197277&dopt=Abstract

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Gallstone ileus and Crohn's disease without biliary-enteric fistula: report of a unique case. Author(s): Almogy G, Bauer JJ, Venturero M, Presen DH. Source: The Mount Sinai Journal of Medicine, New York. 2000 March; 67(2): 159-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10747373&dopt=Abstract

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Gastric and small bowel Crohn's disease assessed with leukocytes-Tc(99m) scintigraphy. Author(s): Charron M, Di Lorenzo C, Kocoshis S. Source: Pediatric Surgery International. 1999; 15(7): 500-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525909&dopt=Abstract

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Gastric Crohn's disease and SAPHO syndrome. Author(s): Girelli CM, Scarpellini M. Source: Clin Exp Rheumatol. 2001 May-June; 19(3): 356. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407099&dopt=Abstract

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Gastric outlet obstruction and pulmonary infiltrate in a patient with Crohn's disease: successful treatment by Billroth-II-resection. Author(s): Voderholzer WA, Zietz C, Feucht HE, Heldwein W, Hallfeldt H, Huber RM, Loeschke K. Source: Zeitschrift Fur Gastroenterologie. 2000 August; 38(8): 637-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11031788&dopt=Abstract

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Gastrocolic fistula in Crohn's disease. Author(s): Hokama A, Sugama R, Kinjo F, Saito A. Source: Gastrointestinal Endoscopy. 1999 September; 50(3): 387. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10462661&dopt=Abstract

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Gastrocolic fistulization in Crohn's disease: a case report and a review of the literature. Author(s): Khanna MP, Gordon PH. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2000 February; 43(1): 53-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714259&dopt=Abstract

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Gastroduodenal Crohn's disease: medical management. Author(s): Tremaine WJ. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 127-8; Discussion 131. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769447&dopt=Abstract

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Gastrointestinal: Crohn's disease of the oesophagus. Author(s): Kimber RD, Roberts-Thomson IC. Source: Journal of Gastroenterology and Hepatology. 2000 August; 15(8): 959. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022841&dopt=Abstract

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Gastrostomy placement in patients with Crohn's disease. Author(s): Nightingale J. Source: European Journal of Gastroenterology & Hepatology. 2000 October; 12(10): 10735. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11057451&dopt=Abstract

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Gender, age, and body weight are the major predictive factors for bone mineral density in Crohn's disease: a case-control cross-sectional study of 113 patients. Author(s): Andreassen H, Hylander E, Rix M. Source: The American Journal of Gastroenterology. 1999 March; 94(3): 824-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086673&dopt=Abstract

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Gender-related differences in the clinical course of Crohn's disease. Author(s): Wagtmans MJ, Verspaget HW, Lamers CB, van Hogezand RA. Source: The American Journal of Gastroenterology. 2001 May; 96(5): 1541-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11374696&dopt=Abstract

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Gene expression of group II phospholipase A2 in intestine in Crohn's disease. Author(s): Haapamaki MM, Gronroos JM, Nurmi H, Alanen K, Nevalainen TJ. Source: The American Journal of Gastroenterology. 1999 March; 94(3): 713-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086656&dopt=Abstract

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Genes, microbes, and T cells--new therapeutic targets in Crohn's disease. Author(s): Elson CO. Source: The New England Journal of Medicine. 2002 February 21; 346(8): 614-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856802&dopt=Abstract

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Genetic analyses of chromosome 12 loci in Crohn's disease. Author(s): Lesage S, Zouali H, Colombel JF, Belaiche J, Cezard JP, Tysk C, Almer S, Gassull M, Binder V, Chamaillard M, Le Gall I, Thomas G, Hugot JP. Source: Gut. 2000 December; 47(6): 787-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076876&dopt=Abstract

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Genetic polymorphisms in biotransformation enzymes in Crohn's disease: association with microsomal epoxide hydrolase. Author(s): de Jong DJ, van der Logt EM, van Schaik A, Roelofs HM, Peters WH, Naber TH. Source: Gut. 2003 April; 52(4): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631667&dopt=Abstract

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Genetic susceptibility and regulation of inflammation in Crohn's disease. Relationship with the innate immune system. Author(s): Pena AS, Penate M. Source: Rev Esp Enferm Dig. 2002 June; 94(6): 351-60. Review. English, Spanish. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432592&dopt=Abstract

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Genetic susceptibility in Crohn's disease--review of clinical studies. Author(s): Tysk C. Source: The European Journal of Surgery = Acta Chirurgica. 1998 December; 164(12): 893-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10029383&dopt=Abstract

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Genetically related Escherichia coli strains associated with Crohn's disease. Author(s): Masseret E, Boudeau J, Colombel JF, Neut C, Desreumaux P, Joly B, Cortot A, Darfeuille-Michaud A. Source: Gut. 2001 March; 48(3): 320-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171820&dopt=Abstract

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Genetics of Crohn's disease behaviour. Author(s): Louis E, Belaiche J. Source: Acta Gastroenterol Belg. 2000 October-December; 63(4): 377-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233521&dopt=Abstract

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Genomics and phenomics in Crohn's disease. Author(s): Sachar DB. Source: Gastroenterology. 2002 April; 122(4): 1161-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910366&dopt=Abstract

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Genotype-phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31. Author(s): Armuzzi A, Ahmad T, Ling KL, de Silva A, Cullen S, van Heel D, Orchard TR, Welsh KI, Marshall SE, Jewell DP. Source: Gut. 2003 August; 52(8): 1133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865271&dopt=Abstract

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Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Author(s): Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, Soule JC, Modigliani R, Touze Y, Catala P, Libersa C, Broly F. Source: Gastroenterology. 2000 June; 118(6): 1025-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833476&dopt=Abstract

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Giant cell arteritis localized to the colon associated with Crohn's disease. Author(s): Colombat M, Imbert A, Bruneval P, Chatelain D, Gontier MF. Source: Histopathology. 2001 January; 38(1): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135042&dopt=Abstract

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Giant cell myocarditis, in a patient with Crohn's disease, treated with etanercept--a tumour necrosis factor-alpha antagonist. Author(s): Nash CL, Panaccione R, Sutherland LR, Meddings JB. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 September; 15(9): 607-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573104&dopt=Abstract

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Giant inflammatory polyposis of the descending colon associated with a Crohn's disease-like colitis. Author(s): Kosugi I, Tada T, Tsutsui Y, Sato Y, Mitsui T, Itazu I. Source: Pathology International. 2002 April; 52(4): 318-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031089&dopt=Abstract

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

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GM-CSF treatment for Crohn's disease: a stimulating new therapy? Author(s): Wilk JN, Viney JL. Source: Curr Opin Investig Drugs. 2002 September; 3(9): 1291-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498002&dopt=Abstract

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Gracilis transposition in complicated perianal fistula and unhealed perineal wounds in Crohn's disease. Author(s): Rius J, Nessim A, Nogueras JJ, Wexner SD. Source: The European Journal of Surgery = Acta Chirurgica. 2000 March; 166(3): 218-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755336&dopt=Abstract

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Granulocytapheresis for Crohn's disease: a report on seven refractory patients. Author(s): Matsui T, Nishimura T, Matake H, Ohta T, Sakurai T, Yao T. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 511-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591086&dopt=Abstract

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Granulocyte elastase and systemic cytokine response after laparoscopic-assisted and open resections in Crohn's disease. Author(s): Hildebrandt U, Kessler K, Pistorius G, Lindemann W, Ecker KW, Feifel G, Menger MD. Source: Diseases of the Colon and Rectum. 1999 November; 42(11): 1480-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566539&dopt=Abstract

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Granulocyte-macrophage colony-stimulating factor for Crohn's disease. Author(s): Drumm B, Vaughan D. Source: Lancet. 2003 May 24; 361(9371): 1830; Author Reply 1830-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781575&dopt=Abstract

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Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded? Author(s): Shepherd NA. Source: Histopathology. 2002 August; 41(2): 166-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147095&dopt=Abstract

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Granulomatous aortitis presenting as an acute myocardial infarction in Crohn's disease. Author(s): Goldman MH, Akl B, Mafi S, Pastore L. Source: Circulation. 2000 December 12; 102(24): 3023-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113056&dopt=Abstract

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Granulomatous cheilitis and Crohn's disease. Author(s): Ahmad I, Owens D. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 April; 15(4): 273-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331931&dopt=Abstract

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Granulomatous lung masses in an elderly patient with inactive Crohn's disease. Author(s): Lucero PF, Frey WC, Shaffer RT, Morris MJ. Source: Inflammatory Bowel Diseases. 2001 August; 7(3): 256-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515853&dopt=Abstract

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Granulomatous osteonecrosis in Crohn's disease. Author(s): Freeman HJ, Owen D, Millan M. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 December; 14(11): 951-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11125186&dopt=Abstract

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Granulomatous pulmonary disease in a child: an unusual presentation of Crohn's disease. Author(s): Al-Binali AM, Scott B, Al-Garni A, Montgomery M, Robertson M. Source: Pediatric Pulmonology. 2003 July; 36(1): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772229&dopt=Abstract

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Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis. Author(s): Mahadeva U, Martin JP, Patel NK, Price AB. Source: Histopathology. 2002 July; 41(1): 50-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121237&dopt=Abstract

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Growth after intestinal resection for Crohn's disease in children, adolescents, and young adults. Author(s): Sentongo TA, Stettler N, Christian A, Han PD, Stallings VA, Baldassano RN. Source: Inflammatory Bowel Diseases. 2000 November; 6(4): 265-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149557&dopt=Abstract

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Growth in Crohn's disease. Author(s): Savage MO, Beattie RM, Camacho-Hubner C, Walker-Smith JA, Sanderson IR. Source: Acta Paediatr Suppl. 1999 February; 88(428): 89-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10102061&dopt=Abstract

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Growth in paediatric Crohn's disease. Author(s): Cezard JP, Touati G, Alberti C, Hugot JP, Brinon C, Czernichow P. Source: Hormone Research. 2002; 58 Suppl 1: 11-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373007&dopt=Abstract

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Growth of an IBD controversy: growth hormone and Crohn's disease. Author(s): Binion DG, Alemzadeh R. Source: Inflammatory Bowel Diseases. 2001 May; 7(2): 176-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383593&dopt=Abstract

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Growth, body composition, and nutritional status in children and adolescents with Crohn's disease. Author(s): Sentongo TA, Semeao EJ, Piccoli DA, Stallings VA, Zemel BS. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 July; 31(1): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896068&dopt=Abstract

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Gut luminal neutrophil migration is influenced by the anatomical site of Crohn's disease. Author(s): Arnott ID, Drummond HE, Ghosh S. Source: European Journal of Gastroenterology & Hepatology. 2001 March; 13(3): 239-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293442&dopt=Abstract

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Gut mucosal response to food antigens in Crohn's disease. Author(s): Van Den Bogaerde J, Cahill J, Emmanuel AV, Vaizey CJ, Talbot IC, Knight SC, Kamm MA. Source: Alimentary Pharmacology & Therapeutics. 2002 November; 16(11): 1903-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390099&dopt=Abstract

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Gut mucosal secretion of interleukin 1beta and interleukin-8 predicts relapse in clinically inactive Crohn's disease. Author(s): Arnott ID, Drummond HE, Ghosh S. Source: Digestive Diseases and Sciences. 2001 February; 46(2): 402-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281191&dopt=Abstract

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Gut peptides and elemental diet in childhood Crohn's disease. Author(s): Sagher FA, Miller V. Source: Saudi Med J. 2001 November; 22(11): 1035. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744983&dopt=Abstract

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Gynecologic aspects of Crohn's disease. Author(s): Feller ER, Ribaudo S, Jackson ND. Source: American Family Physician. 2001 November 15; 64(10): 1725-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759079&dopt=Abstract

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Haplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations. Author(s): Croucher PJ, Mascheretti S, Hampe J, Huse K, Frenzel H, Stoll M, Lu T, Nikolaus S, Yang SK, Krawczak M, Kim WH, Schreiber S. Source: European Journal of Human Genetics : Ejhg. 2003 January; 11(1): 6-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529700&dopt=Abstract

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Health-related quality of life in Crohn's disease: a prospective longitudinal study in 231 patients. Author(s): Blondel-Kucharski F, Chircop C, Marquis P, Cortot A, Baron F, Gendre JP, Colombel JF; Groupe d'Etudes Therapeutique des Affections Inflammatoires Digestives (GETAID). Source: The American Journal of Gastroenterology. 2001 October; 96(10): 2915-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693326&dopt=Abstract

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Health-related quality of life in patients with Crohn's disease: influence of surgical operation--a prospective trial. Author(s): Tillinger W, Mittermaier C, Lochs H, Moser G. Source: Digestive Diseases and Sciences. 1999 May; 44(5): 932-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10235600&dopt=Abstract

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Helicobacter pylori seroprevalence in Crohn's disease: lack of influence by pharmacological treatment. Author(s): Guslandi M, Fanti L, Testoni PA. Source: Hepatogastroenterology. 2002 September-October; 49(47): 1296-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239929&dopt=Abstract

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Helping a family to cope with the effects of Crohn's disease. Author(s): Smith S. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1999 June 9-15; 13(38): 56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10497474&dopt=Abstract

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Helping patients with Crohn's disease quit smoking. Author(s): Hilsden RJ, Hodgins DC, Timmer A, Sutherland LR. Source: The American Journal of Gastroenterology. 2000 February; 95(2): 352-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10685735&dopt=Abstract

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Hepatitis B and C virus infection in Crohn's disease. Author(s): Biancone L, Pavia M, Del Vecchio Blanco G, D'Inca R, Castiglione F, De Nigris F, Doldo P, Cosco F, Vavassori P, Bresci GP, Arrigoni A, Cadau G, Monteleone I, Rispo A, Fries T, Mallardi B, Sturniolo GC, Pallone F; Italian Group for the Study of the Colon and Rectum (GISC). Source: Inflammatory Bowel Diseases. 2001 November; 7(4): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720317&dopt=Abstract

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Hepatitis related to cytomegalovirus infection in two patients with Crohn's disease treated with azathioprine. Author(s): Castiglione F, Del Vecchio Blanco G, Rispo A, Cozzolino A, Di Girolamo E, Cappuccio D, Mazzacca G. Source: Dig Liver Dis. 2000 October; 32(7): 626-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142564&dopt=Abstract

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Hepatotoxicity associated with 6-thioguanine therapy for Crohn's disease. Author(s): Rulyak SJ, Saunders MD, Lee SD. Source: Journal of Clinical Gastroenterology. 2003 March; 36(3): 234-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590235&dopt=Abstract

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Hereditary angioneurotic edema and familial Crohn's disease. Author(s): Freeman HJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 April; 14(4): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799088&dopt=Abstract

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Hidradenitis suppurativa and Crohn's disease: response to treatment with infliximab. Author(s): Martinez F, Nos P, Benlloch S, Ponce J. Source: Inflammatory Bowel Diseases. 2001 November; 7(4): 323-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720323&dopt=Abstract

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High normal serum levels of C3 and C1 inhibitor, two acute-phase proteins belonging to the complement system, occur more frequently in patients with Crohn's disease than ulcerative colitis. Author(s): Bene L, Fust G, Fekete B, Kovacs A, Horvath L, Prohaszka Z, Miklos K, Palos G, Daha M, Farkas H, Varga L. Source: Digestive Diseases and Sciences. 2003 June; 48(6): 1186-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822883&dopt=Abstract

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High prevalence of osteoporotic vertebral fractures in patients with Crohn's disease. Author(s): Klaus J, Armbrecht G, Steinkamp M, Bruckel J, Rieber A, Adler G, Reinshagen M, Felsenberg D, von Tirpitz C. Source: Gut. 2002 November; 51(5): 654-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377802&dopt=Abstract

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High serum tumor necrosis factor-alpha levels are associated with lack of response to infliximab in fistulizing Crohn's disease. Author(s): Martinez-Borra J, Lopez-Larrea C, Gonzalez S, Fuentes D, Dieguez A, Deschamps EM, Perez-Pariente JM, Lopez-Vazquez A, de Francisco R, Rodrigo L. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2350-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358255&dopt=Abstract

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High variation of tioguanine absorption in patients with chronic active Crohn's disease. Author(s): Deibert P, Dilger K, Fischer C, Hofmann U, Nauck S, Stoelben S, Kreisel W. Source: Alimentary Pharmacology & Therapeutics. 2003 July 15; 18(2): 183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869078&dopt=Abstract

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HLA class II alleles associated with susceptibility and resistance to Crohn's disease in the Jewish population. Author(s): Gulwani-Akolkar B, Akolkar PN, Lin XY, Heresbach D, Manji R, Katz S, Yang SY, Silver J. Source: Inflammatory Bowel Diseases. 2000 May; 6(2): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833064&dopt=Abstract

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Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. Author(s): Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nunez G. Source: The Journal of Biological Chemistry. 2003 February 21; 278(8): 5509-12. Epub 2003 January 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514169&dopt=Abstract

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How does pouch construction for a final diagnosis of Crohn's disease compare with ileoproctostomy for established Crohn's proctocolitis? Author(s): Mylonakis E, Allan RN, Keighley MR. Source: Diseases of the Colon and Rectum. 2001 August; 44(8): 1137-42; Discussion 11423. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535853&dopt=Abstract

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How effective is extensive nonsurgical treatment of patients with clinically active Crohn's disease of the terminal ileum in preventing surgery? Author(s): Bemelman WA, Ivenski M, van Hogezand RA, Hermans J, Veenendaal RA, Griffioen G. Source: Digestive Surgery. 2001; 18(1): 56-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244261&dopt=Abstract

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Hydrogen peroxide enhanced ultrasound- fistulography in the assessment of enterocutaneous fistulas complicating Crohn's disease. Author(s): Maconi G, Parente F, Porro GB. Source: Gut. 1999 December; 45(6): 874-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10562586&dopt=Abstract

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Hydro-MRI in Crohn's disease: appraisal of disease activity. Author(s): Schunk K, Kern A, Oberholzer K, Kalden P, Mayer I, Orth T, Wanitschke R. Source: Investigative Radiology. 2000 July; 35(7): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10901105&dopt=Abstract

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Hyperplastic-like mucosal change in Crohn's disease: an unusual form of dysplasia? Author(s): Kilgore SP, Sigel JE, Goldblum JR. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2000 July; 13(7): 797-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912940&dopt=Abstract

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IBD5: the second Crohn's disease gene? Author(s): Brant SR. Source: Inflammatory Bowel Diseases. 2002 September; 8(5): 371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479655&dopt=Abstract

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IGF-I and procollagen alpha1(I) are coexpressed in a subset of mesenchymal cells in active Crohn's disease. Author(s): Pucilowska JB, McNaughton KK, Mohapatra NK, Hoyt EC, Zimmermann EM, Sartor RB, Lund PK. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2000 December; 279(6): G1307-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11093955&dopt=Abstract

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IL-10 therapy in Crohn's disease: at the crossroads. Treatment of Crohn's disease with the anti-inflammatory cytokine interleukin 10. Author(s): Herfarth H, Scholmerich J. Source: Gut. 2002 February; 50(2): 146-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788549&dopt=Abstract

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IL18 polymorphism is associated with an increased risk of Crohn's disease. Author(s): Tamura K, Fukuda Y, Sashio H, Takeda N, Bamba H, Kosaka T, Fukui S, Sawada K, Tamura K, Satomi M, Yamada T, Yamamura T, Yamamoto Y, Furuyama J, Okamura H, Shimoyama T. Source: Journal of Gastroenterology. 2002 November; 37 Suppl 14: 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572878&dopt=Abstract

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IL-18-binding protein expression by endothelial cells and macrophages is upregulated during active Crohn's disease. Author(s): Corbaz A, ten Hove T, Herren S, Graber P, Schwartsburd B, Belzer I, Harrison J, Plitz T, Kosco-Vilbois MH, Kim SH, Dinarello CA, Novick D, van Deventer S, Chvatchko Y. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 April 1; 168(7): 3608-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907126&dopt=Abstract

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Ileal Crohn's disease is best treated by surgery. Author(s): Farthing MJ. Source: Gut. 2002 July; 51(1): 13-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077084&dopt=Abstract

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Ileal Crohn's disease is best treated by surgery. Author(s): Windsor AC. Source: Gut. 2002 July; 51(1): 11-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077083&dopt=Abstract

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Images in clinical medicine. Fistulizing Crohn's disease. Author(s): Sanchez W, Loftus EV. Source: The New England Journal of Medicine. 2002 August 8; 347(6): 416. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167684&dopt=Abstract

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Immunogenicity of infliximab in Crohn's disease. Author(s): Hanauer SB. Source: The New England Journal of Medicine. 2003 May 22; 348(21): 2155-6; Author Reply 2155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761378&dopt=Abstract

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Immunomodulation of Crohn's Disease. Author(s): van Deventer SJ. Source: Curr Dir Autoimmun. 2000; 2: 150-66. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791454&dopt=Abstract

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Immunomodulators and "on demand" therapy with infliximab in Crohn's disease: clinical experience with 400 infusions. Author(s): Kinney T, Rawlins M, Kozarek R, France R, Patterson D. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 608-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650795&dopt=Abstract

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Immunomodulatory drugs in Crohn's disease patients with hepatitis B or C virus infection. Author(s): Biancone L, Del Vecchio Blanco G, Pallone F, Castiglione F, Bresci G, Sturniolo G; Italian Group for the Study of the Colon and Rectum. Source: Gastroenterology. 2002 February; 122(2): 593-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11845808&dopt=Abstract

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Immunosuppressive treatment of Crohn's disease with fistulae. Author(s): Zboril V, Prokopova L, Dite P, Pokorny A, Dastych M Jr, Pazourkova M. Source: Bratisl Lek Listy. 2002; 103(3): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190046&dopt=Abstract

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Improvement of arthritis and arthralgia after treatment with infliximab (Remicade) in a German prospective, open-label, multicenter trial in refractory Crohn's disease. Author(s): Herfarth H, Obermeier F, Andus T, Rogler G, Nikolaus S, Kuehbacher T, Schreiber S. Source: The American Journal of Gastroenterology. 2002 October; 97(10): 2688-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385472&dopt=Abstract

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In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis. Author(s): Bridger S, Lee JC, Bjarnason I, Jones JE, Macpherson AJ. Source: Gut. 2002 July; 51(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077086&dopt=Abstract

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In situ identification of mycobacteria in Crohn's disease patient tissue using confocal scanning laser microscopy. Author(s): Naser SA, Shafran I, Schwartz D, El-Zaatari F, Biggerstaff J. Source: Molecular and Cellular Probes. 2002 February; 16(1): 41-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005446&dopt=Abstract

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In vitro analysis of interferon gamma (IFN-gamma) and interleukin-12 (IL-12) production and their effects in ileal Crohn's disease. Author(s): Colpaert S, Vastraelen K, Liu Z, Maerten P, Shen C, Penninckx F, Geboes K, Rutgeerts P, Ceuppens JL. Source: Eur Cytokine Netw. 2002 October-December; 13(4): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517728&dopt=Abstract

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Incidence of paediatric Crohn's disease in Stockholm, Sweden. Author(s): Askling J, Grahnquist L, Ekbom A, Finkel Y. Source: Lancet. 1999 October 2; 354(9185): 1179. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10513717&dopt=Abstract

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Increased expression of interleukin-12 receptor beta(2) on lamina propria mononuclear cells of patients with active Crohn's disease. Author(s): Stallmach A, Marth T, Adrian N, Wittig BM, Ecker KW, Schilling M, Zeitz M. Source: International Journal of Colorectal Disease. 2002 September; 17(5): 303-10. Epub 2002 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172923&dopt=Abstract

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Increased levels of lipoprotein (a) in Crohn's disease: a relation to thrombosis? Author(s): Koutroubakis IE, Malliaraki N, Vardas E, Ganotakis E, Margioris AN, Manousos ON, Kouroumalis EA. Source: European Journal of Gastroenterology & Hepatology. 2001 December; 13(12): 1415-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742189&dopt=Abstract

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Increased serum bone sialoprotein concentrations in patients with Crohn's disease. Author(s): Faust D, Menge F, Armbruster FP, Lembcke B, Stein J. Source: Zeitschrift Fur Gastroenterologie. 2003 March; 41(3): 243-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664344&dopt=Abstract

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Increased urinary F2-isoprostanes in patients with Crohn's disease. Author(s): Cracowski JL, Bonaz B, Bessard G, Bessard J, Anglade C, Fournet J. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808977&dopt=Abstract

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Increasing incidence of both juvenile-onset Crohn's disease and ulcerative colitis in Scotland. Author(s): Armitage E, Drummond HE, Wilson DC, Ghosh S. Source: European Journal of Gastroenterology & Hepatology. 2001 December; 13(12): 1439-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742192&dopt=Abstract

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Indications and results of surgery in patients with Crohn's disease with onset under 10 years of age: a series of 18 patients. Author(s): Dokucu AI, Sarnacki S, Michel JL, Jan D, Goulet O, Ricour C, Nihoul-Fekete C. Source: European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery . [et Al] = Zeitschrift Fur Kinderchirurgie. 2002 June; 12(3): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12101500&dopt=Abstract

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Inflammatory bowel disease (Crohn's disease) in a Spanish patient with pars plana exudates: report of a new case and review of the literature. Author(s): Gorrono-Echebarria MB, Albarran F, Marcos A, Alvarez-Mon M. Source: Ocular Immunology and Inflammation. 2002 March; 10(1): 65-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461705&dopt=Abstract

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Inflammatory signal transduction in Crohn's disease and novel therapeutic approaches. Author(s): van Montfrans C, Peppelenbosch M, te Velde AA, van Deventer S. Source: Biochemical Pharmacology. 2002 September; 64(5-6): 789-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213571&dopt=Abstract

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Infliximab (REMICADE) therapy in the treatment of pediatric Crohn's disease. Author(s): Baldassano R, Braegger CP, Escher JC, DeWoody K, Hendricks DF, Keenan GF, Winter HS. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 833-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738464&dopt=Abstract

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Infliximab as first-line therapy for Crohn's disease is premature. Author(s): Greenberg GR. Source: Inflammatory Bowel Diseases. 2002 January; 8(1): 60-2; Discussion 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837941&dopt=Abstract

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Infliximab as first-line therapy for severe Crohn's disease? Author(s): Cohen RD. Source: Inflammatory Bowel Diseases. 2002 January; 8(1): 58-9; Discussion 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837940&dopt=Abstract

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Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Author(s): Van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, van Montfrans C, Hommes DW, Peppelenbosch MP, van Deventer SJ. Source: Gastroenterology. 2003 June; 124(7): 1774-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806611&dopt=Abstract

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Infliximab decreases resource use among patients with Crohn's disease. Author(s): Rubenstein JH, Chong RY, Cohen RD. Source: Journal of Clinical Gastroenterology. 2002 August; 35(2): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172361&dopt=Abstract

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Infliximab does not interfere with insulin secretion, insulin resistance and production of GAD and islet cell antibodies in patients with Crohn's disease. Author(s): Gentile S, Guarino G, Bizzarro A, De Bellis A, Torella R. Source: Diabetes, Obesity & Metabolism. 2002 July; 4(4): 276-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099977&dopt=Abstract

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Infliximab for Crohn's disease in clinical practice: the experience of a single center in romania. Author(s): Gheorghe L, Gheorghe C, Badea M, Vadan R, Parvulescu I, Toader C, Tugui L, Papuc O, Ionescu R, Preda C, Calin I, Diculescu M. Source: Rom J Gastroenterol. 2003 March; 12(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673373&dopt=Abstract

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Infliximab for the treatment of Crohn's disease: efficacy, safety and pharmacoeconomics. Author(s): Feagan BG, Enns R, Fedorak RN, Panaccione R, Pare P, Steinhart AH, Wild G. Source: Can J Clin Pharmacol. 2001 Winter; 8(4): 188-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743591&dopt=Abstract

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Infliximab improves quality of life in patients with Crohn's disease. Author(s): Lichtenstein GR, Bala M, Han C, DeWoody K, Schaible T. Source: Inflammatory Bowel Diseases. 2002 July; 8(4): 237-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131606&dopt=Abstract

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Infliximab in the treatment of Crohn's disease: a user's guide for clinicians. Author(s): Sandborn WJ, Hanauer SB. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 2962-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492177&dopt=Abstract

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Infliximab in treatment of Crohn's disease: the Milan experience. Author(s): Ardizzone S, Colombo E, Maconi G, Bollani S, Manzionna G, Petrone MC, Bianchi Porro G. Source: Dig Liver Dis. 2002 June; 34(6): 411-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132788&dopt=Abstract

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Infliximab retreatment in adults and children with Crohn's disease: risk factors for the development of delayed severe systemic reaction. Author(s): Kugathasan S, Levy MB, Saeian K, Vasilopoulos S, Kim JP, Prajapati D, Emmons J, Martinez A, Kelly KJ, Binion DG. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1408-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094858&dopt=Abstract

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Infliximab therapy in Crohn's disease: safety issues. Author(s): Hommes DW, van Deventer SJ. Source: The Netherlands Journal of Medicine. 2003 April; 61(4): 100-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852717&dopt=Abstract

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Infliximab treatment and prognostic factors for response in patients with Crohn's disease. Author(s): Mendoza JL, Garcia-Paredes J, Cruz Santamaria DM, Lana R, Ramirez Fernandez E, Rodriguez Asteaga E, Diaz-Rubio M. Source: Rev Esp Enferm Dig. 2002 May; 94(5): 269-79. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474335&dopt=Abstract

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Infliximab treatment for Crohn's disease: one-year experience in a Dutch academic hospital. Author(s): Hommes DW, van de Heisteeg BH, van der Spek M, Bartelsman JF, van Deventer SJ. Source: Inflammatory Bowel Diseases. 2002 March; 8(2): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854604&dopt=Abstract

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Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease. Author(s): ten Hove T, van Montfrans C, Peppelenbosch MP, van Deventer SJ. Source: Gut. 2002 February; 50(2): 206-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788561&dopt=Abstract

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Infliximab treatment of an esophagobronchial fistula in a patient with extensive Crohn's disease of the esophagus. Author(s): Ho IK, Guarino DP, Pertsovskiy Y, Cerulli MA. Source: Journal of Clinical Gastroenterology. 2002 April; 34(4): 488-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907371&dopt=Abstract

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Infliximab treatment of Crohn's disease in children: it's time to not go retro(spective). Author(s): Hyams JS. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 5-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526928&dopt=Abstract

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Infliximab: an updated review of its use in Crohn's disease and rheumatoid arthritis. Author(s): Keating GM, Perry CM. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2002; 16(2): 111-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985485&dopt=Abstract

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Influence of experience on laparoscopic ileocolic resection for Crohn's disease. Author(s): Evans J, Poritz L, MacRae H. Source: Diseases of the Colon and Rectum. 2002 December; 45(12): 1595-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473881&dopt=Abstract

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Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease. Author(s): Hommes D, van den Blink B, Plasse T, Bartelsman J, Xu C, Macpherson B, Tytgat G, Peppelenbosch M, Van Deventer S. Source: Gastroenterology. 2002 January; 122(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781274&dopt=Abstract

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Initial presentation of Crohn's disease in pregnancy: report of a case. Author(s): Goettler CE, Stellato TA. Source: Diseases of the Colon and Rectum. 2003 March; 46(3): 406-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626919&dopt=Abstract

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Initial therapy for mild to moderate Crohn's disease: mesalamine or budesonide? Author(s): Feagan BG, Sandborn WJ. Source: Reviews in Gastroenterological Disorders. 2002; 2 Suppl 2: S9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478239&dopt=Abstract

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Interaction between azathioprine and aminosalicylates: an in vivo study in patients with Crohn's disease. Author(s): Dewit O, Vanheuverzwyn R, Desager JP, Horsmans Y. Source: Alimentary Pharmacology & Therapeutics. 2002 January; 16(1): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856081&dopt=Abstract

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Intermittent small bowel obstruction by jejunal enteroliths in a patient with a Crohn's disease stricture. Author(s): Bruni R, Chirco L, Lemeni AR, Petrocca S. Source: Chir Ital. 2002 November-December; 54(6): 903-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613344&dopt=Abstract

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Intestinal permeability in Crohn's disease patients and their first degree relatives. Author(s): Secondulfo M, de Magistris L, Fiandra R, Caserta L, Belletta M, Tartaglione MT, Riegler G, Biagi F, Corazza GR, Carratu R. Source: Dig Liver Dis. 2001 November; 33(8): 680-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785714&dopt=Abstract

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Intestinal permeability in patients with Crohn's disease and their relatives. Author(s): Hollander D. Source: Dig Liver Dis. 2001 November; 33(8): 649-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785707&dopt=Abstract

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Intra-abdominal abscess in Crohn's disease: a case report. Author(s): Fuengfoo P, Wisutthipat S, Vassanasiri W, Punyarit P. Source: J Med Assoc Thai. 2002 March; 85(3): 376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117029&dopt=Abstract

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Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Author(s): Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Source: Gastroenterology. 2003 April; 124(4): 917-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671888&dopt=Abstract

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Is Crohn's disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis, and Johne's disease. Author(s): Greenstein RJ. Source: The Lancet Infectious Diseases. 2003 August; 3(8): 507-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901893&dopt=Abstract

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Isolation of peptides useful for differential diagnosis of Crohn's disease and ulcerative colitis. Author(s): Saito H, Fukuda Y, Katsuragi K, Tanaka M, Satomi M, Shimoyama T, Saito T, Tachikawa T. Source: Gut. 2003 April; 52(4): 535-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631665&dopt=Abstract

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Jaundice caused by a pancreatic mass: an exceptional presentation of Crohn's disease. Author(s): Reynaert H, Peters O, Van der Auwera J, Vanstapel MJ, Urbain D. Source: Journal of Clinical Gastroenterology. 2001 March; 32(3): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246358&dopt=Abstract

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Kallikrein-kinin system activation in Crohn's disease: differences in intestinal and systemic markers. Author(s): Devani M, Cugno M, Vecchi M, Ferrero S, Di Berardino F, Avesani EC, de Franchis R, Colman RW. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2026-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190172&dopt=Abstract

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Kaposi's sarcoma and cytomegaloviral ileocolitis complicating long-standing Crohn's disease in an HIV-negative patient. Author(s): Cohen RL, Tepper RE, Urmacher C, Katz S. Source: The American Journal of Gastroenterology. 2001 October; 96(10): 3028-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693345&dopt=Abstract

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Keeping the M in mind: recombinant human GMCSF and Crohn's disease. Author(s): Bickston SJ. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 132. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769449&dopt=Abstract

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Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study. Author(s): Reif S, Lavy A, Keter D, Fich A, Eliakim R, Halak A, Broide E, Niv Y, Ron Y, Patz J, Odes S, Villa Y, Gilat T. Source: The American Journal of Gastroenterology. 2000 February; 95(2): 474-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10685753&dopt=Abstract

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Lack of association of ankylosing spondylitis with the most common NOD2 susceptibility alleles to Crohn's disease. Author(s): Ferreiros-Vidal I, Amarelo J, Barros F, Carracedo A, Gomez-Reino JJ, Gonzalez A. Source: The Journal of Rheumatology. 2003 January; 30(1): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508397&dopt=Abstract

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Lack of common NOD2 variants in Japanese patients with Crohn's disease. Author(s): Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y, Inohara N, Nunez G, Kishi Y, Koike Y, Shimosegawa T, Shimoyama T, Hibi T. Source: Gastroenterology. 2002 July; 123(1): 86-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105836&dopt=Abstract

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Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. North American Azathioprine Study Group. Author(s): Sandborn WJ, Tremaine WJ, Wolf DC, Targan SR, Sninsky CA, Sutherland LR, Hanauer SB, McDonald JW, Feagan BG, Fedorak RN, Isaacs KL, Pike MG, Mays DC, Lipsky JJ, Gordon S, Kleoudis CS, Murdock RH Jr. Source: Gastroenterology. 1999 September; 117(3): 527-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464128&dopt=Abstract

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Lack of effect of intravenous azathioprine on time to respond for steroid treated Crohn's disease. Author(s): Carter MJ, Lobo AJ. Source: Gut. 2001 March; 48(3): 295-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171815&dopt=Abstract

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Lack of efficacy of ridogrel, a thromboxane synthase inhibitor, in a placebocontrolled, double-blind, multi-centre clinical trial in active Crohn's disease. Author(s): Carty E, Rampton DS, Schneider H, Rutgeerts P, Wright JP. Source: Alimentary Pharmacology & Therapeutics. 2001 September; 15(9): 1323-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552902&dopt=Abstract

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Lack of support for a common etiology in Johne's disease of animals and Crohn's disease in humans. Author(s): Van Kruiningen HJ. Source: Inflammatory Bowel Diseases. 1999 August; 5(3): 183-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453375&dopt=Abstract

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Lacrimal gland inflammation as the presenting sign of Crohn's disease. Author(s): Hwang IP, Jordan DR, Acharya V. Source: Can J Ophthalmol. 2001 June; 36(4): 212-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11428531&dopt=Abstract

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Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis. Author(s): von Tirpitz C, Kohn C, Steinkamp M, Geerling I, Maier V, Moller P, Adler G, Reinshagen M. Source: Journal of Clinical Gastroenterology. 2002 January; 34(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743245&dopt=Abstract

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Laparoscopic appendectomy for Crohn's disease of the appendix presenting as acute appendicitis. Author(s): Zager JS, Gusani NJ, Derubertis BG, Shaw JP, Kaufman JP, DeNoto G. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2001 August; 11(4): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569518&dopt=Abstract

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Laparoscopic colectomy in diverticular and Crohn's disease. Author(s): Wexner SD, Moscovitz ID. Source: The Surgical Clinics of North America. 2000 August; 80(4): 1299-319. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987037&dopt=Abstract

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Laparoscopic ileocecal resection for Crohn's disease associated with intestinal stenosis and ileorectal fistula. Author(s): Watanabe M, Ohgami M, Teramoto T, Hibi T, Kitajima M. Source: Surgery Today. 1999; 29(5): 446-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10333417&dopt=Abstract

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Laparoscopic ileocecal resection in Crohn's disease: a case-matched comparison with open resection. Author(s): Benoist S, Panis Y, Beaufour A, Bouhnik Y, Matuchansky C, Valleur P. Source: Surgical Endoscopy. 2003 May; 17(5): 814-8. Epub 2003 January 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584603&dopt=Abstract

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Laparoscopic management of complex Crohn's disease. Author(s): Seymour NE, Kavic SM. Source: Jsls. 2003 April-June; 7(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856841&dopt=Abstract

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Laparoscopic surgery for Crohn's disease: reasons for conversion. Author(s): Schmidt CM, Talamini MA, Kaufman HS, Lilliemoe KD, Learn P, Bayless T. Source: Annals of Surgery. 2001 June; 233(6): 733-9. Erratum In: Ann Surg 2001 August; 234(2): Following Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11371731&dopt=Abstract

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Laparoscopic surgery for Crohn's disease?--a conditional yes. Author(s): Breen EM, Ashley SW. Source: Inflammatory Bowel Diseases. 2000 February; 6(1): 43-5; Discussion 46-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701149&dopt=Abstract

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Laparoscopic surgery for recurrent Crohn's disease. Author(s): Hasegawa H, Watanabe M, Nishibori H, Okabayashi K, Hibi T, Kitajima M. Source: The British Journal of Surgery. 2003 August; 90(8): 970-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905550&dopt=Abstract

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Laparoscopic surgery in Crohn's disease. Author(s): Aleali M, Milsom JW. Source: The Surgical Clinics of North America. 2001 February; 81(1): 217-30, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218166&dopt=Abstract

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Laparoscopic versus open bowel resection for Crohn's disease. Author(s): Tabet J, Hong D, Kim CW, Wong J, Goodacre R, Anvari M. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 April; 15(4): 237-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331925&dopt=Abstract

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Laparoscopically assisted hemicolectomy for Crohn's disease: are we still getting better? Author(s): Hamel CT, Pikarsky AJ, Wexner SD. Source: The American Surgeon. 2002 January; 68(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467325&dopt=Abstract

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Laparoscopically assisted ileocolectomy for Crohn's disease through a pfannenstiel incision. Author(s): Greene AK, Michetti P, Peppercorn MA, Hodin RA. Source: American Journal of Surgery. 2000 September; 180(3): 238-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084138&dopt=Abstract

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Laparoscopically assisted intestinal resection in 88 patients with Crohn's disease. Author(s): Canin-Endres J, Salky B, Gattorno F, Edye M. Source: Surgical Endoscopy. 1999 June; 13(6): 595-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10347299&dopt=Abstract

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Laparoscopic-assisted bowel resection offers advantages over open surgery for treatment of segmental Crohn's disease in children. Author(s): von Allmen D, Markowitz JE, York A, Mamula P, Shepanski M, Baldassano R. Source: Journal of Pediatric Surgery. 2003 June; 38(6): 963-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778403&dopt=Abstract

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Laparoscopic-assisted surgery for Crohn's disease: reduced surgical stress following ileocolectomy. Author(s): Kishi D, Nezu R, Ito T, Taniguchi E, Momiyama T, Obunai S, Ohashi S, Matsuda H. Source: Surgery Today. 2000; 30(3): 219-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10752772&dopt=Abstract

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Laparoscopic-assisted vs. open ileocolic resection for Crohn's disease. A comparative study. Author(s): Bemelman WA, Slors JF, Dunker MS, van Hogezand RA, van Deventer SJ, Ringers J, Griffioen G, Gouma DJ. Source: Surgical Endoscopy. 2000 August; 14(8): 721-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10954817&dopt=Abstract

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Laryngeal and other otolaryngologic manifestations of Crohn's disease. Author(s): Yang J, Maronian N, Reyes V, Waugh P, Brentnall T, Hillel A. Source: Journal of Voice : Official Journal of the Voice Foundation. 2002 June; 16(2): 27882. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150381&dopt=Abstract

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Lessons from genetically engineered animal models XI. Novel mouse models to study pathogenic mechanisms of Crohn's disease. Author(s): Pizarro TT, Arseneau KO, Cominelli F. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2000 May; 278(5): G665-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801257&dopt=Abstract

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Lessons to be learned from the NOD2 gene in Crohn's disease. Author(s): Hugot JP, Zouali H, Lesage S. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 593-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840668&dopt=Abstract

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Linkage heterogeneity for the IBD1 locus in Crohn's disease pedigrees by disease onset and severity. Author(s): Brant SR, Panhuysen CI, Bailey-Wilson JE, Rohal PM, Lee S, Mann J, Ravenhill G, Kirschner BS, Hanauer SB, Cho JH, Bayless TM. Source: Gastroenterology. 2000 December; 119(6): 1483-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113069&dopt=Abstract

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Linkage of Crohn's disease to the major histocompatibility complex region is detected by multiple non-parametric analyses. Author(s): Yang H, Plevy SE, Taylor K, Tyan D, Fischel-Ghodsian N, McElree C, Targan SR, Rotter JI. Source: Gut. 1999 April; 44(4): 519-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10075959&dopt=Abstract

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Liquid diets for Crohn's disease. Author(s): O'Sullivan M, O'Morain C. Source: Gut. 2001 June; 48(6): 757. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358889&dopt=Abstract

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Liquid pancreatic enzyme therapy for a patient with short bowel syndrome and chronic pancreatitis in a complicated case of Crohn's disease. Author(s): Hardt PD, Helfrich C, Klauke T, Klor HU. Source: European Journal of Medical Research. 1999 August 25; 4(8): 345-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10471547&dopt=Abstract

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Lithogenic risk factors for renal stones in patients with Crohn's disease. Author(s): Buno Soto A, Torres Jimenez R, Olveira A, Fernandez-Blanco Herraiz I, Montero Garcia A, Mateos Anton F. Source: Arch Esp Urol. 2001 April; 54(3): 282-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11432047&dopt=Abstract

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Little benefit from mesalazine taken prophylactically after surgery for Crohn's disease. Author(s): Rutgeerts P. Source: Gut. 2001 April; 48(4): 452-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247886&dopt=Abstract

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Localized giant pseudopolyposis in Crohn's disease. Author(s): Ryu CB, Kwon KW, Kim JO, Lee MS, Shim CS, Kim BS. Source: Gastrointestinal Endoscopy. 2002 June; 55(7): 914. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024154&dopt=Abstract

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Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy. Author(s): Allez M, Lemann M, Bonnet J, Cattan P, Jian R, Modigliani R. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 947-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003431&dopt=Abstract

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Longitudinal analysis of plasma cytomegalovirus DNA in a child with Crohn's disease and cytomegalovirus gastroenteritis. Author(s): Udall JN Jr, Hempe JM, Schmidt-Sommerfeld E, Scheer WD, Mannick E, Blecker U, Correa H. Source: Journal of Pediatric Gastroenterology and Nutrition. 1999 May; 28(5): 502-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10328126&dopt=Abstract

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Longitudinal study of bone mineral density in patients with Crohn's disease. Author(s): de Jong DJ, Mannaerts L, van Rossum LG, Corstens FH, Naber AH. Source: Digestive Diseases and Sciences. 2003 July; 48(7): 1355-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870795&dopt=Abstract

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Long-term cyclosporine for resistant Crohn's disease. Author(s): Lavy A. Source: Journal of Clinical Gastroenterology. 1999 April; 28(3): 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192614&dopt=Abstract

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Long-term evolution of disease behavior of Crohn's disease. Author(s): Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, Gendre JP. Source: Inflammatory Bowel Diseases. 2002 July; 8(4): 244-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131607&dopt=Abstract

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Long-term fracture risk in patients with Crohn's disease: a population-based study in Olmsted County, Minnesota. Author(s): Loftus EV Jr, Crowson CS, Sandborn WJ, Tremaine WJ, O'Fallon WM, Melton LJ 3rd. Source: Gastroenterology. 2002 August; 123(2): 468-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145800&dopt=Abstract

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Long-term outcome of non-surgical strictureplasty using metallic stents for intestinal strictures in Crohn's disease. Author(s): Matsuhashi N, Nakajima A, Suzuki A, Yazaki Y, Takazoe M. Source: Gastrointestinal Endoscopy. 2000 March; 51(3): 343-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699786&dopt=Abstract

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Long-term outcome of surgical management for diffuse jejunoileal Crohn's disease. Author(s): Yamamoto T, Allan RN, Keighley MR. Source: Surgery. 2001 January; 129(1): 96-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150039&dopt=Abstract

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Long-term results and multivariate analysis of prognostic factors in 138 consecutive patients operated on for Crohn's disease using "bowel-sparing" techniques. Author(s): Cristaldi M, Sampietro GM, Danelli PG, Bollani S, Bianchi Porro G, Taschieri AM. Source: American Journal of Surgery. 2000 April; 179(4): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875983&dopt=Abstract

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Long-term results of ileal pouch-anal anastomosis for colorectal Crohn's disease. Author(s): Regimbeau JM, Panis Y, Pocard M, Bouhnik Y, Lavergne-Slove A, Rufat P, Matuchansky C, Valleur P. Source: Diseases of the Colon and Rectum. 2001 June; 44(6): 769-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391134&dopt=Abstract

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Long-term results of ileal pouch-anal anastomosis in Crohn's disease. Author(s): de Oca J, Sanchez-Santos R, Rague JM, Biondo S, Pares D, Osorio A, del Rio C, Jaurrieta E. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792222&dopt=Abstract

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Long-term results of seton drainage on complex anal fistulae in patients with Crohn's disease. Author(s): Takesue Y, Ohge H, Yokoyama T, Murakami Y, Imamura Y, Sueda T. Source: Journal of Gastroenterology. 2002; 37(11): 912-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483246&dopt=Abstract

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Long-term results of stapled and hand-sewn anastomoses in patients with Crohn's disease. Author(s): Ikeuchi H, Kusunoki M, Yamamura T. Source: Digestive Surgery. 2000; 17(5): 493-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11124554&dopt=Abstract

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Long-term results of strictureplasty for ileocolonic anastomotic recurrence in Crohn's disease. Author(s): Yamamoto T, Keighley MR. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 1999 September-October; 3(5): 555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10482715&dopt=Abstract

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Long-term results of strictureplasty without synchronous resection for jejunoileal Crohn's disease. Author(s): Yamamoto T, Keighley MR. Source: Scandinavian Journal of Gastroenterology. 1999 February; 34(2): 180-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192197&dopt=Abstract

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Long-term tacrolimus: a promising therapeutic approach for Crohn's disease. Author(s): Ierardi E, Principi M, Francavilla R, Pisani A, Rendina M, Panella C, Francavilla A. Source: Transplantation Proceedings. 2001 May; 33(3): 2107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377467&dopt=Abstract

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Long-term treatment of Crohn's disease with methotrexate, or, why's a nice drug like you still a wannabe in the treatment of inflammatory bowel disease? Author(s): Kozarek RA. Source: The American Journal of Gastroenterology. 2000 July; 95(7): 1619-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10925959&dopt=Abstract

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Looking for Mycobacterium paratuberculosis DNA by polymerase chain reaction (PCR) in orofacial granulomatosis (OFG) and oral Crohn's disease tissue in an Irish population. Author(s): Gibson J, Riggio M, McCreary C, Lennon A, Toner M. Source: Ir Med J. 2000 October; 93(7): 218. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142959&dopt=Abstract

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Low back pain, sacroiliitis, and the relationship with HLA-B27 in Crohn's disease. Author(s): Steer S, Jones H, Hibbert J, Kondeatis E, Vaughan R, Sanderson J, Gibson T. Source: The Journal of Rheumatology. 2003 March; 30(3): 518-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610811&dopt=Abstract

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Low ileal interleukin 10 concentrations are predictive of endoscopic recurrence in patients with Crohn's disease. Author(s): Meresse B, Rutgeerts P, Malchow H, Dubucquoi S, Dessaint JP, Cohard M, Colombel JF, Desreumaux P. Source: Gut. 2002 January; 50(1): 25-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772962&dopt=Abstract

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Low mortality in ulcerative colitis and Crohn's disease in three regional centers in England. Author(s): Farrokhyar F, Swarbrick ET, Grace RH, Hellier MD, Gent AE, Irvine EJ. Source: The American Journal of Gastroenterology. 2001 February; 96(2): 501-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232697&dopt=Abstract

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Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease? Author(s): Schoon EJ, Muller MC, Vermeer C, Schurgers LJ, Brummer RJ, Stockbrugger RW. Source: Gut. 2001 April; 48(4): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247890&dopt=Abstract

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Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group. Author(s): Ewe K, Bottger T, Buhr HJ, Ecker KW, Otto HF. Source: European Journal of Gastroenterology & Hepatology. 1999 March; 11(3): 277-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10333200&dopt=Abstract

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Lymph loss in the bowel and severe nutritional disturbances in Crohn's disease. Author(s): Baert D, Wulfrank D, Burvenich P, Lagae J. Source: Journal of Clinical Gastroenterology. 1999 October; 29(3): 277-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10509957&dopt=Abstract

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Lymphoedema and Crohn's disease. Author(s): Monk BE, Mortimer PS. Source: Journal of the Royal Society of Medicine. 1999 March; 92(3): 136-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10396260&dopt=Abstract

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Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn's disease. Author(s): Kanai T, Watanabe M, Okazawa A, Sato T, Yamazaki M, Okamoto S, Ishii H, Totsuka T, Iiyama R, Okamoto R, Ikeda M, Kurimoto M, Takeda K, Akira S, Hibi T. Source: Gastroenterology. 2001 October; 121(4): 875-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606501&dopt=Abstract

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Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease. Author(s): Van Assche G, Vanbeckevoort D, Bielen D, Coremans G, Aerden I, Noman M, D'Hoore A, Penninckx F, Marchal G, Cornillie F, Rutgeerts P. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 332-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591051&dopt=Abstract

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Magnetic resonance spectroscopy: a new test for differentiating ulcerative colitis from Crohn's disease? Author(s): Mandal A, Mayberry J. Source: The American Journal of Gastroenterology. 2001 February; 96(2): 271-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232662&dopt=Abstract

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Maintenance infliximab for Crohn's disease. Author(s): Cottone M, Orlando A, Casa A, Oliva L. Source: Lancet. 2002 November 16; 360(9345): 1602; Author Reply 1602-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443622&dopt=Abstract

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Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Author(s): Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P; ACCENT I Study Group. Source: Lancet. 2002 May 4; 359(9317): 1541-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047962&dopt=Abstract

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Maintenance infliximab therapy in patients with Crohn's disease: how long, how much, how frequent? Author(s): Cuffari C, Lichtenstein GR. Source: Gastroenterology. 2003 June; 124(7): 1988-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806638&dopt=Abstract

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Maintenance of Crohn's disease over 12 months: fixed versus flexible dosing regimen using budesonide controlled ileal release capsules. Author(s): Green JR, Lobo AJ, Giaffer M, Travis S, Watkins HC; Freedom Investigator Group. Source: Alimentary Pharmacology & Therapeutics. 2001 September; 15(9): 1331-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552903&dopt=Abstract

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Maintenance therapy in Crohn's disease. Author(s): Steinhart H. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 September; 14 Suppl C: 23C-28C. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023557&dopt=Abstract

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Management of an ileocolic anastomotic stricture using polyvinyl over-the-guidewire dilators in Crohn's disease. Author(s): Morini S, Hassan C, Cerro P, Lorenzetti R. Source: Gastrointestinal Endoscopy. 2001 March; 53(3): 384-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231412&dopt=Abstract

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Management of Crohn's disease in adults. Author(s): Hanauer SB, Sandborn W; Practice Parameters Committee of the American College of Gastroenterology. Source: The American Journal of Gastroenterology. 2001 March; 96(3): 635-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280528&dopt=Abstract

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Management of Crohn's disease--a practical approach. Author(s): Knutson D, Greenberg G, Cronau H. Source: American Family Physician. 2003 August 15; 68(4): 707-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952387&dopt=Abstract

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Management of fistulas in Crohn's disease. Author(s): Ikeuchi H, Shoji Y, Yamamura T. Source: Digestive Surgery. 2002; 19(1): 36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961353&dopt=Abstract

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Management of fistulas in patients with Crohn's disease: antibiotic to antibody. Author(s): Pare P. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 November; 15(11): 751-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11727005&dopt=Abstract

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Management of growth retardation in the young patient with Crohn's disease. Author(s): Ballinger A. Source: Expert Opinion on Pharmacotherapy. 2002 January; 3(1): 1-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772328&dopt=Abstract

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Management of internal fistulas in Crohn's disease. Author(s): Levy C, Tremaine WJ. Source: Inflammatory Bowel Diseases. 2002 March; 8(2): 106-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854609&dopt=Abstract

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Managing Crohn's disease and ulcerative colitis. Author(s): Evans S, Ciclitira PJ. Source: Practitioner. 1999 April; 243(1597): 307-14. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10492973&dopt=Abstract

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Mannan-binding lectin (MBL) gene polymorphisms in ulcerative colitis and Crohn's disease. Author(s): Rector A, Lemey P, Laffut W, Keyaerts E, Struyf F, Wollants E, Vermeire S, Rutgeerts P, Van Ranst M. Source: Genes and Immunity. 2001 October; 2(6): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11607788&dopt=Abstract

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Measles is more prevalent in Crohn's disease patients. A multicentre Israeli study. Author(s): Lavy A, Broide E, Reif S, Keter D, Niv Y, Odes S, Eliakim R, Halak A, Ron Y, Patz J, Fich A, Villa Y, Arber N, Gilat T. Source: Dig Liver Dis. 2001 August-September; 33(6): 472-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572573&dopt=Abstract

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Measles virus and Crohn's disease: a critical appraisal of the current literature. Author(s): Robertson DJ, Sandler RS. Source: Inflammatory Bowel Diseases. 2001 February; 7(1): 51-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233661&dopt=Abstract

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Measles, month of birth, and Crohn's disease. Author(s): Haslam N, Mayberry JF, Hawthorne AB, Newcombe RG, Holmes GK, Probert CS. Source: Gut. 2000 December; 47(6): 801-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076878&dopt=Abstract

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Mechanisms of intestinal failure in Crohn's disease. Author(s): Agwunobi AO, Carlson GL, Anderson ID, Irving MH, Scott NA. Source: Diseases of the Colon and Rectum. 2001 December; 44(12): 1834-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742170&dopt=Abstract

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Meckel's diverticulum in Crohn's disease. Author(s): Freeman HJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 May; 15(5): 308-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381298&dopt=Abstract

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Medical management of major internal fistulae in Crohn's disease. Author(s): D'Haens G. Source: Inflammatory Bowel Diseases. 2000 August; 6(3): 244-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961596&dopt=Abstract

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Medical options for treating Crohn's disease in adults: focus on antitumor necrosis factor-alpha chimeric monoclonal antibody. Author(s): Wall GC, Heyneman C, Pfanner TP. Source: Pharmacotherapy. 1999 October; 19(10): 1138-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512063&dopt=Abstract

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Medical therapy for Crohn's disease: the state of the art. Author(s): Stein RB, Lichtenstein GR. Source: The Surgical Clinics of North America. 2001 February; 81(1): 71-101, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218170&dopt=Abstract

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Medical therapy of steroid-resistant Crohn's disease. Author(s): Sands BE. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 September; 14 Suppl C: 33C-37C. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023559&dopt=Abstract

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Medical treatment of Crohn's disease. Author(s): Harrison J, Hanauer SB. Source: Gastroenterology Clinics of North America. 2002 March; 31(1): 167-84, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122730&dopt=Abstract

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Melatonin triggers Crohn's disease symptoms. Author(s): Calvo JR, Guerrero JM, Osuna C, Molinero P, Carrillo-Vico A. Source: Journal of Pineal Research. 2002 May; 32(4): 277-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982800&dopt=Abstract

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Mesalamine and relapse prevention in Crohn's disease. Author(s): Cottone M, Camma C. Source: Gastroenterology. 2000 August; 119(2): 597. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10960274&dopt=Abstract

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Mesalamine maintenance therapy for Crohn's disease. Author(s): Feagan BG, McDonald JW. Source: Gastroenterology. 2001 February; 120(2): 585-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11271451&dopt=Abstract

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Mesenteric arterial thrombosis as a complication of Crohn's disease. Author(s): Sanghavi P, Paramesh A, Dwivedi A, Markova T, Phan T. Source: Digestive Diseases and Sciences. 2001 November; 46(11): 2344-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713933&dopt=Abstract

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Metastatic Crohn's disease involving the genitalia. Author(s): Poon KS, Gilks CB, Masterson JS. Source: The Journal of Urology. 2002 June; 167(6): 2541-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992084&dopt=Abstract

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Metastatic Crohn's disease of the forehead. Author(s): Biancone L, Geboes K, Spagnoli LG, Del Vecchio Blanco G, Monteleone I, Vavassori P, Palmieri G, Chimenti S, Pallone F. Source: Inflammatory Bowel Diseases. 2002 March; 8(2): 101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854608&dopt=Abstract

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Metastatic Crohn's disease: case report of an unusual variant and review of the literature. Author(s): Guest GD, Fink RL. Source: Diseases of the Colon and Rectum. 2000 December; 43(12): 1764-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156465&dopt=Abstract

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Methotrexate and maintenance of remission in Crohn's disease. Author(s): Fishman M. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 July; 15(7): 428. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11493943&dopt=Abstract

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Methotrexate for induction of remission in refractory Crohn's disease. Author(s): Alfadhli AA, McDonald JW, Feagan BG. Source: Cochrane Database Syst Rev. 2003; (1): Cd003459. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535475&dopt=Abstract

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Methotrexate for the maintenance of remission in Crohn's disease. Author(s): Yang YX, Lichtenstein GR. Source: Gastroenterology. 2001 May; 120(6): 1553-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313329&dopt=Abstract

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Methotrexate in Crohn's disease. Author(s): Rampton DS. Source: Gut. 2001 June; 48(6): 790-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358896&dopt=Abstract

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Methotrexate: a useful alternative in Crohn's disease? Author(s): Hawthorne AB. Source: Gut. 2001 July; 49(1): 9-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413103&dopt=Abstract

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Metronidazole plus ciprofloxacin therapy for active Crohn's disease. Author(s): Ishikawa T, Okamura S, Oshimoto H, Kobayashi R, Mori M. Source: Intern Med. 2003 April; 42(4): 318-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729319&dopt=Abstract

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MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis. Author(s): Glas J, Martin K, Brunnler G, Kopp R, Folwaczny C, Weiss EH, Albert ED. Source: Tissue Antigens. 2001 October; 58(4): 243-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782275&dopt=Abstract

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Minilaparotomy approach to terminal ileal Crohn's disease. Author(s): Nakagoe T, Sawai T, Tsuji T, Jibiki MA, Nanashima A, Yamaguchi H, Yasutake T, Ayabe H. Source: World Journal of Surgery. 2002 June; 26(6): 721-5. Epub 2002 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12053226&dopt=Abstract

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Molecular genetics and Crohn's disease. Author(s): Church JM. Source: The Surgical Clinics of North America. 2001 February; 81(1): 31-8, Vii-Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218168&dopt=Abstract

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Molecular therapies in Crohn's disease: coming of age. Author(s): Schreiber S. Source: International Journal of Colorectal Disease. 2002 September; 17(5): 285-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420727&dopt=Abstract

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Monoclonal antibody therapy for Crohn's disease. Author(s): Selby W. Source: Internal Medicine Journal. 2001 March; 31(2): 73-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480481&dopt=Abstract

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Monocyte/macrophage activation by normal bacteria and bacterial products: implications for altered epithelial function in Crohn's disease. Author(s): Zareie M, Singh PK, Irvine EJ, Sherman PM, McKay DM, Perdue MH. Source: American Journal of Pathology. 2001 March; 158(3): 1101-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238058&dopt=Abstract

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Monocytes or T cells in Crohn's disease: does IL-16 allow both to play at that game? Author(s): Schreiber S. Source: Gut. 2001 December; 49(6): 747-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709502&dopt=Abstract

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Mortality and causes of death in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark. Author(s): Jess T, Winther KV, Munkholm P, Langholz E, Binder V. Source: Gastroenterology. 2002 June; 122(7): 1808-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055588&dopt=Abstract

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MR imaging evaluation of the activity of Crohn's disease. Author(s): Koh DM, Miao Y, Chinn RJ, Amin Z, Zeegen R, Westaby D, Healy JC. Source: Ajr. American Journal of Roentgenology. 2001 December; 177(6): 1325-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717076&dopt=Abstract

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MR imaging of Crohn's disease: what is the attraction? Author(s): Ott DJ. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 211-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526963&dopt=Abstract

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MRI evaluation of Crohn's disease of the small and large bowel with the use of negative superparamagnetic oral contrast agents. Author(s): Maccioni F, Viscido A, Marini M, Caprilli R. Source: Abdominal Imaging. 2002 July-August; 27(4): 384-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066236&dopt=Abstract

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Mucin gene expression in intestinal epithelial cells in Crohn's disease. Author(s): Buisine MP, Desreumaux P, Leteurtre E, Copin MC, Colombel JF, Porchet N, Aubert JP. Source: Gut. 2001 October; 49(4): 544-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559653&dopt=Abstract

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Multiplanar spiral CT enterography in patients with Crohn's disease using a negative oral contrast material: initial results of a noninvasive imaging approach. Author(s): Reittner P, Goritschnig T, Petritsch W, Doerfler O, Preidler KW, Hinterleitner T, Szolar DH. Source: European Radiology. 2002 September; 12(9): 2253-7. Epub 2002 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195478&dopt=Abstract

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Multiple accumulation of Vdelta2+ gammadelta T-cell clonotypes in intestinal mucosa from patients with Crohn's disease. Author(s): Kanazawa H, Ishiguro Y, Munakata A, Morita T. Source: Digestive Diseases and Sciences. 2001 February; 46(2): 410-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281192&dopt=Abstract

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Multiple ostomy complications in a patient with Crohn's disease: a case study. Author(s): Parascandolo ME. Source: Journal of Wound, Ostomy, and Continence Nursing : Official Publication of the Wound, Ostomy and Continence Nurses Society / Wocn. 2001 September; 28(5): 236-41; Discussion 241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11557927&dopt=Abstract

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Multiple pyogenic liver abscesses associated with occult appendicitis and possible Crohn's disease. Author(s): Usdan LS, Massinople C. Source: Tenn Med. 2002 November; 95(11): 463-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436861&dopt=Abstract

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Multiple strictures in jejunal Crohn's disease: push enteroscopy dilation. Author(s): Perez-Cuadrado E, Molina Perez E. Source: Endoscopy. 2001 February; 33(2): 194. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272226&dopt=Abstract

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Musculoskeletal complications of Crohn's disease: the role of computed tomography in diagnosis and patient management. Author(s): Brenner HI, Fishman EK, Harris ML, Bayless TM. Source: Orthopedics. 2000 November; 23(11): 1181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11103962&dopt=Abstract

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Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. Author(s): Abreu MT, Taylor KD, Lin YC, Hang T, Gaiennie J, Landers CJ, Vasiliauskas EA, Kam LY, Rojany M, Papadakis KA, Rotter JI, Targan SR, Yang H. Source: Gastroenterology. 2002 September; 123(3): 679-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198692&dopt=Abstract

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Mycobacterium avium subspecies paratuberculosis as a cause of Crohn's disease. Author(s): Grimes DS. Source: Gut. 2003 January; 52(1): 155. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477784&dopt=Abstract

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Nasal septal perforation: a rare extraintestinal manifestation of Crohn's disease. Author(s): Kriskovich MD, Kelly SM, Jackson WD. Source: Ear, Nose, & Throat Journal. 2000 July; 79(7): 520-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10935304&dopt=Abstract

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Natalizumab for active Crohn's disease. Author(s): Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, Vyhnalek P, Zadorova Z, Palmer T, Donoghue S; Natalizumab Pan-European Study Group. Source: The New England Journal of Medicine. 2003 January 2; 348(1): 24-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510039&dopt=Abstract

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Natalizumab for active Crohn's disease. Author(s): Lew EA, Stoffel EM. Source: The New England Journal of Medicine. 2003 April 17; 348(16): 1599; Author Reply 1599. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700383&dopt=Abstract

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Natalizumab: a new hope for Crohn's disease? Author(s): Napier J, Wong RK. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1197-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830820&dopt=Abstract

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Necrobiotic nodules: a rare pulmonary manifestion of Crohn's disease. Author(s): Sanjeevi A, Roy HK. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 941-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738489&dopt=Abstract

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Necrotizing fasciitis in Crohn's disease. Author(s): Panter SJ, Bramble MG, Bell JR. Source: European Journal of Gastroenterology & Hepatology. 2001 April; 13(4): 429-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11338075&dopt=Abstract

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Negative association between smoking and anti-saccharomyces cerevisiae antibodies in Crohn's disease. Author(s): Van Kemseke C, Belaiche J, Steeman C, Louis E. Source: Acta Gastroenterol Belg. 2003 January-March; 66(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812142&dopt=Abstract

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Neoplasia of the tongue in a patient with Crohn's disease treated with azathioprine: case report. Author(s): Li AC, Warnakulasuriya S, Thompson RP. Source: European Journal of Gastroenterology & Hepatology. 2003 February; 15(2): 1857. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560764&dopt=Abstract

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Neurotransmitter coding of enteric neurones in the submucous plexus is changed in non-inflamed rectum of patients with Crohn's disease. Author(s): Schneider J, Jehle EC, Starlinger MJ, Neunlist M, Michel K, Hoppe S, Schemann M. Source: Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. 2001 June; 13(3): 255-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437988&dopt=Abstract

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New aspects of surgical therapy of recurrent Crohn's disease. Author(s): Kroesen AJ, Buhr HJ. Source: Yonsei Medical Journal. 2000 February; 41(1): 1-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10731912&dopt=Abstract

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New life in a sleeper: thalidomide and Crohn's disease. Author(s): Sands BE, Podolsky DK. Source: Gastroenterology. 1999 December; 117(6): 1485-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10579990&dopt=Abstract

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New targets for Crohn's disease. Author(s): Pestell K. Source: Trends in Pharmacological Sciences. 2001 July; 22(7): 342. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11431024&dopt=Abstract

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New therapeutic approaches to Crohn's disease. Author(s): Sartor RB. Source: The New England Journal of Medicine. 2000 June 1; 342(22): 1664-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833215&dopt=Abstract

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New therapy for orolaryngeal manifestations of Crohn's disease. Author(s): Ottaviani F, Schindler A, Capaccio P, Petrone M, Porro GB. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 January; 112(1): 37-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537056&dopt=Abstract

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NOD2 (CARD15), the first susceptibility gene for Crohn's disease. Author(s): McGovern DP, van Heel DA, Ahmad T, Jewell DP. Source: Gut. 2001 December; 49(6): 752-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709505&dopt=Abstract

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NOD2 insertion mutation in a Cretan Crohn's disease population. Author(s): Roussomoustakaki M, Koutroubakis I, Vardas EM, Dimoulios P, Kouroumalis EA, Baritaki S, Koutsoudakis G, Krambovitis E. Source: Gastroenterology. 2003 January; 124(1): 272-3; Author Reply 273-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512064&dopt=Abstract

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NOD2/CARD15 does not influence response to infliximab in Crohn's disease. Author(s): Vermeire S, Louis E, Rutgeerts P, De Vos M, Van Gossum A, Belaiche J, Pescatore P, Fiasse R, Pelckmans P, Vlietinck R, Merlin F, Zouali H, Thomas G, Colombel JF, Hugot JP; Belgian Group of Infliximab Expanded Access Program and Fondation Jean Dausset CEPH, Paris, France. Source: Gastroenterology. 2002 July; 123(1): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105838&dopt=Abstract

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NOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population. Author(s): Leong RW, Armuzzi A, Ahmad T, Wong ML, Tse P, Jewell DP, Sung JJ. Source: Alimentary Pharmacology & Therapeutics. 2003 June 15; 17(12): 1465-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823148&dopt=Abstract

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Noninfectious lung pathology in patients with Crohn's disease. Author(s): Casey MB, Tazelaar HD, Myers JL, Hunninghake GW, Kakar S, Kalra SX, Ashton R, Colby TV. Source: The American Journal of Surgical Pathology. 2003 February; 27(2): 213-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548168&dopt=Abstract

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Noninvasive assessment of Crohn's disease activity: a comparison of 18Ffluorodeoxyglucose positron emission tomography, hydromagnetic resonance imaging, and granulocyte scintigraphy with labeled antibodies. Author(s): Neurath MF, Vehling D, Schunk K, Holtmann M, Brockmann H, Helisch A, Orth T, Schreckenberger M, Galle PR, Bartenstein P. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 1978-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190164&dopt=Abstract

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Novel medical therapies for crohn's disease: is there room for growth? Author(s): Judge TA, Lichtenstein GR. Source: Gastroenterology. 2001 January; 120(1): 308-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208743&dopt=Abstract

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Nutrition and Crohn's disease. Author(s): Podolsky DK. Source: Journal of Gastroenterology. 2000; 35 Suppl 12: 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10779209&dopt=Abstract

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Nutrition and Crohn's disease: a case study in ambiguity. Author(s): Ooi CJ, Podolsky DK. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 January; 16(1): 76-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674246&dopt=Abstract

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Nutrition as primary therapy in pediatric Crohn's disease: fact or fantasy? Author(s): Ruemmele FM, Roy CC, Levy E, Seidman EG. Source: The Journal of Pediatrics. 2000 March; 136(3): 285-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10700682&dopt=Abstract

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Nutrition in Crohn's disease. Author(s): Philipsen-Geerling BJ, Brummer RJ. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2000 July; 3(4): 305-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929678&dopt=Abstract

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Nutrition in Crohn's disease. Author(s): Pullen M. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1999 March 24-30; 13(27): 48-52; Quiz 54-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10347483&dopt=Abstract

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Nutritional support for Crohn's disease. Author(s): Song HK, Buzby GP. Source: The Surgical Clinics of North America. 2001 February; 81(1): 103-15, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218158&dopt=Abstract

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Objectives and outcomes in the conventional treatment of pediatric Crohn's disease. Author(s): Buller HA. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 September; 33 Suppl 1: S11-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685970&dopt=Abstract

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Observer variation of diagnoses based on simple biopsy criteria differentiating among Crohn's disease, ulcerative colitis, and other forms of colitis. Author(s): Tanaka M, Masuda T, Yao T, Saito H, Kusumi T, Nagura H, Kudo H. Source: Journal of Gastroenterology and Hepatology. 2001 December; 16(12): 1368-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851834&dopt=Abstract

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Obstructing enterolith as presenting feature in Crohn's disease. Author(s): Shah SR, Bhaduri A, Desai DC, Abraham P, Joshi A. Source: Indian J Gastroenterol. 2003 January-February; 22(1): 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617449&dopt=Abstract

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Omentoplasty for persistent perineal sinus after proctectomy for Crohn's disease. Author(s): Yamamoto T, Mylonakis E, Keighley MR. Source: American Journal of Surgery. 2001 March; 181(3): 265-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376583&dopt=Abstract

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Open clinical trial of rifabutin and clarithromycin therapy in Crohn's disease. Author(s): Shafran I, Kugler L, El-Zaatari FA, Naser SA, Sandoval J. Source: Dig Liver Dis. 2002 January; 34(1): 22-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930899&dopt=Abstract

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Open label trial of oral clarithromycin in active Crohn's disease. Author(s): Leiper K, Morris AI, Rhodes JM. Source: Alimentary Pharmacology & Therapeutics. 2000 June; 14(6): 801-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10848665&dopt=Abstract

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Operative and environmental risk factors for recurrence of Crohn's disease. Author(s): Moskovitz D, McLeod RS, Greenberg GR, Cohen Z. Source: International Journal of Colorectal Disease. 1999 November; 14(4-5): 224-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10647631&dopt=Abstract

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Optimal cases and sites to search for primary microbial agents in Crohn's disease. Author(s): Chiba M, Nakamura T, Hoshina S, Kitagawa Y. Source: Gastroenterology. 2001 March; 120(4): 1066-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11265672&dopt=Abstract

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Optimum duration of treatment with 6-mercaptopurine for Crohn's disease. Author(s): Kim PS, Zlatanic J, Korelitz BI, Gleim GW. Source: The American Journal of Gastroenterology. 1999 November; 94(11): 3254-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566725&dopt=Abstract

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Oral aspects of Crohn's disease. Author(s): Scheper HJ, Brand HS. Source: Int Dent J. 2002 June; 52(3): 163-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090267&dopt=Abstract

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Oral budesonide approved for active Crohn's disease. Author(s): Thompson CA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 December 1; 58(23): 2229. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763799&dopt=Abstract

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Oral contraceptive use and the clinical course of Crohn's disease: a prospective cohort study. Author(s): Cosnes J, Carbonnel F, Carrat F, Beaugerie L, Gendre JP. Source: Gut. 1999 August; 45(2): 218-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403733&dopt=Abstract

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Oral delayed-release mesalazine: a review of its use in ulcerative colitis and Crohn's disease. Author(s): Prakash A, Markham A. Source: Drugs. 1999 March; 57(3): 383-408. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193690&dopt=Abstract

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Oral lesions in Crohn's disease: review of the literature with case report. Author(s): Lee CY, Tomich CE. Source: Hawaii Dent J. 1995 June; 26(6): 11-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910642&dopt=Abstract

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Oral mesalazine for the treatment of Crohn's disease: clinical efficacy with respect to pharmacokinetic properties. Author(s): Tromm A, Griga T, May B. Source: Hepatogastroenterology. 1999 November-December; 46(30): 3124-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10626173&dopt=Abstract

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Oral nutritional supplementation is effective in the maintenance of remission in Crohn's disease. Author(s): Verma S, Kirkwood B, Brown S, Giaffer MH. Source: Dig Liver Dis. 2000 December; 32(9): 769-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215556&dopt=Abstract

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Oral staphylococcal mucositis: A new clinical entity in orofacial granulomatosis and Crohn's disease. Author(s): Gibson J, Wray D, Bagg J. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2000 February; 89(2): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10673652&dopt=Abstract

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Oral tacrolimus (FK 506) in Crohn's disease complicated by fistulae of the perineum. Author(s): Ierardi E, Principi M, Rendina M, Francavilla R, Ingrosso M, Pisani A, Amoruso A, Panella C, Francavilla A. Source: Journal of Clinical Gastroenterology. 2000 March; 30(2): 200-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10730928&dopt=Abstract

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Oral tacrolimus long-term therapy in patients with Crohn's disease and steroid resistance. Author(s): Ierardi E, Principi M, Francavilla R, Pisani A, Rendina M, Ingrosso M, Guglielmi FW, Panella C, Francavilla A. Source: Alimentary Pharmacology & Therapeutics. 2001 March; 15(3): 371-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207512&dopt=Abstract

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Ornithine decarboxylase in colonic mucosa from patients with moderate or severe Crohn's disease and ulcerative colitis. Author(s): Ricci G, Stabellini G, Bersani G, Marangoni G, Fabbri P, Gentili G, Alvisi V. Source: European Journal of Gastroenterology & Hepatology. 1999 August; 11(8): 903-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10514125&dopt=Abstract

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Orocecal transit time and bacterial overgrowth in patients with Crohn's disease. Author(s): Castiglione F, Del Vecchio Blanco G, Rispo A, Petrelli G, Amalfi G, Cozzolino A, Cuccaro I, Mazzacca G. Source: Journal of Clinical Gastroenterology. 2000 July; 31(1): 63-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914780&dopt=Abstract

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Orofacial granulomatosis as initial manifestation of Crohn's disease: a report of two cases. Author(s): Girlich C, Bogenrieder T, Palitzsch KD, Scholmerich J, Lock G. Source: European Journal of Gastroenterology & Hepatology. 2002 August; 14(8): 873-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172408&dopt=Abstract

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Orofacial granulomatosis as the initial presentation of Crohn's disease in an adolescent. Author(s): Bogenrieder T, Rogler G, Vogt T, Landthaler M, Stolz W. Source: Dermatology (Basel, Switzerland). 2003; 206(3): 273-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673090&dopt=Abstract

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Osteonecrosis in a patient with Crohn's disease unrelated to corticosteroid use. Author(s): Khan A, Illiffe G, Houston DS, Bernstein CN. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 November; 15(11): 765-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11727007&dopt=Abstract

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Osteonecrosis, corticosteroid use and Crohn's disease: evidence-based medicine versus civil law. Author(s): Shaffer EA, Corenblum EB. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 February; 14(2): 91-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694280&dopt=Abstract

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Osteopenia and osteoporosis in Crohn's disease: prevalence in a Dutch populationbased cohort. Author(s): Schoon EJ, van Nunen AB, Wouters RS, Stockbrugger RW, Russel MG. Source: Scandinavian Journal of Gastroenterology. Supplement. 2000; (232): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232491&dopt=Abstract

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Osteopenia in Puerto Ricans with Crohn's disease. Author(s): Chinea B, Rosa A, Oharriz JJ, Ramirez M, Haddock L, Perez C, Torres EA. Source: P R Health Sci J. 2000 December; 19(4): 329-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293884&dopt=Abstract

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Osteoporosis: an unusual presentation of childhood Crohn's disease. Author(s): Thearle M, Horlick M, Bilezikian JP, Levy J, Gertner JM, Levine LS, Harbison M, Berdon W, Oberfield SE. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 June; 85(6): 2122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852438&dopt=Abstract

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Outcome of Crohn's disease diagnosed before two years of age. Author(s): Marx G, Seidman EG, Martin SR, Deslandres C. Source: The Journal of Pediatrics. 2002 April; 140(4): 470-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006965&dopt=Abstract

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Outcome of ileal pouch after secondary diagnosis of Crohn's disease. Author(s): Peyregne V, Francois Y, Gilly FN, Descos JL, Flourie B, Vignal J. Source: International Journal of Colorectal Disease. 2000 February; 15(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766091&dopt=Abstract

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Outcome of strictureplasty for duodenal Crohn's disease. Author(s): Yamamoto T, Bain IM, Connolly AB, Allan RN, Keighley MR. Source: The British Journal of Surgery. 1999 February; 86(2): 259-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10100799&dopt=Abstract

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Ovarian vein thrombosis associated with Crohn's disease: a case report. Author(s): Marcovici I, Goldberg E. Source: American Journal of Obstetrics and Gynecology. 2000 March; 182(3): 743-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739545&dopt=Abstract

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Over-utilization of the J delta 3 gene-segment in Crohn's disease. Author(s): Landau SB, Probert CS, Stevens CA, Balk SP, Blumberg RS. Source: J Clin Lab Immunol. 1996; 48(1): 33-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332632&dopt=Abstract

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Overview: Nod2, cause of, or contributor to, Crohn's disease. Author(s): Punchard NA. Source: Curr Opin Investig Drugs. 2001 October; 2(10): 1378-81. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890351&dopt=Abstract

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Oxidative stress, vitamin A and vitamin E behaviour in patients submitted to conservative surgery for complicated Crohn's disease. Author(s): Sampietro GM, Cristaldi M, Cervato G, Maconi G, Danelli P, Cervellione R, Rovati M, Porro GB, Cestaro B, Taschieri AM. Source: Dig Liver Dis. 2002 October; 34(10): 696-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469796&dopt=Abstract

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Paediatric Crohn's disease: a radiological review. Author(s): Ali SI, Carty HM. Source: European Radiology. 2000; 10(7): 1085-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11003403&dopt=Abstract

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Pancreatitis as a presenting manifestation of pediatric Crohn's disease: a report of three cases. Author(s): Kugathasan S, Halabi I, Telega G, Werlin SL. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 July; 35(1): 96-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142820&dopt=Abstract

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Paracoccidioidomycosis masquerading as Crohn's disease. Author(s): Cury MS, Ribeiro BS, Costa PP, de Lima VM, Mizsputen SJ, Ferrari AP. Source: Gastrointestinal Endoscopy. 2000 June; 51(6): 722-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10840309&dopt=Abstract

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Pathogenesis and therapeutic aspects of Crohn's disease. Author(s): Selby W. Source: Veterinary Microbiology. 2000 December 20; 77(3-4): 505-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11118735&dopt=Abstract

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Pathogenic Yersinia DNA is detected in bowel and mesenteric lymph nodes from patients with Crohn's disease. Author(s): Lamps LW, Madhusudhan KT, Havens JM, Greenson JK, Bronner MP, Chiles MC, Dean PJ, Scott MA. Source: The American Journal of Surgical Pathology. 2003 February; 27(2): 220-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548169&dopt=Abstract

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Patients with refractory Crohn's disease or ulcerative colitis respond to dehydroepiandrosterone: a pilot study. Author(s): Andus T, Klebl F, Rogler G, Bregenzer N, Scholmerich J, Straub RH. Source: Alimentary Pharmacology & Therapeutics. 2003 February; 17(3): 409-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562454&dopt=Abstract

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Pattern dystrophy of the retinal pigment epithelium in Crohn's disease. A case report. Author(s): De Franceschi P, Costagliola C, Soreca E, Di Meo A, Giacoia A, Romano A. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2000; 214(6): 441-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054008&dopt=Abstract

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Pattern of apoptosis in Crohn's disease: a singular aspect? Author(s): Ierardi E, Principi M, Burattini O, Marangi S, Panarese A, Francavilla A. Source: Dig Liver Dis. 2001 October; 33(7): 614-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11816555&dopt=Abstract

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PCR detection of Mycobacterium paratuberculosis in Crohn's disease granulomas isolated by laser capture microdissection. Author(s): Ryan P, Bennett MW, Aarons S, Lee G, Collins JK, O'Sullivan GC, O'Connell J, Shanahan F. Source: Gut. 2002 November; 51(5): 665-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377804&dopt=Abstract

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Pediatric Crohn's disease: risk factors for postoperative recurrence. Author(s): Baldassano RN, Han PD, Jeshion WC, Berlin JA, Piccoli DA, Lautenbach E, Mick R, Lichtenstein GR. Source: The American Journal of Gastroenterology. 2001 July; 96(7): 2169-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11467649&dopt=Abstract

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Perianal Crohn's disease in infancy. Author(s): Pashankar D, Schreiber RA, Israel DM. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 July; 31(1): 80-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896077&dopt=Abstract

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Perianal Crohn's disease masquerading as perianal warts. Author(s): Garg M, Kawsar M, Forster GE, Medows NJ. Source: Sexually Transmitted Infections. 2002 August; 78(4): 302-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181473&dopt=Abstract

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Perianal Crohn's disease. Author(s): Morales MS, Marini M, Caminero M, Caglio P. Source: International Journal of Dermatology. 2000 August; 39(8): 616-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971732&dopt=Abstract

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Perianal Hodgkin's lymphoma complicating Crohn's disease. Author(s): Sivarajasingham N, Adams SA, Smith ME, Hosie KB. Source: International Journal of Colorectal Disease. 2003 March; 18(2): 174-6. Epub 2002 November 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548423&dopt=Abstract

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Persistent perineal sinus after proctectomy for Crohn's disease; simplified repair using skin flap. Author(s): Bascom T, Bascom JU. Source: American Journal of Surgery. 2002 July; 184(1): 85; Author Reply 85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135729&dopt=Abstract

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Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn's disease treated with infliximab. Author(s): Mascheretti S, Hampe J, Kuhbacher T, Herfarth H, Krawczak M, Folsch UR, Schreiber S. Source: The Pharmacogenomics Journal. 2002; 2(2): 127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049175&dopt=Abstract

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Pharmacogenomics of response to anti-tumor necrosis factor therapy in patients with Crohn's disease. Author(s): Shetty A, Forbes A. Source: American Journal of Pharmacogenomics : Genomics-Related Research in Drug Development and Clinical Practice. 2002; 2(4): 215-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421092&dopt=Abstract

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Pharmacokinetics of budesonide controlled ileal release capsules in children and adults with active Crohn's disease. Author(s): Lundin PD, Edsbacker S, Bergstrand M, Ejderhamn J, Linander H, Hogberg L, Persson T, Escher JC, Lindquist B. Source: Alimentary Pharmacology & Therapeutics. 2003 January; 17(1): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492736&dopt=Abstract

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Pneumatosis cystoides intestinalis in Crohn's disease. Author(s): Breitinger A, Kozarek R, Hauptman E. Source: Gastrointestinal Endoscopy. 2003 February; 57(2): 241. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556794&dopt=Abstract

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Polyethylene glycol and contrast-enhanced MRI of Crohn's disease in children: preliminary experience. Author(s): Magnano G, Granata C, Barabino A, Magnaguagno F, Rossi U, Calevo MG, Toma P. Source: Pediatric Radiology. 2003 June; 33(6): 385-91. Epub 2003 April 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682793&dopt=Abstract

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Polymorphism of CC chemokine receptors CCR2 and CCR5 in Crohn's disease. Author(s): Herfarth H, Pollok-Kopp B, Goke M, Press A, Oppermann M. Source: Immunology Letters. 2001 June 1; 77(2): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377705&dopt=Abstract

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Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn's disease, respectively. Author(s): Sashio H, Tamura K, Ito R, Yamamoto Y, Bamba H, Kosaka T, Fukui S, Sawada K, Fukuda Y, Tamura K, Satomi M, Shimoyama T, Furuyama J. Source: Immunogenetics. 2002 March; 53(12): 1020-7. Epub 2002 February 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904678&dopt=Abstract

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Polymorphonuclear leukocyte-elastase in Crohn's disease: correlation with 99mtechnetium hexamethyl propylene amine oxime leukocyte scintigraphy. Author(s): Dhote R, Dhote-Burger P, Thevenot T, Devaux JY, Beades E, Richard B, Christoforov B. Source: Journal of Clinical Gastroenterology. 2000 September; 31(2): 152-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10993433&dopt=Abstract

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Positive IS900 in situ hybridization signals as evidence for role of Mycobacterium avium subsp. paratuberculosis in etiology of Crohn's disease. Author(s): Roholl PJ, Herrewegh A, van Soolingen D. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 3112; Author Reply 3112-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149398&dopt=Abstract

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Post-liver transplant Crohn's disease: graft tolerance but not self-tolerance? Author(s): Ramji A, Owen DA, Erb SR, Scudamore CH, Yoshida EM. Source: Digestive Diseases and Sciences. 2002 March; 47(3): 522-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911336&dopt=Abstract

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Potential therapeutic role for cytokine or adhesion molecule manipulation in Crohn's disease: in the shadow of infliximab? Author(s): Shand A, Forbes A. Source: International Journal of Colorectal Disease. 2003 January; 18(1): 1-11. Epub 2002 August 14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458374&dopt=Abstract

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Predictors of response to infliximab in patients with Crohn's disease. Author(s): Parsi MA, Achkar JP, Richardson S, Katz J, Hammel JP, Lashner BA, Brzezinski A. Source: Gastroenterology. 2002 September; 123(3): 707-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198696&dopt=Abstract

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Preliminary study of ciprofloxacin in active Crohn's disease. Author(s): Arnold GL, Beaves MR, Pryjdun VO, Mook WJ. Source: Inflammatory Bowel Diseases. 2002 January; 8(1): 10-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837933&dopt=Abstract

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Preoperative characteristics and postoperative behavior of bowel wall on risk of recurrence after conservative surgery in Crohn's disease: a prospective study. Author(s): Maconi G, Sampietro GM, Cristaldi M, Danelli PG, Russo A, Porro GB, Taschieri AM. Source: Annals of Surgery. 2001 March; 233(3): 345-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11224621&dopt=Abstract

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Preoperative management is more important than choice of sutured or stapled anastomosis in Crohn's disease. Author(s): Smedh K, Andersson M, Johansson H, Hagberg T. Source: The European Journal of Surgery = Acta Chirurgica. 2002; 168(3): 154-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182240&dopt=Abstract

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Presence of group IIa secretory phospholipase A2 in mast cells and macrophages in normal human ileal submucosa and in Crohn's disease. Author(s): Lilja I, Gustafson-Svard C, Franzen L, Sjodahl R, Andersen S, Johansen B. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2000 December; 38(12): 1231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205686&dopt=Abstract

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Prevalence of Helicobacter pylori infection and correlation between severity of upper gastrointestinal lesions and H. pylori infection in Japanese patients with Crohn's disease. Author(s): Matsumura M, Matsui T, Hatakeyama S, Matake H, Uno H, Sakurai T, Yao T, Oishi T, Iwashita A, Fujioka T. Source: Journal of Gastroenterology. 2001 November; 36(11): 740-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757745&dopt=Abstract

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Preventing antibodies to infliximab in patients with Crohn's disease: optimize not immunize. Author(s): Sandborn WJ. Source: Gastroenterology. 2003 April; 124(4): 1140-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671907&dopt=Abstract

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Prevention of pancreatitis by weekly amylase assay in patients with Crohn's disease treated with azathioprine. Author(s): Castiglione F, Del Vecchio Blanco G, Rispo A, Mazzacca G. Source: The American Journal of Gastroenterology. 2000 September; 95(9): 2394-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007256&dopt=Abstract

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Prevention of postoperative recurrence in Crohn's disease. Author(s): D'Haens G. Source: Current Gastroenterology Reports. 1999 December; 1(6): 476-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10980989&dopt=Abstract

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Prevention of relapse of Crohn's disease. Author(s): Sutherland LR. Source: Inflammatory Bowel Diseases. 2000 November; 6(4): 321-8; Discussion 329. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149565&dopt=Abstract

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Primary chronic interstitial nephritis in Crohn's disease. Author(s): Izzedine H, Simon J, Piette AM, Lucsko M, Baumelou A, Charitanski D, Kernaonet E, Baglin AC, Deray G, Beaufils H. Source: Gastroenterology. 2002 November; 123(5): 1436-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404216&dopt=Abstract

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Primary closure of complicated perineal wounds with myocutaneous and fasciocutaneous flaps after proctectomy for Crohn's disease. Author(s): Hurst RD, Gottlieb LJ, Crucitti P, Melis M, Rubin M, Michelassi F. Source: Surgery. 2001 October; 130(4): 767-72; Discussion 772-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11602910&dopt=Abstract

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Primary intestinal lymphoma complicating Crohn's disease. Author(s): Hall CH Jr, Shamma M. Source: Journal of Clinical Gastroenterology. 2003 April; 36(4): 332-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642741&dopt=Abstract

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Prior bowel resections, perianal disease, and a high initial Crohn's disease activity index are associated with corticosteroid resistance in active Crohn's disease. Author(s): Gelbmann CM, Rogler G, Gross V, Gierend M, Bregenzer N, Andus T, Scholmerich J. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1438-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094862&dopt=Abstract

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Progress in treatment for Crohn's disease. Author(s): Brzezinski A. Source: The American Journal of Gastroenterology. 2001 March; 96(3): 626-7. Erratum In: Am J Gastroenterol 2001 September; 96(9): 2809. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280525&dopt=Abstract

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Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease. Author(s): Kugathasan S, Werlin SL, Martinez A, Rivera MT, Heikenen JB, Binion DG. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095340&dopt=Abstract

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Prolonged duration of response to infliximab in early pediatric Crohn's disease. Author(s): Kugathasan S. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 September; 33 Suppl 1: S40-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685975&dopt=Abstract

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Prospective assessment of Cleveland Global Quality of Life (CGQL) as a novel marker of quality of life and disease activity in Crohn's disease. Author(s): Kiran RP, Delaney CP, Senagore AJ, O'Brien-Ermlich B, Mascha E, Thornton J, Fazio VW. Source: The American Journal of Gastroenterology. 2003 August; 98(8): 1783-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907333&dopt=Abstract

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Prospective comparison of endosonography, magnetic resonance imaging and surgical findings in anorectal fistula and abscess complicating Crohn's disease. Author(s): Zbar AP, deSouza NM. Source: The British Journal of Surgery. 1999 August; 86(8): 1093-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10498422&dopt=Abstract

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Prospective, randomized trial comparing laparoscopic vs. conventional surgery for refractory ileocolic Crohn's disease. Author(s): Milsom JW, Hammerhofer KA, Bohm B, Marcello P, Elson P, Fazio VW. Source: Diseases of the Colon and Rectum. 2001 January; 44(1): 1-8; Discussion 8-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805557&dopt=Abstract

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Prostatic abscess in young males: a rare complication of Crohn's disease. Author(s): Yamaguchi M, Kujiraoka Y, Saida Y, Ikezawa K, Uchida K, Itai Y. Source: Abdominal Imaging. 2001 July-August; 26(4): 423-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11441558&dopt=Abstract

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Protagonist: Crohn's disease recurrence can be prevented after ileal resection. Author(s): Rutgeerts P. Source: Gut. 2002 August; 51(2): 152-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117870&dopt=Abstract

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Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn's disease. Author(s): Radford-Smith GL, Edwards JE, Purdie DM, Pandeya N, Watson M, Martin NG, Green A, Newman B, Florin TH. Source: Gut. 2002 December; 51(6): 808-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427781&dopt=Abstract

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Proximal Crohn's disease: review of the clinicopathologic features and therapy. Author(s): van Hogezand RA, Witte AM, Veenendaal RA, Wagtmans MJ, Lamers CB. Source: Inflammatory Bowel Diseases. 2001 November; 7(4): 328-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720325&dopt=Abstract

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Pseudomonas fluorescens encodes the Crohn's disease-associated I2 sequence and Tcell superantigen. Author(s): Wei B, Huang T, Dalwadi H, Sutton CL, Bruckner D, Braun J. Source: Infection and Immunity. 2002 December; 70(12): 6567-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438326&dopt=Abstract

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Psoas abscess complicating Crohn's disease: report of a case. Author(s): Ogihara M, Masaki T, Watanabe T, Hatano K, Matsuda K, Yahagi N, Ichinose M, Seichi A, Muto T. Source: Surgery Today. 2000; 30(8): 759-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10955745&dopt=Abstract

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Psychological disorder and severity of inflammatory bowel disease predict healthrelated quality of life in ulcerative colitis and Crohn's disease. Author(s): Guthrie E, Jackson J, Shaffer J, Thompson D, Tomenson B, Creed F. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 1994-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190166&dopt=Abstract

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Pulmonary migratory infiltrates and pachypleuritis in a patient with Crohn's disease. Author(s): Faller M, Gasser B, Massard G, Pauli G, Quoix E. Source: Respiration; International Review of Thoracic Diseases. 2000; 67(4): 459-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10940806&dopt=Abstract

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Puzzling fever and neutropenia in a patient with Crohn's disease post-coronary artery bypass surgery. Author(s): Rotman-Pikielny P, Levy Y. Source: Isr Med Assoc J. 2002 December; 4(12): 1158-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516918&dopt=Abstract

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Pyostomatitis vegetans as an early sign of reactivation of Crohn's disease: a case report. Author(s): Ayangco L, Rogers RS 3rd, Sheridan PJ. Source: J Periodontol. 2002 December; 73(12): 1512-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546102&dopt=Abstract

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Quality of life after surgical therapy of small bowel stenosis in Crohn's disease. Author(s): Broering DC, Eisenberger CF, Koch A, Bloechle C, Knoefel WT, Izbicki JR. Source: Digestive Surgery. 2001; 18(2): 124-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351157&dopt=Abstract

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Quality of life improves within 30 days of surgery for Crohn's disease. Author(s): Delaney CP, Kiran RP, Senagore AJ, O'Brien-Ermlich B, Church J, Hull TL, Remzi FH, Fazio VW. Source: Journal of the American College of Surgeons. 2003 May; 196(5): 714-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742203&dopt=Abstract

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Quality of life in children with Crohn's disease: a pilot study. Author(s): Akobeng AK, Suresh-Babu MV, Firth D, Miller V, Mir P, Thomas AG. Source: Journal of Pediatric Gastroenterology and Nutrition. 1999 April; 28(4): S37-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10204523&dopt=Abstract

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Quality of life in Korean patients with inflammatory bowel diseases: ulcerative colitis, Crohn's disease and intestinal Behcet's disease. Author(s): Kim WH, Cho YS, Yoo HM, Park IS, Park EC, Lim JG. Source: International Journal of Colorectal Disease. 1999 February; 14(1): 52-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10207731&dopt=Abstract

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Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group. Author(s): Irvine EJ, Greenberg GR, Feagan BG, Martin F, Sutherland LR, Thomson AB, Nilsson LG, Persson T. Source: Inflammatory Bowel Diseases. 2000 August; 6(3): 181-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961590&dopt=Abstract

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Quantitation of chemokines (MDC, TARC) expression in mucosa from Crohn's disease and ulcerative colitis. Author(s): Jugde F, Alizadeh M, Boissier C, Chantry D, Siproudhis L, Corbinais S, Quelvennec E, Dyard F, Campion JP, Gosselin M, Bretagne JF, Semana G, Heresbach D. Source: Eur Cytokine Netw. 2001 July-September; 12(3): 468-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566628&dopt=Abstract

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Quantitative ultrasound of the proximal phalanges and dual-energy X-ray absorptiometry in Crohn's disease patients with osteopenia. Author(s): von Tirpitz C, Klaus J, Steinkamp M, Mason R, Kratzer W, Adler G, Rieber A, Reinshagen M. Source: Journal of Gastroenterology. 2003; 38(3): 238-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673446&dopt=Abstract

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Quiz case. Ulcerative colitis? Crohn's disease? Author(s): Mako EK, Mester AR, Gyorke T, Tarjan Z, Karlinger K. Source: European Journal of Radiology. 2000 September; 35(3): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11203025&dopt=Abstract

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Radiologic and endoscopic diagnosis of Crohn's disease. Author(s): Rubesin SE, Scotiniotis I, Birnbaum BA, Ginsberg GG. Source: The Surgical Clinics of North America. 2001 February; 81(1): 39-70, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218169&dopt=Abstract

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Randomized controlled trial of clarithromycin and ethambutol in the treatment of Crohn's disease. Author(s): Goodgame RW, Kimball K, Akram S, Ike E, Ou CN, Sutton F, Graham D. Source: Alimentary Pharmacology & Therapeutics. 2001 December; 15(12): 1861-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11736715&dopt=Abstract

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Randomized, controlled trial of recombinant human interleukin-11 in patients with active Crohn's disease. Author(s): Sands BE, Winston BD, Salzberg B, Safdi M, Barish C, Wruble L, Wilkins R, Shapiro M, Schwertschlag US; RHIL-11 Crohn's Study group. Source: Alimentary Pharmacology & Therapeutics. 2002 March; 16(3): 399-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876692&dopt=Abstract

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Rapid response of severe refractory metastatic Crohn's disease to infliximab. Author(s): Miller AM, Elliott PR, Fink R, Connell W. Source: Journal of Gastroenterology and Hepatology. 2001 August; 16(8): 940-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555113&dopt=Abstract

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RE: Development of an assay for antibodies to Saccharomyces cerevisiae: Easy, cheap and specific for Crohn's disease. Author(s): Vermeire S, Wild G. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 December; 15(12): 841-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773951&dopt=Abstract

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Re: Fefferman et al.--"Recurrence" of chronic pancreatitis appearing on a patient with underlying Crohn's disease. Author(s): Triantafillidis JK, Cheracakis P. Source: The American Journal of Gastroenterology. 2002 March; 97(3): 761-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922579&dopt=Abstract

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Re: Triantafillidis et al.--Acute idiopathic pancreatitis complicating active Crohn's disease: favorable response to infliximab treatment. Author(s): Fefferman DS, Alsahli M, Lodhavia PJ, Shah SA, Farrell RJ. Source: The American Journal of Gastroenterology. 2001 August; 96(8): 2510-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513207&dopt=Abstract

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Recombinant interleukin 10 for the treatment of active Crohn's disease: lessons in biologic therapy. Author(s): Bickston SJ, Cominelli F. Source: Gastroenterology. 2000 December; 119(6): 1781-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113101&dopt=Abstract

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Rectoanal motility in Crohn's disease patients. Author(s): Chrysos E, Athanasakis E, Tsiaoussis J, Zoras O, Nickolopoulos A, Vassilakis JS, Xynos E. Source: Diseases of the Colon and Rectum. 2001 October; 44(10): 1509-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598482&dopt=Abstract

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Recurrence after abdominal surgery for Crohn's disease: relationship to disease site and surgical procedure. Author(s): Borley NR, Mortensen NJ, Chaudry MA, Mohammed S, Warren BF, George BD, Clark T, Jewell DP, Kettlewell MG. Source: Diseases of the Colon and Rectum. 2002 March; 45(3): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12068198&dopt=Abstract

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Recurrence of gallstone ileus with Crohn's disease. Author(s): La Meir M, Van Molhem Y. Source: Acta Chir Belg. 2001 January-February; 101(1): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301946&dopt=Abstract

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Recurrent atypical myxoid fibroepithelial polyp associated with vulvar Crohn's disease. Author(s): Papiez JS, Hassenein A, Wilkinson E, Meynen CA. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 2001 July; 20(3): 271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444204&dopt=Abstract

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Recurrent myopericarditis in association with Crohn's disease. Author(s): Hyttinen L, Kaipiainen-Seppanen O, Halinen M. Source: Journal of Internal Medicine. 2003 March; 253(3): 386-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603508&dopt=Abstract

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Recurrent pneumonia from an ileobronchial fistula complicating Crohn's disease. Author(s): Gumbo T, Rice TW, Mawhorter S. Source: Journal of Clinical Gastroenterology. 2001 April; 32(4): 365-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11276288&dopt=Abstract

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Recurrent venous thromboses, anti-cardiolipin antibodies and Crohn's disease. Author(s): Thong BY, Chng HH, Ang CL, Ho MS. Source: Qjm : Monthly Journal of the Association of Physicians. 2002 April; 95(4): 253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937654&dopt=Abstract

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Red cell fatty acid profile and elemental diet in childhood Crohn's disease. Author(s): Sagher FA, Miller V, Ward IC. Source: Saudi Med J. 2001 October; 22(10): 931. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744960&dopt=Abstract

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Redox imbalance in Crohn's disease intestinal smooth muscle cells causes NFkappaB-mediated spontaneous interleukin-8 secretion. Author(s): Natarajan R, Ghosh S, Fisher BJ, Diegelmann RF, Willey A, Walsh S, Graham MF, Fowler AA 3rd. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2001 June; 21(6): 349-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440632&dopt=Abstract

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Reduction of colorectal cancer risk in patients with Crohn's disease. Author(s): Lichtenstein GR. Source: Reviews in Gastroenterological Disorders. 2002; 2 Suppl 2: S16-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478240&dopt=Abstract

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Regional variation of the alphabeta T cell repertoire in the colon of healthy individuals and patients with Crohn's disease. Author(s): May E, Lambert C, Holtmeier W, Hennemann A, Zeitz M, Duchmann R. Source: Human Immunology. 2002 June; 63(6): 467-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12039522&dopt=Abstract

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Relationship between anamnestic evidence of appendectomy and onset and clinical course of Crohn's disease. Author(s): Caserta L, de Filippo FR, Riegler G. Source: The American Journal of Gastroenterology. 2002 January; 97(1): 207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811167&dopt=Abstract

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Remicade does not abolish the need for surgery in fistulizing Crohn's disease. Author(s): Poritz LS, Rowe WA, Koltun WA. Source: Diseases of the Colon and Rectum. 2002 June; 45(6): 771-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072629&dopt=Abstract

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Remission induced by a new specific oral polymeric diet in children with Crohn's disease. Author(s): Fell JM, Paintin M, Donnet-Hughes A, Arnaud-Battandier F, MacDonald TT, Walker-Smith JA. Source: Nestle Nutr Workshop Ser Clin Perform Programme. 1999; 2: 187-96; Discussion 196-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490622&dopt=Abstract

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Remission maintenance by tioguanine in chronic active Crohn's disease. Author(s): Herrlinger KR, Deibert P, Schwab M, Kreisel W, Fischer C, Fellermann K, Stange EF. Source: Alimentary Pharmacology & Therapeutics. 2003 June 15; 17(12): 1459-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823147&dopt=Abstract

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Remission of Crohn's disease on bupropion. Author(s): Kast RE, Altschuler EL. Source: Gastroenterology. 2001 November; 121(5): 1260-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706830&dopt=Abstract

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Renal calculus at presentation in a child with Crohn's disease. Author(s): Joy HM, Fairhurst JJ, Beattie RM. Source: Pediatric Radiology. 2003 April; 33(4): 250-2. Epub 2003 February 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709754&dopt=Abstract

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Reoperations at the ileostomy in Crohn's disease reflect inflammatory activity rather than surgical stoma complications alone. Author(s): Ecker KW, Gierend M, Kreissler-Haag D, Feifel G. Source: International Journal of Colorectal Disease. 2001 April; 16(2): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11355322&dopt=Abstract

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Replacement of conventional glucocorticoids by oral pH-modified release budesonide in active and inactive Crohn's disease: results of an open, prospective, multicenter trial. Author(s): Andus T, Gross V, Caesar I, Schulz HJ, Lochs H, Strohm WD, Gierend M, Weber A, Ewe K, Scholmerich J; German/Austrian Budesonide Study Group. Source: Digestive Diseases and Sciences. 2003 February; 48(2): 373-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643618&dopt=Abstract

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Resection margins in Crohn's disease. Author(s): Wolff BG. Source: The British Journal of Surgery. 2001 June; 88(6): 771-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412245&dopt=Abstract

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Resolution of nephrotic syndrome caused by amyloidosis following surgery for Crohn's disease. Author(s): Leiper K, Howse ML, Bell GM. Source: Hosp Med. 2000 November; 61(11): 802-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198753&dopt=Abstract

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Response of fistulating Crohn's disease to infliximab treatment assessed by magnetic resonance imaging. Author(s): Bell SJ, Halligan S, Windsor AC, Williams AB, Wiesel P, Kamm MA. Source: Alimentary Pharmacology & Therapeutics. 2003 February; 17(3): 387-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562451&dopt=Abstract

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Response to infliximab is related to disease duration in paediatric Crohn's disease. Author(s): Lionetti P, Bronzini F, Salvestrini C, Bascietto C, Canani RB, De Angelis GL, Guariso G, Martelossi S, Papadatou B, Barabino A. Source: Alimentary Pharmacology & Therapeutics. 2003 August 15; 18(4): 425-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940928&dopt=Abstract

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Response to infliximab treatment in Crohn's disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials. Author(s): Mascheretti S, Hampe J, Croucher PJ, Nikolaus S, Andus T, Schubert S, Olson A, Bao W, Folsch UR, Schreiber S. Source: Pharmacogenetics. 2002 October; 12(7): 509-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360101&dopt=Abstract

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Response, relapse and mucosal immune regulation after infliximab treatment in fistulating Crohn's disease. Author(s): Agnholt J, Dahlerup JF, Buntzen S, Tottrup A, Nielsen SL, Lundorf E. Source: Alimentary Pharmacology & Therapeutics. 2003 March 1; 17(5): 703-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641520&dopt=Abstract

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Retinal vein thrombosis after infliximab (Remicade) treatment for Crohn's disease. Author(s): Puli SR, Benage DD. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 939-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738486&dopt=Abstract

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Review article: a critical approach to new forms of treatment of Crohn's disease and ulcerative colitis. Author(s): Seegers D, Bouma G, Pena AS. Source: Alimentary Pharmacology & Therapeutics. 2002 July; 16 Suppl 4: 53-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047261&dopt=Abstract

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Review article: biological agents in the treatment of Crohn's disease. Author(s): Caprilli R, Viscido A, Guagnozzi D. Source: Alimentary Pharmacology & Therapeutics. 2002 September; 16(9): 1579-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197837&dopt=Abstract

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Review article: Crohn's disease: monitoring disease activity. Author(s): Sostegni R, Daperno M, Scaglione N, Lavagna A, Rocca R, Pera A. Source: Alimentary Pharmacology & Therapeutics. 2003 June; 17 Suppl 2: 11-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786607&dopt=Abstract

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Review article: indication and type of surgery in Crohn's disease. Author(s): Poggioli G, Pierangeli F, Laureti S, Ugolini F. Source: Alimentary Pharmacology & Therapeutics. 2002 July; 16 Suppl 4: 59-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047262&dopt=Abstract

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Review article: is clinical remission the optimum therapeutic goal in the treatment of Crohn's disease? Author(s): Arnott ID, Watts D, Ghosh S. Source: Alimentary Pharmacology & Therapeutics. 2002 May; 16(5): 857-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966492&dopt=Abstract

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Review article: maintenance treatment of Crohn's disease. Author(s): Biancone L, Tosti C, Fina D, Fantini M, De Nigris F, Geremia A, Pallone F. Source: Alimentary Pharmacology & Therapeutics. 2003 June; 17 Suppl 2: 31-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786610&dopt=Abstract

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Review article: medical treatment of active Crohn's disease. Author(s): Scribano ML, Prantera C. Source: Alimentary Pharmacology & Therapeutics. 2002 July; 16 Suppl 4: 35-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047258&dopt=Abstract

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Review article: medical treatment of mild to moderately active Crohn's disease. Author(s): Lofberg R. Source: Alimentary Pharmacology & Therapeutics. 2003 June; 17 Suppl 2: 18-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786608&dopt=Abstract

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Review article: medical treatment of moderate to severe Crohn's disease. Author(s): Scribano M, Prantera C. Source: Alimentary Pharmacology & Therapeutics. 2003 June; 17 Suppl 2: 23-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786609&dopt=Abstract

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Review article: mild to moderate Crohn's disease--defining the basis for a new treatment algorithm. Author(s): Sandborn WJ, Feagan BG. Source: Alimentary Pharmacology & Therapeutics. 2003 August 1; 18(3): 263-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895211&dopt=Abstract

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Review article: monitoring the activity of Crohn's disease. Author(s): Biancone L, De Nigris F, Del Vecchio Blanco G, Monteleone I, Vavassori P, Geremia A, Pallone F. Source: Alimentary Pharmacology & Therapeutics. 2002 July; 16 Suppl 4: 29-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047257&dopt=Abstract

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Review article: Mycobacterium avium subsp. paratuberculosis as one cause of Crohn's disease. Author(s): Chamberlin W, Graham DY, Hulten K, El-Zimaity HM, Schwartz MR, Naser S, Shafran I, El-Zaatari FA. Source: Alimentary Pharmacology & Therapeutics. 2001 March; 15(3): 337-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207508&dopt=Abstract

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Review article: the immunoregulatory cytokine interleukin-10--a therapy for Crohn's disease? Author(s): Lindsay JO, Hodgson HJ. Source: Alimentary Pharmacology & Therapeutics. 2001 November; 15(11): 1709-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683684&dopt=Abstract

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Review article: the limitations of corticosteroid therapy in Crohn's disease. Author(s): Rutgeerts PJ. Source: Alimentary Pharmacology & Therapeutics. 2001 October; 15(10): 1515-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563990&dopt=Abstract

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Review article: the management of refractory Crohn's disease. Author(s): Rizzello F, Gionchetti P, Venturi A, Morselli C, Campieri M. Source: Alimentary Pharmacology & Therapeutics. 2002 July; 16 Suppl 4: 40-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047259&dopt=Abstract

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Review article: the management of severe Crohn's disease. Author(s): Parkes M, Jewell DP. Source: Alimentary Pharmacology & Therapeutics. 2001 May; 15(5): 563-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328250&dopt=Abstract

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Rho kinase blockade prevents inflammation via nuclear factor kappa B inhibition: evidence in Crohn's disease and experimental colitis. Author(s): Segain JP, Raingeard de la Bletiere D, Sauzeau V, Bourreille A, Hilaret G, Cario-Toumaniantz C, Pacaud P, Galmiche JP, Loirand G. Source: Gastroenterology. 2003 May; 124(5): 1180-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730857&dopt=Abstract

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Risk factors for intra-abdominal sepsis after surgery in Crohn's disease. Author(s): Yamamoto T, Allan RN, Keighley MR. Source: Diseases of the Colon and Rectum. 2000 August; 43(8): 1141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950014&dopt=Abstract

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Risk factors for low bone density in Crohn's disease. Author(s): Habtezion A, Silverberg MS, Parkes R, Mikolainis S, Steinhart AH. Source: Inflammatory Bowel Diseases. 2002 March; 8(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854605&dopt=Abstract

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Risk factors for surgery and recurrence in 907 patients with primary ileocaecal Crohn's disease. Author(s): Bernell O, Lapidus A, Hellers G. Source: The British Journal of Surgery. 2000 December; 87(12): 1697-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122187&dopt=Abstract

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Road traffic accident as an iatrogenic complication of steroid treatment in Crohn's disease. Author(s): Jacob R, Walsh C, Hunter JO. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2154-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190205&dopt=Abstract

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Role of electrogastrography in detecting motility disorders in children affected by chronic intestinal pseudo-obstruction and Crohn's disease. Author(s): Bracci F, Iacobelli BD, Papadatou B, Ferretti F, Lucchetti MC, Cianchi D, Francalanci P, Ponticelli A. Source: European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery . [et Al] = Zeitschrift Fur Kinderchirurgie. 2003 February; 13(1): 314. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664412&dopt=Abstract

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Role of granuloma in the immunopathogenesis of Crohn's disease. Author(s): Matsumoto T, Nakamura S, Jin-No Y, Sawa Y, Hara J, Oshitani N, Arakawa T, Otani H, Nagura H. Source: Digestion. 2001; 63 Suppl 1: 43-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173909&dopt=Abstract

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Role of tumor necrosis factor in Crohn's disease. Author(s): Ganesan S, Travis SP, Ahmad T, Jazrawi R. Source: Curr Opin Investig Drugs. 2002 September; 3(9): 1297-300. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498003&dopt=Abstract

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Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine. Author(s): Kaskas BA, Louis E, Hindorf U, Schaeffeler E, Deflandre J, Graepler F, Schmiegelow K, Gregor M, Zanger UM, Eichelbaum M, Schwab M. Source: Gut. 2003 January; 52(1): 140-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477776&dopt=Abstract

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Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Author(s): Schreiber S, Fedorak RN, Nielsen OH, Wild G, Williams CN, Nikolaus S, Jacyna M, Lashner BA, Gangl A, Rutgeerts P, Isaacs K, van Deventer SJ, Koningsberger JC, Cohard M, LeBeaut A, Hanauer SB. Source: Gastroenterology. 2000 December; 119(6): 1461-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113067&dopt=Abstract

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Safety and longterm efficacy of strictureplasty in 314 patients with obstructing small bowel Crohn's disease. Author(s): Dietz DW, Laureti S, Strong SA, Hull TL, Church J, Remzi FH, Lavery IC, Fazio VW. Source: Journal of the American College of Surgeons. 2001 March; 192(3): 330-7; Discussion 337-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245375&dopt=Abstract

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Safety and steroid-sparing experience using infliximab for Crohn's disease at a pediatric inflammatory bowel disease center. Author(s): Stephens MC, Shepanski MA, Mamula P, Markowitz JE, Brown KA, Baldassano RN. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 104-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526944&dopt=Abstract

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Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens. Author(s): Landers CJ, Cohavy O, Misra R, Yang H, Lin YC, Braun J, Targan SR. Source: Gastroenterology. 2002 September; 123(3): 689-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198693&dopt=Abstract

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Selective resistance of mucosal T-cell activation to immunosuppression in Crohn's disease. Author(s): Matsuura T, West GA, Levine AD, Fiocchi C. Source: Dig Liver Dis. 2000 August-September; 32(6): 484-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11057923&dopt=Abstract

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Self-assessment of sexual maturity status in children with Crohn's disease. Author(s): Schall JI, Semeao EJ, Stallings VA, Zemel BS. Source: The Journal of Pediatrics. 2002 August; 141(2): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183718&dopt=Abstract

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Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease. Author(s): Esters N, Vermeire S, Joossens S, Noman M, Louis E, Belaiche J, De Vos M, Van Gossum A, Pescatore P, Fiasse R, Pelckmans P, Reynaert H, Poulain D, Bossuyt X, Rutgeerts P; Belgian Group of Infliximab Expanded Access Program in Crohn's Disease. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1458-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094865&dopt=Abstract

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Seropositive rheumatoid arthritis associated with Crohn's disease. Author(s): Georgiadis AN, Tzambouras N, Ioachim E, Tsianos EV, Agnantis N, Drosos AA. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 363-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846059&dopt=Abstract

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Seroreactivities against Saccharomyces cerevisiae and Mycobacterium avium subsp. paratuberculosis p35 and p36 antigens in Crohn's disease patients. Author(s): Shafran I, Piromalli C, Decker JW, Sandoval J, Naser SA, El-Zaatari FA. Source: Digestive Diseases and Sciences. 2002 September; 47(9): 2079-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353858&dopt=Abstract

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Serpiginous choroidopathy: an unusual association with Crohn's disease. Author(s): Ugarte M, Wearne IM. Source: Clinical & Experimental Ophthalmology. 2002 December; 30(6): 437-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427238&dopt=Abstract

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Serum angiotensin I-converting enzyme is reduced in Crohn's disease and ulcerative colitis irrespective of genotype. Author(s): Matsuda T, Suzuki J, Furuya K, Masutani M, Kawakami Y. Source: The American Journal of Gastroenterology. 2001 September; 96(9): 2705-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569699&dopt=Abstract

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Serum measurements of pancreatitis associated protein in active Crohn's disease with ileal location. Author(s): Desjeux A, Barthet M, Barthellemy S, Dagorn JC, Hastier P, Heresbach D, Bernard JP, Grimaud JC. Source: Gastroenterologie Clinique Et Biologique. 2002 January; 26(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11938036&dopt=Abstract

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Severe anaphylactic reaction to infliximab in pediatric patients with Crohn's disease. Author(s): Diamanti A, Castro M, Papadatou B, Ferretti F, Gambarara M. Source: The Journal of Pediatrics. 2002 May; 140(5): 636-7; Author Reply 637. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032538&dopt=Abstract

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Severe gastroduodenal Crohn's disease: surgical treatment. Author(s): Salky B. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 129-30; Discussion 131. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769448&dopt=Abstract

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Severe lower gastrointestinal bleeding in Crohn's disease: successful control with infliximab. Author(s): Belaiche J, Louis E. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492221&dopt=Abstract

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Severe pneumococcal pneumonia following treatment with infliximab for Crohn's disease. Author(s): Ritz MA, Jost R. Source: Inflammatory Bowel Diseases. 2001 November; 7(4): 327. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720324&dopt=Abstract

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Severe polyneuropathy complicating active Crohn's disease: rapid response to Infliximab. Author(s): Rodino S, Sacca N, D'Amico T, Fragomeni A, Giglio A. Source: Gut. 2003 July; 52(7): 1070. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801971&dopt=Abstract

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Shortcoming in the diagnosis of TPMT deficiency in a patient with Crohn's disease using phenotyping only. Author(s): Schwab M, Schaeffeler E, Marx C, Zanger U, Aulitzky W, Eichelbaum M. Source: Gastroenterology. 2001 August; 121(2): 498-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11487563&dopt=Abstract

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Side-to-side isoperistaltic strictureplasty in the treatment of diffuse Crohn's disease. Author(s): Sommariva A, Ruffolo C. Source: Diseases of the Colon and Rectum. 2002 May; 45(5): 708. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004229&dopt=Abstract

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Sigmoidoscopically induced pneumatosis cystoides coli in Crohn's disease manifested by collar subcutaneous emphysema. Author(s): Gosi G, Huoranszki F. Source: Endoscopy. 2001 March; 33(3): 293. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293770&dopt=Abstract

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Simultaneous anus and bowel operation is preferable for anal fistula in Crohn's disease. Author(s): Shinozaki M, Koganei K, Fukushima T. Source: Journal of Gastroenterology. 2002; 37(8): 611-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203076&dopt=Abstract

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Small bowel adenocarcinoma presenting as a first manifestation of Crohn's disease: report of a case, and a literature review. Author(s): Christodoulou D, Skopelitou AS, Katsanos KH, Katsios C, Agnantis N, Price A, Kappas A, Tsianos EV. Source: European Journal of Gastroenterology & Hepatology. 2002 July; 14(7): 805-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169995&dopt=Abstract

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Small-area variations and sociodemographic correlates for the incidence of Crohn's disease and ulcerative colitis. Author(s): Blanchard JF, Bernstein CN, Wajda A, Rawsthorne P. Source: American Journal of Epidemiology. 2001 August 15; 154(4): 328-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495856&dopt=Abstract

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Smoking cessation and the course of Crohn's disease: an intervention study. Author(s): Cosnes J, Beaugerie L, Carbonnel F, Gendre JP. Source: Gastroenterology. 2001 April; 120(5): 1093-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11266373&dopt=Abstract

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Sonographic appearances of conglomerated polyps (giant polyposis) in patients with Crohn's disease. Author(s): de Barros N, Cerri GG, de Souza Rocha M, Goncalves MO. Source: Journal of Clinical Ultrasound : Jcu. 2000 May; 28(4): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751743&dopt=Abstract

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Specific seroreactivity of Crohn's disease patients against p35 and p36 antigens of M. avium subsp. paratuberculosis. Author(s): Naser SA, Hulten K, Shafran I, Graham DY, El-Zaatari FA. Source: Veterinary Microbiology. 2000 December 20; 77(3-4): 497-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11118734&dopt=Abstract

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Spontaneous free perforation of the small intestine in Crohn's disease. Author(s): Freeman HJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 January; 16(1): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11826334&dopt=Abstract

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Status of lipidsoluble antioxidants and TRAP in patients with Crohn's disease and healthy controls. Author(s): Genser D, Kang MH, Vogelsang H, Elmadfa I. Source: European Journal of Clinical Nutrition. 1999 September; 53(9): 675-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10509761&dopt=Abstract

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Steroid dependency in Crohn's disease. Author(s): Reinisch W, Vogelsang H. Source: Gastroenterology. 2002 July; 123(1): 393-5; Author Reply 395. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105883&dopt=Abstract

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Steroids for Crohn's disease--an appreciation and a vote of confidence. Author(s): Korelitz BI. Source: Inflammatory Bowel Diseases. 2002 May; 8(3): 219-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979144&dopt=Abstract

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Strategies in the prevention of post-operative recurrence in Crohn's disease. Author(s): Rutgeerts P. Source: Best Practice & Research. Clinical Gastroenterology. 2003 February; 17(1): 63-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617883&dopt=Abstract

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Strategies targeting tumor necrosis factor in Crohn's disease. Author(s): Sandborn WJ. Source: Acta Gastroenterol Belg. 2001 April-June; 64(2): 170-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475128&dopt=Abstract

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Strategy for surgical management of ileocolonic anastomotic recurrence in Crohn's disease. Author(s): Yamamoto T, Allan RN, Keighley MR. Source: World Journal of Surgery. 1999 October; 23(10): 1055-60; Discussion 1060-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512947&dopt=Abstract

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Strictureplasty for large bowel stenosis in Crohn's disease: quality of life after surgical therapy. Author(s): Broering DC, Eisenberger CF, Koch A, Bloechle C, Knoefel WT, Durig M, Raedler A, Izbicki JR. Source: International Journal of Colorectal Disease. 2001 April; 16(2): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11355323&dopt=Abstract

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Strictureplasty for short duodenal stenosis in Crohn's disease. Author(s): Takesue Y, Yokoyama T, Akagi S, Ohge H, Murakami Y, Imamura Y, Uemura K, Kanehiro T, Matsuura Y. Source: Journal of Gastroenterology. 2000 December; 35(12): 929-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573730&dopt=Abstract

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Strictureplasty in Crohn's disease: short- and long-term follow-up. Author(s): Laurent S, Detry O, Detroz B, DeRoover A, Joris J, Honore P, Louis E, Belaiche J, Jacquet N. Source: Acta Chir Belg. 2002 August; 102(4): 253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244904&dopt=Abstract

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Structural elucidation of a capsular polysaccharide from a clinical isolate of Bacteroides vulgatus from a patient with Crohn's disease. Author(s): Hashimoto M, Kirikae F, Dohi T, Kusumoto S, Suda Y, Kirikae T. Source: European Journal of Biochemistry / Febs. 2001 June; 268(11): 3139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389714&dopt=Abstract

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Structural study on lipid A and the O-specific polysaccharide of the lipopolysaccharide from a clinical isolate of Bacteroides vulgatus from a patient with Crohn's disease. Author(s): Hashimoto M, Kirikae F, Dohi T, Adachi S, Kusumoto S, Suda Y, Fujita T, Naoki H, Kirikae T. Source: European Journal of Biochemistry / Febs. 2002 August; 269(15): 3715-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153568&dopt=Abstract

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Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives? Author(s): Thjodleifsson B, Sigthorsson G, Cariglia N, Reynisdottir I, Gudbjartsson DF, Kristjansson K, Meddings JB, Gudnason V, Wandall JH, Andersen LP, Sherwood R, Kjeld M, Oddsson E, Gudjonsson H, Bjarnason I. Source: Gastroenterology. 2003 June; 124(7): 1728-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806605&dopt=Abstract

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Subtractive screening reveals up-regulation of NADPH oxidase expression in Crohn's disease intestinal macrophages. Author(s): Hausmann M, Spottl T, Andus T, Rothe G, Falk W, Scholmerich J, Herfarth H, Rogler G. Source: Clinical and Experimental Immunology. 2001 July; 125(1): 48-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11472425&dopt=Abstract

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Successful application of laparoscopic surgery to the treatment of Crohn's disease with fistulas. Author(s): Watanabe M, Hasegawa H, Yamamoto S, Hibi T, Kitajima M. Source: Diseases of the Colon and Rectum. 2002 August; 45(8): 1057-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195190&dopt=Abstract

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Successful desensitization and therapeutic use of infliximab in adult and pediatric Crohn's disease patients with prior anaphylactic reaction. Author(s): Puchner TC, Kugathasan S, Kelly KJ, Binion DG. Source: Inflammatory Bowel Diseases. 2001 February; 7(1): 34-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233658&dopt=Abstract

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Successful resection of a duodenal fistula complicated with recurrent Crohn's disease at the site of previous ileocolonic anastomosis: report of a case. Author(s): Nakagoe T, Sawai T, Tsuji T, Nanashima A, Shibasaki S, Yamaguchi H, Yasutake T. Source: Surgery Today. 2003; 33(7): 537-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507001&dopt=Abstract

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Successful treatment of refractory esophageal Crohn's disease with infliximab. Author(s): Fefferman DS, Shah SA, Alsahlil M, Gelrud A, Falchulk KR, Farrell RJ. Source: Digestive Diseases and Sciences. 2001 August; 46(8): 1733-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508675&dopt=Abstract

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Successful treatment with infliximab and methotrexate of pyostomatitis vegetans associated with Crohn's disease. Author(s): Bens G, Laharie D, Beylot-Barry M, Vergier B, Noblesse I, Beylot C, Amouretti M. Source: The British Journal of Dermatology. 2003 July; 149(1): 181-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890215&dopt=Abstract

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Surgery for Crohn's disease in Greece: a follow-up study of 79 cases. Author(s): Triantafillidis JK, Emmanouilidis A, Nicolakis D, Cheracakis P, Kogevinas M, Merikas E, Hereti I, Argyros N. Source: Hepatogastroenterology. 2001 July-August; 48(40): 1072-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490803&dopt=Abstract

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Surgical pathology of Crohn's disease. Author(s): Kleer CG, Appelman HD. Source: The Surgical Clinics of North America. 2001 February; 81(1): 13-30, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218160&dopt=Abstract

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Surviving too long in Crohn's disease. Author(s): Di Sabatino A, Corazza GR. Source: Gut. 2001 July; 49(1): 6-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413101&dopt=Abstract

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Sweet's syndrome in association with Crohn's disease. Author(s): Vaz A, Kramer K, Kalish RA. Source: Postgraduate Medical Journal. 2000 November; 76(901): 713-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060149&dopt=Abstract

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Sweet's syndrome in association with Crohn's disease: report of a case and review of the literature. Author(s): Rappaport A, Shaked M, Landau M, Dolev E. Source: Diseases of the Colon and Rectum. 2001 October; 44(10): 1526-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598485&dopt=Abstract

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Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease. Author(s): Cortot A, Colombel JF, Rutgeerts P, Lauritsen K, Malchow H, Hamling J, Winter T, Van Gossum A, Persson T, Pettersson E. Source: Gut. 2001 February; 48(2): 186-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156638&dopt=Abstract

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Systematic review and economic evaluation of the effectiveness of infliximab for the treatment of Crohn's disease. Author(s): Clark W, Raftery J, Song F, Barton P, Cummins C, Fry-Smith A, Burls A. Source: Health Technology Assessment (Winchester, England). 2003; 7(3): 1-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709295&dopt=Abstract

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Systemic cytomegalovirus infection with severe ileal bleeding associated with Crohn's disease. Author(s): Sekine Y, Yamamoto H, Miyata T, Iino S, Sunada F, Sugano K, Ishida A. Source: The American Journal of Gastroenterology. 2001 May; 96(5): 1653-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11374727&dopt=Abstract

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Tabulation of myeloid, lymphoid and intestinal malignancies in Crohn's disease. Author(s): Freeman HJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 November; 16(11): 779-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464971&dopt=Abstract

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Tacrolimus for the treatment of fistulas in patients with Crohn's disease: a randomized, placebo-controlled trial. Author(s): Sandborn WJ, Present DH, Isaacs KL, Wolf DC, Greenberg E, Hanauer SB, Feagan BG, Mayer L, Johnson T, Galanko J, Martin C, Sandler RS. Source: Gastroenterology. 2003 August; 125(2): 380-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891539&dopt=Abstract

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Taming the mucosal immune response in Crohn's disease. Author(s): van Deventer SJ. Source: Best Practice & Research. Clinical Gastroenterology. 2002 December; 16(6): 103543. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473306&dopt=Abstract

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Tc-99m HMPAO white blood cell SPECT of an enterovesical fistula complicating Crohn's disease. Author(s): Kim JH, Hyun IY, Kim YS, Woo ZH. Source: Clinical Nuclear Medicine. 2002 December; 27(12): 887-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607870&dopt=Abstract

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T-cell vaccination in Crohn's disease: principles and presentation of the first two cases. Author(s): Agnholt J, Kaltoft K, Jakobsen NO, Dahlerup JF. Source: Cytokines, Cellular & Molecular Therapy. 2002; 7(3): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850811&dopt=Abstract

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Th1-mediated intestinal inflammation in Crohn's disease may be induced by activation of lamina propria lymphocytes through synergistic stimulation of interleukin-12 and interleukin-18 without T cell receptor engagement. Author(s): Okazawa A, Kanai T, Watanabe M, Yamazaki M, Inoue N, Ikeda M, Kurimoto M, Ishii H, Hibi T. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3108-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492197&dopt=Abstract

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Thalidomide for the treatment of recalcitrant oral Crohn's disease and orofacial granulomatosis. Author(s): Hegarty A, Hodgson T, Porter S. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 May; 95(5): 576-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738949&dopt=Abstract

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Thalidomide in refractory vulvar ulcerations associated with Crohn's disease. Author(s): Kolivras A, De Maubeuge J, Andre J, Song M. Source: Dermatology (Basel, Switzerland). 2003; 206(4): 381-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771492&dopt=Abstract

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The -295T-to-C promoter polymorphism of the IL-16 gene is associated with Crohn's disease. Author(s): Glas J, Torok HP, Unterhuber H, Radlmayr M, Folwaczny C. Source: Clinical Immunology (Orlando, Fla.). 2003 March; 106(3): 197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706406&dopt=Abstract

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The 4G/4G genotype of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene is a determinant of penetrating behaviour in patients with Crohn's disease. Author(s): Sans M, Tassies D, Pellise M, Espinosa G, Quinto L, Pique JM, Reverter JC, Panes J. Source: Alimentary Pharmacology & Therapeutics. 2003 Apr15; 17(8): 1039-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694086&dopt=Abstract

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The c-insertion mutation of the NOD2 gene is associated with fistulizing and fibrostenotic phenotypes in Crohn's disease. Author(s): Radlmayr M, Torok HP, Martin K, Folwaczny C. Source: Gastroenterology. 2002 June; 122(7): 2091-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055616&dopt=Abstract

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The clinical course of fistulating Crohn's disease. Author(s): Bell SJ, Williams AB, Wiesel P, Wilkinson K, Cohen RC, Kamm MA. Source: Alimentary Pharmacology & Therapeutics. 2003 May 1; 17(9): 1145-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752351&dopt=Abstract

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The constitutive expression of galectin-3 is downregulated in the intestinal epithelia of Crohn's disease patients, and tumour necrosis factor alpha decreases the level of galectin-3-specific mRNA in HCT-8 cells. Author(s): Jensen-Jarolim E, Gscheidlinger R, Oberhuber G, Neuchrist C, Lucas T, Bises G, Radauer C, Willheim M, Scheiner O, Liu FT, Boltz-Nitulescu G. Source: European Journal of Gastroenterology & Hepatology. 2002 February; 14(2): 14552. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981338&dopt=Abstract

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The effectiveness of budesonide therapy for Crohn's disease. Author(s): Kane SV, Schoenfeld P, Sandborn WJ, Tremaine W, Hofer T, Feagan BG. Source: Alimentary Pharmacology & Therapeutics. 2002 August; 16(8): 1509-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182751&dopt=Abstract

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The epidermolysis bullosa acquisita antigen (type VII collagen) is present in human colon and patients with crohn's disease have autoantibodies to type VII collagen. Author(s): Chen M, O'Toole EA, Sanghavi J, Mahmud N, Kelleher D, Weir D, Fairley JA, Woodley DT. Source: The Journal of Investigative Dermatology. 2002 June; 118(6): 1059-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060403&dopt=Abstract

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The glucose breath test: a diagnostic test for small bowel stricture(s) in Crohn's disease. Author(s): Mishkin D, Boston FM, Blank D, Yalovsky M, Mishkin S. Source: Digestive Diseases and Sciences. 2002 March; 47(3): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911333&dopt=Abstract

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The mechanisms of prednisone inhibition of inflammation in Crohn's disease involve changes in intestinal permeability, mucosal TNFalpha production and nuclear factor kappa B expression. Author(s): Wild GE, Waschke KA, Bitton A, Thomson AB. Source: Alimentary Pharmacology & Therapeutics. 2003 August 1; 18(3): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895215&dopt=Abstract

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The molecular classification of the clinical manifestations of Crohn's disease. Author(s): Ahmad T, Armuzzi A, Bunce M, Mulcahy-Hawes K, Marshall SE, Orchard TR, Crawshaw J, Large O, de Silva A, Cook JT, Barnardo M, Cullen S, Welsh KI, Jewell DP. Source: Gastroenterology. 2002 April; 122(4): 854-66. Erratum In: Gastroenterology. 2003 July; 125(1): 281. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910336&dopt=Abstract

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The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Author(s): Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, Sandborn WJ. Source: Gastroenterology. 2002 April; 122(4): 875-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910338&dopt=Abstract

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The pathogenesis of Crohn's disease in the 21st century. Author(s): Hume G, Radford-Smith GL. Source: Pathology. 2002 December; 34(6): 561-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555995&dopt=Abstract

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The quality of life in patients with Crohn's disease. Author(s): Cohen RD. Source: Alimentary Pharmacology & Therapeutics. 2002 September; 16(9): 1603-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197839&dopt=Abstract

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The real cost of pediatric Crohn's disease: the role of infliximab in the treatment of pediatric IBD. Author(s): Kay M, Wyllie R. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 717-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738445&dopt=Abstract

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The relationship between heritability and smoking habits in Crohn's disease. Italian Cooperative Study Group. Author(s): Brignola C, Belloli C, Ardizzone S, Astegiano M, Cottone M, Trallori G. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095337&dopt=Abstract

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The role of endoscopy in the evaluation of fistulizing Crohn's disease. Author(s): Regueiro M. Source: Gastrointest Endosc Clin N Am. 2002 July; 12(3): 621-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486948&dopt=Abstract

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The role of enteral feeding in Crohn's disease of childhood. Author(s): Walker-Smith J. Source: Minerva Pediatr. 2000 May-June; 52(5-6): 277-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085053&dopt=Abstract

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The smoke is clearing in Crohn's disease. Author(s): Hanauer SB. Source: Current Gastroenterology Reports. 2001 December; 3(6): 456-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953718&dopt=Abstract

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The surgical management of Crohn's disease. Author(s): Schraut WH. Source: Gastroenterology Clinics of North America. 2002 March; 31(1): 255-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122736&dopt=Abstract

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The three most common CARD15 mutations associated with Crohn's disease and the chromosome 16 susceptibility locus for systemic lupus erythematosus. Author(s): Ferreiros-Vidal I, Garcia-Meijide J, Carreira P, Barros F, Carracedo A, GomezReino JJ, Gonzalez A. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 570-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649405&dopt=Abstract

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The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. Author(s): Neurath MF, Weigmann B, Finotto S, Glickman J, Nieuwenhuis E, Iijima H, Mizoguchi A, Mizoguchi E, Mudter J, Galle PR, Bhan A, Autschbach F, Sullivan BM, Szabo SJ, Glimcher LH, Blumberg RS. Source: The Journal of Experimental Medicine. 2002 May 6; 195(9): 1129-43. Erratum In: J Exp Med 2002 June 3; 195(11): 1513. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994418&dopt=Abstract

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The use of contrast-enhanced power Doppler ultrasound in the diagnosis and followup of inflammatory abdominal masses associated with Crohn's disease. Author(s): Sallomi DF. Source: European Journal of Gastroenterology & Hepatology. 2003 March; 15(3): 249-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610319&dopt=Abstract

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The vascularity of internal fistulae in Crohn's disease: an in vivo power Doppler ultrasonography assessment. Author(s): Maconi G, Sampietro GM, Russo A, Bollani S, Cristaldi M, Parente F, Dottorini F, Bianchi Porro G. Source: Gut. 2002 April; 50(4): 496-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889069&dopt=Abstract

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Therapeutic efficacy and safety of 6-mercaptopurine and azathioprine in patients with Crohn's disease. Author(s): Markowitz JF. Source: Reviews in Gastroenterological Disorders. 2003; 3 Suppl 1: S23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684586&dopt=Abstract

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Therapeutic inhibitors of tumor necrosis factor in Crohn's disease. Author(s): Ganesan S, Travis SP, Ahmad T, Jazrawi R. Source: Curr Opin Investig Drugs. 2002 September; 3(9): 1301-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498004&dopt=Abstract

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Therapeutic options in the management of strictures in Crohn's disease. Author(s): Legnani PE, Kornbluth A. Source: Gastrointest Endosc Clin N Am. 2002 July; 12(3): 589-603. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486946&dopt=Abstract

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Therapy of Crohn's disease in childhood. Author(s): Bremner AR, Beattie RM. Source: Expert Opinion on Pharmacotherapy. 2002 July; 3(7): 809-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083982&dopt=Abstract

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Therapy of osteoporosis in patients with Crohn's disease: a randomized study comparing sodium fluoride and ibandronate. Author(s): von Tirpitz C, Klaus J, Steinkamp M, Hofbauer LC, Kratzer W, Mason R, Boehm BO, Adler G, Reinshagen M. Source: Alimentary Pharmacology & Therapeutics. 2003 March 15; 17(6): 807-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641503&dopt=Abstract

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Thiopurine methyltransferase genotype distribution in patients with Crohn's disease. Author(s): Reuther LO, Sonne J, Larsen N, Dahlerup JF, Thomsen OO, Schmiegelow K. Source: Alimentary Pharmacology & Therapeutics. 2003 January; 17(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492733&dopt=Abstract

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Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine. Author(s): Bonaz B, Boitard J, Marteau P, Lemann M, Coffin B, Flourie B, Belaiche J, Cadiot G, Metman EH, Cortot A, Colombel JF; Getaid. Source: Alimentary Pharmacology & Therapeutics. 2003 August 15; 18(4): 401-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940925&dopt=Abstract

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TPMT in the treatment of Crohn's disease with azathioprine. Author(s): Lennard L. Source: Gut. 2002 August; 51(2): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117866&dopt=Abstract

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Treating Crohn's disease by inducing T lymphocyte apoptosis. Author(s): Van Den Brande JM, Peppelenbosch MP, Van Deventer SJ. Source: Annals of the New York Academy of Sciences. 2002 November; 973: 166-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485856&dopt=Abstract

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Treatment of active Crohn's disease with onercept (recombinant human soluble p55 tumour necrosis factor receptor): results of a randomized, open-label, pilot study. Author(s): Rutgeerts P, Lemmens L, Van Assche G, Noman M, Borghini-Fuhrer I, Goedkoop R. Source: Alimentary Pharmacology & Therapeutics. 2003 January; 17(2): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534402&dopt=Abstract

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Treatment of Crohn's disease with budesonide: this rose still has thorns! Author(s): Valentine JF. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 785-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003409&dopt=Abstract

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Treatment of Crohn's disease--the new era. Author(s): Jewell DP. Source: Dig Liver Dis. 2002 October; 34(10): 689-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469794&dopt=Abstract

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Treatment of fistulas in Crohn's disease with infliximab. Author(s): Lofberg R. Source: Gut. 1999 November; 45(5): 642-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517896&dopt=Abstract

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Treatment of perianal fistulizing Crohn's disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Author(s): Regueiro M, Mardini H. Source: Inflammatory Bowel Diseases. 2003 March; 9(2): 98-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769443&dopt=Abstract

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Treatment of severe Crohn's disease using antimycobacterial triple therapy-approaching a cure? Author(s): Borody TJ, Leis S, Warren EF, Surace R. Source: Dig Liver Dis. 2002 January; 34(1): 29-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926571&dopt=Abstract

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Treatment with drugs active against Mycobacterium avium subspecies paratuberculosis can heal Crohn's disease: more evidence for a neglected public health tragedy. Author(s): Hermon-Taylor J. Source: Dig Liver Dis. 2002 January; 34(1): 9-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926580&dopt=Abstract

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Tumor necrosis factor-receptor 2 is up-regulated on lamina propria T cells in Crohn's disease and promotes experimental colitis in vivo. Author(s): Holtmann MH, Douni E, Schutz M, Zeller G, Mudter J, Lehr HA, Gerspach J, Scheurich P, Galle PR, Kollias G, Neurath MF. Source: European Journal of Immunology. 2002 November; 32(11): 3142-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555659&dopt=Abstract

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Two large liver abscesses complicating Crohn's disease. Author(s): Kreuzpaintner G, Schmidt WU, West TB, Tischendorf FW. Source: Zeitschrift Fur Gastroenterologie. 2000 October; 38(10): 837-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089268&dopt=Abstract

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Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial. Author(s): Caprilli R, Cottone M, Tonelli F, Sturniolo G, Castiglione F, Annese V, Papi C, Viscido A, Camma C, Corrao G, Latella G. Source: Alimentary Pharmacology & Therapeutics. 2003 February 15; 17(4): 517-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622760&dopt=Abstract

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Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes. Author(s): Lawrance IC, Fiocchi C, Chakravarti S. Source: Human Molecular Genetics. 2001 March 1; 10(5): 445-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11181568&dopt=Abstract

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Ulcerative colitis is more strongly linked to chromosome 12 than Crohn's disease. Author(s): Parkes M, Satsangi J, Jewell DP, Weeks DE, Barmada MM, Duerr RH. Source: Gut. 2001 August; 49(2): 311. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476079&dopt=Abstract

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Ulcerative colon T-cell lymphoma: an unusual entity mimicking Crohn's disease and may be associated with fulminant hemophagocytosis. Author(s): Hsiao CH, Kao HL, Lin MC, Su IJ. Source: Hepatogastroenterology. 2002 July-August; 49(46): 950-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143251&dopt=Abstract

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Ulcerative duodenitis with ulcerative colitis: is it Crohn's disease or really ulcerative colitis? Author(s): Korelitz BI, Rajapakse R. Source: Journal of Clinical Gastroenterology. 2001 February; 32(2): 97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205662&dopt=Abstract

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Ultrasonographic findings in Crohn's disease. Author(s): Arienti V, Zamboni L, Gionchetti P, Rizzello F, Campieri M. Source: Gut. 2000 February; 46(2): 293. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712078&dopt=Abstract

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Ultrasound and magnetic resonance imaging assessmentof active bowel segments in Crohn's disease. Author(s): Miao YM, Koh DM, Amin Z, Healy JC, Chinn RJ, Zeegen R, Westaby D. Source: Clinical Radiology. 2002 October; 57(10): 913-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413916&dopt=Abstract

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Ultrasound and magnetic resonance imaging in Crohn's disease: a comparison. Author(s): Potthast S, Rieber A, Von Tirpitz C, Wruk D, Adler G, Brambs HJ. Source: European Radiology. 2002 June; 12(6): 1416-22. Epub 2001 December 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042948&dopt=Abstract

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Ultrasound in Crohn's disease of the small bowel. Author(s): Tarjan Z, Toth G, Gyorke T, Mester A, Karlinger K, Mako EK. Source: European Journal of Radiology. 2000 September; 35(3): 176-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11000560&dopt=Abstract

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Uncommon arthritis as presenting manifestation of silent Crohn's disease. Author(s): Garcia-Porrua C, Gonzalez-Gay MA, Gonzalez-Louzao C, Castro J, Rivas MJ, Santos E. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2000; 67(6): 553-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11195321&dopt=Abstract

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Unilateral retinal vasculitis, branch retinal artery occlusion and subsequent retinal neovascularization in Crohn's disease. Author(s): Saatci OA, Kocak N, Durak I, Ergin MH. Source: International Ophthalmology. 2001; 24(2): 89-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201349&dopt=Abstract

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Unusual development of hepatocellular carcinoma in a patient with Crohn's disease. Author(s): Borum ML. Source: Digestive Diseases and Sciences. 2001 October; 46(10): 2199-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680596&dopt=Abstract

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Update in medical treatment of Crohn's disease. Author(s): Regueiro MD. Source: Journal of Clinical Gastroenterology. 2000 December; 31(4): 282-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11129268&dopt=Abstract

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Updating the approach to Crohn's disease. Author(s): Hanauer SB. Source: Hosp Pract (Off Ed). 1999 August 15; 34(8): 77-8, 81-3, 87-93; Discussion 94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10459364&dopt=Abstract

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Up-regulation of the IL-12 receptor beta 2 chain in Crohn's disease. Author(s): Parrello T, Monteleone G, Cucchiara S, Monteleone I, Sebkova L, Doldo P, Luzza F, Pallone F. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 December 15; 165(12): 72349. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120856&dopt=Abstract

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Ureteroileal fistula: an unusual complication of Crohn's disease. Author(s): el Khader K, Karmouni T, Guille F, Lobel B. Source: Acta Gastroenterol Belg. 2000 July-September; 63(3): 312-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11190000&dopt=Abstract

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Urinary tract fistulas in Crohn's disease: surgery versus medical therapy. Author(s): Present DH. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2165-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358227&dopt=Abstract

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Use of antibiotics in the treatment of active Crohn's disease: experience with metronidazole and ciprofloxacin. Author(s): Prantera C, Berto E, Scribano ML, Falasco G. Source: Ital J Gastroenterol Hepatol. 1998 December; 30(6): 602-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10076781&dopt=Abstract

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Use of Doppler ultrasound in Crohn's disease. Author(s): Van Oostayen JA, Wasser MN. Source: Gut. 2000 July; 47(1): 156. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917753&dopt=Abstract

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Use of Doppler ultrasound of the SMA for Crohn's disease activity evaluation in clinical practice. Author(s): Van Oostayen JA, Wasser MJ. Source: Clinical Radiology. 2002 June; 57(6): 537. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138872&dopt=Abstract

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Use of Doppler ultrasound of the SMA for Crohn's disease activity evaluation in clinical practice. Author(s): Byrne MF, Murray FE, Lee MJ. Source: Clinical Radiology. 2002 June; 57(6): 537. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12069477&dopt=Abstract

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Use of infliximab in the treatment of Crohn's disease in children and adolescents. Author(s): Hyams JS. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 September; 33 Suppl 1: S36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685974&dopt=Abstract

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Use of infliximab in the treatment of Crohn's disease in children and adolescents. Author(s): Hyams JS, Markowitz J, Wyllie R. Source: The Journal of Pediatrics. 2000 August; 137(2): 192-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10931411&dopt=Abstract

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Use of short-term culture for identification of Mycobacterium avium subsp. paratuberculosis in tissue from Crohn's disease patients. Author(s): Schwartz D, Shafran I, Romero C, Piromalli C, Biggerstaff J, Naser N, Chamberlin W, Naser SA. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2000 June; 6(6): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11168138&dopt=Abstract

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Vaccines, Crohn's disease and autism. Author(s): Afzal MA, Minor PD. Source: Molecular Psychiatry. 2002; 7 Suppl 2: S49-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142950&dopt=Abstract

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Validation of a simplified clinical index to predict evolving patterns in Crohn's disease. Author(s): Nos P, Hinojosa J, Mora J, Garrigues V, Ponce J. Source: European Journal of Gastroenterology & Hepatology. 2002 August; 14(8): 847-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172404&dopt=Abstract

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Validation of the spanish version of the inflammatory bowel disease questionnaire on ulcerative colitis and Crohn's disease. Author(s): Lopez-Vivancos J, Casellas F, Badia X, Vilaseca J, Malagelada JR. Source: Digestion. 1999; 60(3): 274-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10343142&dopt=Abstract

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Variation at NOD2/CARD15 in familial and sporadic cases of Crohn's disease in the Ashkenazi Jewish population. Author(s): Zhou Z, Lin XY, Akolkar PN, Gulwani-Akolkar B, Levine J, Katz S, Silver J. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3095-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492195&dopt=Abstract

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Vascular endothelial growth factor (VEGF) in Crohn's disease: increased production by peripheral blood mononuclear cells and decreased VEGF165 labeling of peripheral CD14+ monocytes. Author(s): Griga T, Werner S, Koller M, Tromm A, May B. Source: Digestive Diseases and Sciences. 1999 June; 44(6): 1196-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389696&dopt=Abstract

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VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation. Author(s): Kanazawa S, Tsunoda T, Onuma E, Majima T, Kagiyama M, Kikuchi K. Source: The American Journal of Gastroenterology. 2001 March; 96(3): 822-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280558&dopt=Abstract

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Veno-occlusive disease (VOD) in Crohn's disease (CD) treated with azathioprine. Author(s): Holtmann M, Schreiner O, Kohler H, Denzer U, Neurath M, Galle PR, Hohler T. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1503-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924643&dopt=Abstract

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Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility. Author(s): Simmons JD, Mullighan C, Welsh KI, Jewell DP. Source: Gut. 2000 August; 47(2): 211-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896912&dopt=Abstract

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WAGR syndrome in a baby--the result of 6-MP treatment in a father affected by Crohn's disease? Author(s): Ben-Neriah Z, Ackerman Z. Source: The American Journal of Gastroenterology. 2001 January; 96(1): 251. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197266&dopt=Abstract

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Wegener's granulomatosis in a patient with Crohn's disease. Author(s): Codish S, Abu-Shakra M, Depsames R, Sion-Vardy N, Benharroch D, Sukenik S. Source: Isr Med Assoc J. 2000 August; 2(8): 630-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979362&dopt=Abstract

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Wernicke's encephalopathy in a patient with Crohn's disease: a pathological study. Author(s): Larnaout A, El-Euch G, Kchir N, Filali A, Hamida MB, Hentati F. Source: Journal of Neurology. 2001 January; 248(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11266021&dopt=Abstract

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What role, if any, for laparoscopic surgery in Crohn's disease of the hindgut? Author(s): Ignjatovic D, Bergamaschi R. Source: Acta Chir Iugosl. 2002; 49(2): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587460&dopt=Abstract

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Whole gut lavage fluid interleukin-1beta and interleukin-8 in smokers and nonsmokers with Crohn's disease in clinical remission. Author(s): Arnott ID, Williams N, Drummond HE, Ghosh S. Source: Dig Liver Dis. 2002 June; 34(6): 424-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132790&dopt=Abstract

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Wide-lumen stapled anastomosis vs. conventional end-to-end anastomosis in the treatment of Crohn's disease. Author(s): Munoz-Juarez M, Yamamoto T, Wolff BG, Keighley MR. Source: Diseases of the Colon and Rectum. 2001 January; 44(1): 20-5; Discussion 25-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805559&dopt=Abstract

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Wireless capsule video endoscopy is a superior diagnostic tool in comparison to barium follow-through and computerized tomography in patients with suspected Crohn's disease. Author(s): Eliakim R, Fischer D, Suissa A, Yassin K, Katz D, Guttman N, Migdal M. Source: European Journal of Gastroenterology & Hepatology. 2003 April; 15(4): 363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655255&dopt=Abstract

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Workforce composition and the sex ratio of Crohn's disease incidence. Author(s): Alic M. Source: The American Journal of Gastroenterology. 1999 December; 94(12): 3652-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606341&dopt=Abstract

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Yersinia enterocolitis mimicking Crohn's disease in a toddler. Author(s): Tuohy AM, O'Gorman M, Byington C, Reid B, Jackson WD. Source: Pediatrics. 1999 September; 104(3): E36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uid s=10469819&dopt=Abstract

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CHAPTER 2. NUTRITION AND CROHN’S DISEASE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Crohn’s disease.

Finding Nutrition Studies on Crohn’s Disease 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 “Crohn’s disease” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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The following is a typical result when searching for recently indexed consumer information on Crohn’s disease: •

Nutritional support in chronic inflammatory bowel disease. Source: Kirschner, B.S. Nutrition-and-the-M.D (USA). (February 1986). volume 12(2) page 1-2. digestive system diseases nutrition proteins calcium vitamins minerals additives fibre content 0732-0167 Summary: maladie de l' appareil digestif nutrition proteine calcium vitamine mineraux additif teneur en fibres

Additional consumer oriented references include: •

A new look at fish oil for treating Crohn's disease. Source: Tufts-University-diet-and-nutrition-letter (USA). (September 1996). volume 14(7) page 7. fish oils intestinal diseases supplements processing 0747-4105

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Crohn's disease and fiber. Source: Nutrition-and-the-M.D (USA). (February 1988). volume 14(2) page 1. fibre content therapeutic diets 0732-0167

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Crohn's disease. New drug may help when others fail. Source: Lewis, C FDA-Consum. 1999 Sep-October; 33(5): 26-9 0362-1332

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Metabolic bone disease and vitamin D deficiency in Crohn's disease. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. July 1983. volume 41 (7) page 213-216. 0029-6643

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Should enteral nutrition be considered as primary therapy in acute Crohn's disease? Author(s): University of Chicago, IL 60637. Source: Kushner, R F Nutr-Revolume 1992 June; 50(6): 166-9 0029-6643

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The relationship between habits of food consumption and reported reactions to food in people with inflammatory bowel disease--testing the limits. Author(s): School of Nursing, University of British Columbia, Vancouver, Canada. [email protected] Source: Joachim, G Nutr-Health. 1999; 13(2): 69-83 0260-1060

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

99Tcm-HMPAO leucocyte labelling in orofacial granulomatosis and gastrointestinal Crohn's disease in childhood and early adulthood. Author(s): University of Glasgow Dental School, UK. [email protected] Source: Gibson, J Neilly, J B Wray, A P Evans, T J MacKenzie, J R McKillop, J H NuclMed-Commun. 2000 February; 21(2): 155-8 0143-3636

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A case of Crohn's disease with recurrent massive life-threatening hemorrhage from terminal ileum. Author(s): Department of Medicine III, Osaka University Medical School, Suita City, Japan. Source: Egawa, T Kuroda, T Ogawa, H Takeda, A Kanazawa, S Harada, H Tomita, N Shimano, T Nakamura, H Hepatogastroenterology. 1999 May-June; 46(27): 1695-8 01726390

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A new look at fish oil for treating Crohn's disease. Source: Tufts-University-diet-and-nutrition-letter (USA). (September 1996). volume 14(7) page 7. fish oils intestinal diseases supplements processing 0747-4105

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Adrenal hemorrhage complicating ACTH therapy in Crohn's disease. Author(s): Department of Radiology, Babies Hospital, Columbia-Presbyterian Medical Center, New York, NY 10032. Source: Levin, T L Morton, E Pediatr-Radiol. 1993; 23(6): 457-8 0301-0449

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Advantages of laparoscopic resection for ileocolic Crohn's disease. Improved outcomes and reduced costs. Author(s): Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. [email protected] Source: Young Fadok, T M HallLong, K McConnell, E J Gomez Rey, G Cabanela, R L Surg-Endosc. 2001 May; 15(5): 450-4 1432-2218

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Alterations of the immune system in ulcerative colitis and Crohn's disease. Author(s): Department of Medicine, Washington University School of Medicine, Barnes Hospital, St. Louis, Missouri. Source: MacDermott, R P Stenson, W F Adv-Immunol. 1988; 42285-328 0065-2776

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An unusual cause of subocclusion in Crohn's disease. Author(s): Clinic of Digestive Surgery, Hopital Universitaire Brugmann, Brussels, Belgium. Source: Chahidi, N De Reuck, M Allee, J L Acta-Chir-Belg. 1995 Jan-February; 95(1): 52-4 0001-5458

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Anti-inflammatory effects of enteral diet components on Crohn's disease-affected tissues in vitro. Author(s): Department of Medical Sciences, University of Edinburgh, Western General Hospital, UK. Source: Meister, D Bode, J Shand, A Ghosh, S Dig-Liver-Dis. 2002 June; 34(6): 430-8 15908658

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Anti-TNF therapies have eliminated the need for steroids in pediatric Crohn's disease: pro. Why use steroids if safer therapies are available? Author(s): Center for Pediatric Inflammatory Bowel Disease, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104, USA. Source: Baldassano, R N Inflamm-Bowel-Dis. 2001 November; 7(4): 338-41; discussion 345-6 1078-0998

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Anti-TNF therapies in rheumatoid arthritis, Crohn's disease, sepsis, and myelodysplastic syndromes. Author(s): Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3515, [email protected] Source: Raza, A Microsc-Res-Tech. 2000 August 1; 50(3): 229-35 1059-910X

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Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease. Author(s): Second Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Japan. Source: Tsujikawa, T Satoh, J Uda, K Ihara, T Okamoto, T Araki, Y Sasaki, M Fujiyama, Y Bamba, T J-Gastroenterol. 2000; 35(2): 99-104 0944-1174

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Comparison of laparoscopically assisted and conventional ileocolic resection for Crohn's disease. Author(s): Department of Colorectal Surgery, Cleveland Clinic Florida, Fort Lauderdale 33309, USA. Source: Alabaz, O Iroatulam, A J Nessim, A Weiss, E G Nogueras, J J Wexner, S D Eur-JSurg. 2000 March; 166(3): 213-7 1102-4151

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Controlled trial comparing an elemental diet with prednisolone in the treatment of active Crohn's disease. Author(s): 1st Department of Internal Medicine, School of Medicine, Fukuoka University, Japan. Source: Okada, M Yao, T Yamamoto, T Takenaka, K Imamura, K Maeda, K Fujita, K Hepatogastroenterology. 1990 February; 37(1): 72-80 0172-6390

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Corticosteroid treatment in active Crohn's disease. Author(s): Service de gastroenterologie, CHU Sart Tilman, Liege. Source: Belaiche, J Louis, E Acta-Gastroenterol-Belg. 1998 Apr-June; 61(2): 153-7 00015644

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Corticosteroids for maintaining remission of Crohn's disease. Author(s): Department of Medicine, University of Toronto, Room 445, 600 University Avenue, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5. [email protected] Source: Steinhart, A H Ewe, K Griffiths, A M Modigliani, R Thomsen, O O CochraneDatabase-Syst-Revolume 2000; (2): CD000301 1469-493X

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Cost-effectiveness of magnetic resonance imaging and enteroclysis in the diagnostic imaging of Crohn's disease. Author(s): University of Ulm. Source: Ebinger, M Rieber, A Leidl, R Int-J-Technol-Assess-Health-Care. 2002 Summer; 18(3): 711-7 0266-4623

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Crohn's disease. New drug may help when others fail. Source: Lewis, C FDA-Consum. 1999 Sep-October; 33(5): 26-9 0362-1332

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Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction. Author(s): Inflammatory Bowel Disease Study Group, University College and Middlesex School of Medicine, United Kingdom. Source: Wakefield, A J Fox, J D Sawyerr, A M Taylor, J E Sweenie, C H Smith, M Emery, V C Hudson, M Tedder, R S Pounder, R E J-Med-Virol. 1992 November; 38(3): 183-90 0146-6615

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Diet and inflammatory bowel disease: a case-control study. Author(s): Department of Epidemiology, Karolinska Institutet, Stockholm, Sweden. Source: Persson, P G Ahlbom, A Hellers, G Epidemiology. 1992 January; 3(1): 47-52 1044-3983

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Effect of short-term topical corticosteroid treatment on mucosal enzyme systems in patients with distal inflammatory bowel disease. Author(s): Department of General Internal Medicine, University of Bonn, Germany. Source: Scheurlen, C Allgayer, H Hardt, M Kruis, W Hepatogastroenterology. 1998 SepOctober; 45(23): 1539-45 0172-6390

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Effects of elemental diet (ED) on surgical treatment in Crohn's disease. Author(s): Department of Surgery 2, Hyogo College of Medicine, Japan.

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Source: Ikeuchi, H Kusunoki, M Yanagi, H Yamamura, T Fukuda, Y Shimoyama, T Hepatogastroenterology. 2000 Mar-April; 47(32): 390-2 0172-6390 •

Efficacy of mycophenolate mofetil in patients failing 6-mercaptopurine or azathioprine therapy for Crohn's disease. Author(s): Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Source: Hassard, P V Vasiliauskas, E A Kam, L Y Targan, S R Abreu, M T InflammBowel-Dis. 2000 February; 6(1): 16-20 1078-0998

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Efficacy of oral adsorbent for treatment of peristomal fistula associated with Crohn's disease. Author(s): Second Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. Source: Tsujikawa, T Araki, Y Makino, J Uda, K Ihara, T Sasaki, M Fujiyama, Y Bamba, T J-Gastroenterol. 2000; 35(4): 296-8 0944-1174

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Elemental diets and Crohn's disease. Source: O'Morain, C Acta-Gastroenterol-Belg. 1987 Sep-October; 50(5): 574-8 0001-5644

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Enteral nutritional therapy for inducing remission of Crohn's disease (cochrane review). Author(s): GI/Nutrition, Clinical Epidemiology, Hospital for Sick Children, University of Toronto, 555 Universtiy Ave., Toronto, Ontario, CANADA, M5G 1X8. [email protected] Source: Zachos, M Tondeur, M Griffiths, A M Cochrane-Database-Syst-Revolume 2001; 3: CD000542 1469-493X

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Etiology and pathophysiology of inflammatory bowel disease--environmental factors. Author(s): Klinik und Poliklinik fur Innere Medizin I, Klinikum der Universitat, Regensburg, Germany. [email protected] Source: Andus, T Gross, V Hepatogastroenterology. 2000 Jan-February; 47(31): 29-43 0172-6390

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Evaluation of oral administration of folic and folinic acid to prevent folate deficiency in patients with inflammatory bowel disease treated with salicylazosulfapyridine. Author(s): First Medical Clinic, University of Bologna, Italy. Source: Pironi, L Cornia, G L Ursitti, M A Dallasta, M A Miniero, R Fasano, F Miglioli, M Barbara, L Int-J-Clin-Pharmacol-Res. 1988; 8(2): 143-8 0251-1649

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Functional defect of zinc transport in patients with Crohn's disease. Author(s): Department of Medicine, University of Erlangen-Nurnberg. Source: Stoll, R Schmidt, H Stern, H Ruppin, H Domschke, W Hepatogastroenterology. 1987 August; 34(4): 178-81 0172-6390

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

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Growth of an IBD controversy: growth hormone and Crohn's disease. Author(s): Department of Medicine, Medical College of Wisconsin, Milwaukee, USA. Source: Binion, D G Alemzadeh, R Inflamm-Bowel-Dis. 2001 May; 7(2): 176-8 1078-0998

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HLA-DR antigen expression in macroscopically uninvolved areas of intestinal epithelia in Crohn's disease. Author(s): First Department of Internal Medicine, Akita University School of Medicine, Japan.

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Source: Chiba, M Iizuka, M Horie, Y Igarashi, K Masamune, O Gastroenterol-Jpn. 1989 August; 24(4): 365-72 0435-1339 •

In favour of prophylactic treatment for post-operative recurrence in Crohn's disease. Author(s): Gastroenterology Unit, University of Rome La Sapienza, Rome, Italy. Source: Caprilli, R Taddei, G Viscido, A Ital-J-Gastroenterol-Hepatol. 1998 Apr; 30(2): 219-25 1125-8055

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In vitro cellular cytotoxicity in Crohn's disease and ulcerative colitis: relation with disease activity and treatment, and the effect of recombinant gamma-interferon. Author(s): Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands. Source: Aparicio Pages, M N Verspaget, H W Pena, A S Weterman, I T de Bruin, P A Mieremet Ooms, M A van der Zon, J M van Tol, E A Lamers, C B J-Clin-Lab-Immunol. 1989 July; 29(3): 119-24 0141-2760

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Increased sugar consumption in Japanese patients with Crohn's disease. Author(s): Second Dep. of Intern. Med., Facul. of Med., Kyushu University, Fukuoka, Japan. Source: Matsui, T Iida, M Fujishima, M Imai, K Yao, T Gastroenterol-Jpn. 1990 April; 25(2): 271 0435-1339

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Indications and options of nutritional treatment for Crohn's disease. A comparison of elemental and polymeric diets. Author(s): Department of Gastroenterology, Fukuoka University Chikushi Hospital, Japan. Source: Matsui, T Ueki, M Yamada, M Sakurai, T Yao, T J-Gastroenterol. 1995 November; 30 Suppl 895-7 0944-1174

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Inflammatory bowel disease in Japan: studies of epidemiology and etiopathogenesis. Author(s): First Department of Internal Medicine, Hirosaki University School of Medicine, Japan. Source: Yoshida, Y Murata, Y Med-Clin-North-Am. 1990 January; 74(1): 67-90 0025-7125

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Intravenous corticotrophin vs. hydrocortisone in the treatment of hospitalized patients with Crohn's disease: a randomized double-blind study and follow-up. Author(s): Department of Medicine, Lenox Hill Hospital, New York, New York 100211883, USA. Source: Chun, A Chadi, R M Korelitz, B I Colonna, T Felder, J B Jackson, M H Morgenstern, E H Rubin, S D Sacknoff, A G Gleim, G M Inflamm-Bowel-Dis. 1998 August; 4(3): 177-81 1078-0998

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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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Is fish oil (n-3 fatty acids) effective for the maintenance of remission in Crohn's disease? Source: Nakazawa, A Hibi, T J-Gastroenterol. 2000; 35(2): 173-5 0944-1174

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Is steroid dependent Crohn's disease a separate entity? Author(s): Division of Gastroenterology, Hospital Louis Mourier, Colombes, France. Source: Chochon, M Gaudebout, C Chagnon, J P Hay, J M Cerf, M Mater-Med-Pol. 1992 Jul-September; 24(3): 177-80 0025-5246

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Laparoscopically assisted intestinal resection in 88 patients with Crohn's disease. Author(s): Division of Laparoscopic Surgery, Department of Surgery, Mount Sinai Medical Center, 1010 Fifth Avenue, New York, NY 10029, USA. Source: Canin Endres, J Salky, B Gattorno, F Edye, M Surg-Endosc. 1999 June; 13(6): 5959 0930-2794

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Levels of zinc and thymulin in plasma from patients with Crohn's disease. Author(s): I.N.R.C.A. Res. Dept. Ctr. Immunol., Ancona, Italy. Source: Mocchegiani, E Brignola, C Iannone, P Campieri, M Pasquali, M Lanfranchi, G A Barbara, L Fabris, N Licastro, F J-Clin-Lab-Immunol. 1990 June; 32(2): 79-84 0141-2760

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Management of growth retardation in the young patient with Crohn's disease. Author(s): Department of Adult and Paediatric Gastroenterology, St Bartholomew's and the Royal London School of Medicine and Dentistry, Turner Street, London, E1 2AD, UK. [email protected] Source: Ballinger, Anne Expert-Opin-Pharmacother. 2002 January; 3(1): 1-7 1465-6566

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Managing Crohn's disease and ulcerative colitis. Author(s): St Thomas Hospital, London. Source: Evans, S Ciclitira, P J Practitioner. 1999 April; 243(1597): 307-14 0032-6518

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Medical management of Crohn's disease in childhood. Author(s): Department of Pediatrics, UCLA School of Medicine 90024. Source: Vargas, J H Semin-Pediatr-Surg. 1994 February; 3(1): 15-8 1055-8586

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Medical management of major internal fistulae in Crohn's disease. Author(s): Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. [email protected] Source: D'Haens, G Inflamm-Bowel-Dis. 2000 August; 6(3): 244-5 1078-0998

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Medical therapy in Crohn's disease. Author(s): Veterans Affairs Medical Center, Miami, FL 33125. Source: Rogers, A I Coelho Borges, S Postgrad-Med. 1992 December; 92(8): 169-73, 177-8, 183 passim 0032-5481

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Metabolism of vitamin A in inflammatory bowel disease. Author(s): Department of Gastroenterology and Metabolism, Medical Center of Postgraduate Education, Warsaw, Poland. Source: Janczewska, I Bartnik, W Butruk, E Tomecki, R Kazik, E Ostrowski, J Hepatogastroenterology. 1991 October; 38(5): 391-5 0172-6390

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Mitogenic response and interleukin 2 production in Crohn's disease. Author(s): Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan. Source: Miura, M Hiwatashi, N J-Clin-Lab-Immunol. 1987 November; 24(3): 113-6 01412760

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Multiplanar spiral CT enterography in patients with Crohn's disease using a negative oral contrast material: initial results of a noninvasive imaging approach. Author(s): Department of Radiology, Karl Franzens Medical School and University Hospital Graz, Auenbruggerplatz 9, 8036 Graz, Austria. Source: Reittner, P Goritschnig, T Petritsch, W Doerfler, O Preidler, K W Hinterleitner, T Szolar, D H Eur-Radiol. 2002 September; 12(9): 2253-7 0938-7994

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Natural, lectin- and phorbol ester-induced cellular cytotoxicity in Crohn's disease and ulcerative colitis. Author(s): Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands. Source: Aparicio Pages, M N Verspaget, H W Pena, A S Weterman, I T Mieremet Ooms, M A van der Zon, J M de Bruin, P A Lamers, C B J-Clin-Lab-Immunol. 1988 November; 27(3): 109-13 0141-2760

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New alternatives for the treatment of fistulas in Crohn's disease. Author(s): IInd Department of Internal Medicine University Hospital, Olomouc, Czech Republic. Source: Skvarilova, M Nicakova, R Axmann, K Acta-Univ-Palacki-Olomuc-Fac-Med. 1994; 13829-31 0301-2514

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Nutrition in Crohn's disease. Author(s): Numico Research, Wageningen, The Netherlands. [email protected] Source: Philipsen Geerling, B J Brummer, R J Curr-Opin-Clin-Nutr-Metab-Care. 2000 July; 3(4): 305-9 1363-1950

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Nutritional consequences and therapy in Crohn's disease. Source: Bingham, W W Gastroenterol-Nurs. 1990 Winter; 12(3): 189-92 1042-895X

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Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: effects on antioxidant status and fatty acid profile. Author(s): Department of Gastroenterology, University of Maastricht, The Netherlands. Source: Geerling, B J Badart Smook, A van Deursen, C van Houwelingen, A C Russel, M G Stockbrugger, R W Brummer, R J Inflamm-Bowel-Dis. 2000 May; 6(2): 77-84 1078-0998

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Nutritional therapy in Crohn's disease. Author(s): Department of Gastroenterology, Meath/Adelaide Hospital, Trinity College, Dublin, Ireland. Source: O'Sullivan, M A O'Morain, C A Inflamm-Bowel-Dis. 1998 February; 4(1): 45-53 1078-0998

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Oral nutritional supplementation is effective in the maintenance of remission in Crohn's disease. Author(s): Department of Gastroenterology, Hull Royal Infirmary, UK. Source: Verma, S Kirkwood, B Brown, S Giaffer, M H Dig-Liver-Dis. 2000 December; 32(9): 769-74

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Orthognathic surgery in patients with Crohn's disease: a review of the pathophysiology and perioperative management. Author(s): University of Pittsburgh Hospitals, PA. Source: Wilson, G W Sisto, J M J-Oral-Maxillofac-Surg. 1992 May; 50(5): 502-5 0278-2391

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Outcome of ileal pouch after secondary diagnosis of Crohn's disease. Author(s): Department of General and Thoracic Surgery, Centre Hospitalier Lyon-Sud, Pierre-Benite, France. Source: Peyregne, V Francois, Y Gilly, F N Descos, J L Flourie, B Vignal, J Int-JColorectal-Dis. 2000 February; 15(1): 49-53 0179-1958

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Pancytopenia associated with 5-aminosalicylic acid use in a patient with Crohn's disease. Author(s): First Department of Surgery, Akita University School of Medicine, Japan. Source: Kotanagi, H Ito, M Koyama, K Chiba, M J-Gastroenterol. 1998 August; 33(4): 571-4 0944-1174

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Peripheral and intestinal lymphocyte activation after in vitro exposure to cow's milk antigens in normal subjects and in patients with Crohn's disease. Author(s): Department of Gastroenterology 1st, University La Sapienza, Rome, Italy. Source: Biancone, L Paganelli, R Fais, S Squarcia, O D'Offizi, G Pallone, F Clin-ImmunolImmunopathol. 1987 December; 45(3): 491-8 0090-1229

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Prediction of treatment refractoriness in ulcerative colitis and Crohn's disease--do we have reliable markers? Author(s): Department of Internal Medicine I, University of Regensburg, Germany. Source: Gelbmann, C M Inflamm-Bowel-Dis. 2000 May; 6(2): 123-31 1078-0998

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Probiotics and Crohn's disease. Author(s): Division of Gastroenterology, S. Camillo-Forlanini Hospital, Rome, Italy. [email protected] Source: Prantera, C Scribano, M L Dig-Liver-Dis. 2002 September; 34 Suppl 2: S66-7 1590-8658

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Remission induced by a new specific oral polymeric diet in children with Crohn's disease. Author(s): Chelsea and Westminster Hospital, London, UK. Source: Fell, J M Paintin, M Donnet Hughes, A Arnaud Battandier, F MacDonald, T T Walker Smith, J A Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 1999; 2: 187-96; discussion 196-8 1422-7584

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Reversal of progressive nyctalopia in a patient with Crohn's disease. Author(s): Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, PQ. Source: Gans, M Taylor, C Can-J-Ophthalmol. 1990 April; 25(3): 156-8 0008-4182

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Role of prostaglandins on lymphocyte transformation in Crohn's disease. Author(s): Gastroenterology Unit, National Hospital Marques de Valdecilla, Faculty of Medicine, Santander, Spain. Source: Echevarria, S Cajigas, J Rodriguez de Lope, C Lozano, J L Pons Romero, F Allergol-Immunopathol-(Madr). 1989 Nov-December; 17(6): 317-21 0301-0546

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Severe muscle damage induced by high carbohydrate intake from elemental diet in a patient with Crohn's disease. Author(s): Department of Medicine, Kobe University School of Medicine, Japan. Source: Waki, S Kawanami, C Kanda, F Uenoyama, Y Maekawa, T Fukui, H Okada, A Matsushima, Y Kishi, K Kinoshita, Y Chiba, T J-Gastroenterol. 1998 February; 33(1): 1214 0944-1174

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Soluble interleukin-2 receptor and disease activity in Crohn's disease. Author(s): University of Edinburgh Department of Medicine, Royal Infirmary, UK. Source: Williams, A J Symons, J A Watchet, K Duff, G W J-Autoimmun. 1992 April; 5(2): 251-9 0896-8411

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Steroids for Crohn's disease--an appreciation and a vote of confidence. Author(s): Section of Gastroenterology, Lenox Hill Hospital, New York University School of Medicine, New York 10021, USA. Source: Korelitz, Burton I Inflamm-Bowel-Dis. 2002 May; 8(3): 219-22 1078-0998

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Surgical management and strategy in classical Crohn's disease. Author(s): Surgical Department II, University of Goteborg, Sweden. Source: Hulten, L Int-Surg. 1992 Jan-March; 77(1): 2-8 0020-8868

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Tc-99m-PEG-Liposomes for the evaluation of colitis in Crohn's disease. Author(s): Department of Nuclear Medicine, University Medical Center Nijmegen, The Netherlands. [email protected] Source: Brouwers, A H De Jong, D J Dams, E T Oyen, W J Boerman, O C Laverman, P Naber, T H Storm, G Corstens, F H J-Drug-Target. 2000; 8(4): 225-33 1061-186X

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The clinical entity of orofacial Crohn's disease. Author(s): Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. Source: Williams, A J Wray, D Ferguson, A Q-J-Med. 1991 May; 79(289): 451-8 0033-5622

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The diet of people with Crohn's disease. Source: Simcock, J Nurs-Stand. 1999 July 21-27; 13(44): 55 0029-6570

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The long-term results of resection and multiple resections in Crohn's disease. Author(s): Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104-4283, USA. Source: Krupnick, A S Morris, J B Semin-Gastrointest-Dis. 2000 January; 11(1): 41-51 1049-5118

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The relationship between habits of food consumption and reported reactions to food in people with inflammatory bowel disease--testing the limits. Author(s): School of Nursing, University of British Columbia, Vancouver, Canada. [email protected] Source: Joachim, G Nutr-Health. 1999; 13(2): 69-83 0260-1060

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The role of liquid diet in the management of small bowel Crohn's disease. Source: Korelitz, B I Inflamm-Bowel-Dis. 2000 February; 6(1): 66-7; discussion 68-9 10780998

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The role of the fecal stream in Crohn's disease: an historical and analytic review. Author(s): Department of Medicine, Mount Sinai Medical Center, New York, New York 10029, USA. Source: Janowitz, H D Croen, E C Sachar, D B Inflamm-Bowel-Dis. 1998 February; 4(1): 29-39 1078-0998

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Therapeutic efficacy of cyclic home elemental enteral alimentation in Crohn's disease: Japanese cooperative Crohn's disease study. Author(s): International Medical Center for Japan, Division of Gastroenterology, Tokyo, Japan. Source: Matsueda, K Shoda, R Takazoe, M Hiwatashi, N Bamba, T Kobayashi, K Saito, T Terano, A Yao, T J-Gastroenterol. 1995 November; 30 Suppl 891-4 0944-1174

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Therapeutic efficacy of elemental enteral alimentation in Crohn's disease. Author(s): Division of Gastroenterology, International Medical Center of Japan, Tokyo. Source: Matsueda, K J-Gastroenterol. 2000; 35 Suppl 1219 0944-1174

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Therapeutic efficacy of N-3 polyunsaturated fatty acid in experimental Crohn's disease. Author(s): Division of Gastroenterology, International Medical Center of Japan, Tokyo, Japan. Source: Shoda, R Matsueda, K Yamato, S Umeda, N J-Gastroenterol. 1995 November; 30 Suppl 898-101 0944-1174

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Therapy of Crohn's disease in childhood. Author(s): Paediatric Medical Unit, Southampton General Hospital, England. [email protected] Source: Beattie, R M Paediatr-Drugs. 2000 May-June; 2(3): 193-203 1174-5878

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Treatment of Crohn's disease. Author(s): Innere Medizin II, Universitatskliniken des Saarlandes, Homburg, Germany. [email protected] Source: Hoffmann, J C Zeitz, M Hepatogastroenterology. 2000 Jan-February; 47(31): 90100 0172-6390

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Use of Lactobacillus-GG in paediatric Crohn's disease. Author(s): Department of Paediatrics, University of Chicago, IL 60637, USA. [email protected] Source: Guandalini, S Dig-Liver-Dis. 2002 September; 34 Suppl 2: S63-5 1590-8658

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What is the association of primary sclerosing cholangitis with sex and inflammatory bowel disease in Turkish patients? Author(s): Department of Gastroenterology, School of Medicine, Hacettepe University, Ankara, Turkey. Source: Bayraktar, Y Arslan, S Saglam, F Uzunalimoglu, B Kayhan, B Hepatogastroenterology. 1998 Nov-December; 45(24): 2064-72 0172-6390

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Zinc deficiency in Crohn's disease. Source: Matsui, T J-Gastroenterol. 1998 December; 33(6): 924-5 0944-1174

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Zinc deficiency manifested by dermatitis and visual dysfunction in a patient with Crohn's disease. Author(s): Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Source: Myung, S J Yang, S K Jung, H Y Jung, S A Kang, G H Ha, H K Hong, W S Min, Y I J-Gastroenterol. 1998 December; 33(6): 876-9 0944-1174

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Zinc supplementation tightens “leaky gut” in Crohn's disease. Author(s): Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Universita di Padova, Italy. [email protected] Source: Sturniolo, G C Di Leo, V Ferronato, A D'Odorico, A D'Inca, R Inflamm-BowelDis. 2001 May; 7(2): 94-8 1078-0998

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to Crohn’s disease; 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 (some Web sites are subscription based): •

Vitamins Folic Acid Source: Healthnotes, Inc. www.healthnotes.com Folic Acid Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Folic acid Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Vitamin A Source: Healthnotes, Inc. www.healthnotes.com Vitamin A Source: Prima Communications, Inc.www.personalhealthzone.com

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Vitamin A Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin B Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B complex Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,962,00.html Vitamin B1 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B12 Source: Healthnotes, Inc. www.healthnotes.com Vitamin B9 (Folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin D Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,905,00.html Vitamin E Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com •

Minerals Biotin Source: Healthnotes, Inc. www.healthnotes.com

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Copper Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,886,00.html Folate Source: Integrative Medicine Communications; www.drkoop.com Folate Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc. www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Quercetin Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10053,00.html Zinc Source: Healthnotes, Inc. www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html Zinc/copper Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,938,00.html •

Food and Diet Wheat Source: Healthnotes, Inc. www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND CROHN’S DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Crohn’s disease. 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 Crohn’s disease 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 “Crohn’s disease” (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 Crohn’s disease: •

Altered healing following mucogingival surgery in a patient with Crohn's disease: a literature review and case report. Author(s): Andersen KM, Selvig KA, Leknes KN. Source: J Periodontol. 2003 April; 74(4): 537-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747460&dopt=Abstract

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Antioxidant vitamin supplementation in Crohn's disease decreases oxidative stress. a randomized controlled trial. Author(s): Aghdassi E, Wendland BE, Steinhart AH, Wolman SL, Jeejeebhoy K, Allard JP. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 348-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591053&dopt=Abstract

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Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease. Author(s): Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Van Assche G, Geboes K, Ceuppens JL, Rutgeerts P. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2000-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190167&dopt=Abstract

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Ascorbic acid absorption in Crohn's disease. Studies using L-[carboxyl-14C]ascorbic acid. Author(s): Pettit SH, Shaffer JL, Johns CW, Bennett RJ, Irving MH. Source: Digestive Diseases and Sciences. 1989 April; 34(4): 559-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2702887&dopt=Abstract

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Assessment of appropriate laboratory measurements to supplement the Crohn's disease activity index. Author(s): Andre C, Descos L, Landais P, Fermanian J. Source: Gut. 1981 July; 22(7): 571-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6973509&dopt=Abstract

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Augmented increase in tight junction permeability by luminal stimuli in the noninflamed ileum of Crohn's disease. Author(s): Soderholm JD, Olaison G, Peterson KH, Franzen LE, Lindmark T, Wiren M, Tagesson C, Sjodahl R. Source: Gut. 2002 March; 50(3): 307-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839706&dopt=Abstract

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Clinical experience of zinc supplementation during intravenous nutrition in Crohn's disease: value of serum and urine zinc measurements. Author(s): Main AN, Hall MJ, Russell RI, Fell GS, Mills PR, Shenkin A. Source: Gut. 1982 November; 23(11): 984-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6813200&dopt=Abstract

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Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease. Author(s): Tsujikawa T, Satoh J, Uda K, Ihara T, Okamoto T, Araki Y, Sasaki M, Fujiyama Y, Bamba T. Source: Journal of Gastroenterology. 2000; 35(2): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10680664&dopt=Abstract

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Clinical nutrition: 6. Management of nutritional problems of patients with Crohn's disease. Author(s): Jeejeebhoy KN.

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Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 April 2; 166(7): 913-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949990&dopt=Abstract •

Consumption of refined carbohydrate by patients with Crohn's disease in Tel-AvivYafo. Author(s): Silkoff K, Hallak A, Yegena L, Rozen P, Mayberry JF, Rhodes J, Newcombe RG. Source: Postgraduate Medical Journal. 1980 December; 56(662): 842-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7267494&dopt=Abstract

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Could immunostimulant drugs be useful in apparently medically refractory Crohn's disease? Author(s): Nardone G, Budillon G. Source: Digestive Diseases and Sciences. 1994 March; 39(3): 661-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8131706&dopt=Abstract

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Crohn's disease: a defensin deficiency syndrome? Author(s): Fellermann K, Wehkamp J, Herrlinger KR, Stange EF. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 627-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840673&dopt=Abstract

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Crohn's disease: an overview. Author(s): Metcalf C. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2002 April 17; 16(31): 45-52; Quiz 54-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998242&dopt=Abstract

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Decreased responsiveness of platelets to a stable prostacyclin analogue in patients with Crohn's disease. Reversal by n-3 polyunsaturated fatty acids. Author(s): Jaschonek K, Clemens MR, Scheurlen M. Source: Thrombosis Research. 1991 September 15; 63(6): 667-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1723538&dopt=Abstract

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Destructive arthritis of the hip in a patient with Crohn's disease. Author(s): Tibbles AC, Mierau DR, Sibley J. Source: Journal of Manipulative and Physiological Therapeutics. 1993 NovemberDecember; 16(9): 601-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8133196&dopt=Abstract

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Dissolution of biliary duct stones without papillotomy in a patient with Billroth II resection and Crohn's disease. Author(s): Zillessen E, Louis B, Durr HC. Source: Endoscopy. 1984 May; 16(3): 122-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6428868&dopt=Abstract

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Effect of a vegetable-protein-rich polymeric diet treatment on body composition and energy metabolism in inactive Crohn's disease. Author(s): Capristo E, Mingrone G, Addolorato G, Greco AV, Gasbarrini G. Source: European Journal of Gastroenterology & Hepatology. 2000 January; 12(1): 5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656203&dopt=Abstract

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Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. Author(s): Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Source: The New England Journal of Medicine. 1996 June 13; 334(24): 1557-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8628335&dopt=Abstract

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Effect of intravenously infused eicosapentaenoic acid on the leukotriene generation in patients with active Crohn's disease. Author(s): Ikehata A, Hiwatashi N, Kinouchi Y, Yamazaki H, Kumagai Y, Ito K, Kayaba Y, Toyota T. Source: The American Journal of Clinical Nutrition. 1992 November; 56(5): 938-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1329484&dopt=Abstract

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Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. Author(s): Den Hond E, Hiele M, Peeters M, Ghoos Y, Rutgeerts P. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1999 January-February; 23(1): 7-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888411&dopt=Abstract

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Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients. Author(s): Belluzzi A, Brignola C, Campieri M, Camporesi EP, Gionchetti P, Rizzello F, Belloli C, De Simone G, Boschi S, Miglioli M, et al. Source: Digestive Diseases and Sciences. 1994 December; 39(12): 2589-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7995183&dopt=Abstract

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Endosonographic evidence of persistence of Crohn's disease-associated fistulas after infliximab treatment, irrespective of clinical response. Author(s): van Bodegraven AA, Sloots CE, Felt-Bersma RJ, Meuwissen SG.

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Source: Diseases of the Colon and Rectum. 2002 January; 45(1): 39-45; Discussion 45-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786762&dopt=Abstract •

Epidemiology of Crohn's Disease. Author(s): Sandler RS, Golden AL. Source: Journal of Clinical Gastroenterology. 1986 April; 8(2): 160-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3745850&dopt=Abstract

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Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease? Author(s): Soderholm JD, Peterson KH, Olaison G, Franzen LE, Westrom B, Magnusson KE, Sjodahl R. Source: Gastroenterology. 1999 July; 117(1): 65-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10381911&dopt=Abstract

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Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn's disease: results of a double blind randomised multicentre European trial. Author(s): Gassull MA, Fernandez-Banares F, Cabre E, Papo M, Giaffer MH, SanchezLombrana JL, Richart C, Malchow H, Gonzalez-Huix F, Esteve M; Eurpoean Group on Enteral Nutrition in Crohn's Disease. Source: Gut. 2002 August; 51(2): 164-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117873&dopt=Abstract

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First experience with intracytoplasmic sperm injection for extreme oligozoospermia associated with Crohn's disease and 6-mercaptopurine chemotherapy. Author(s): Sills ES, Tucker MJ. Source: Asian Journal of Andrology. 2003 March; 5(1): 76-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647009&dopt=Abstract

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Glutamine supplementation and intestinal permeability in Crohn's disease. Author(s): Akobeng AK, Miller V, Thomas AG, Richmond K. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 May-June; 24(3): 196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850950&dopt=Abstract

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Green tea for remission maintenance in Crohn's disease? Author(s): Alic M. Source: The American Journal of Gastroenterology. 1999 June; 94(6): 1710-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364058&dopt=Abstract

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Hepatosplenic T-gammadelta lymphoma in a patient with Crohn's disease treated with azathioprine. Author(s): Navarro JT, Ribera JM, Mate JL, Granada I, Junca J, Batlle M, Milla F, Feliu E.

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Source: Leukemia & Lymphoma. 2003 March; 44(3): 531-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688327&dopt=Abstract •

Humoral inhibition of neutrophil chemotaxis in Crohn's disease. Author(s): D'Amelio R, Pallone F, Le Moli S, Pontesilli O, Ricci R, Montano S, Rossi P. Source: Scandinavian Journal of Immunology. 1985 December; 22(6): 597-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3937224&dopt=Abstract

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Hyperbaric oxygen and perineal Crohn's disease: a follow-up. Author(s): Brady CE 3rd. Source: Gastroenterology. 1993 October; 105(4): 1264. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8405878&dopt=Abstract

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Hyperbaric oxygen for perianal Crohn's disease. Author(s): Lavy A, Weisz G, Adir Y, Ramon Y, Melamed Y, Eidelman S. Source: Journal of Clinical Gastroenterology. 1994 October; 19(3): 202-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7806829&dopt=Abstract

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Hyperbaric oxygen therapy for perineal Crohn's disease. Author(s): Noyer CM, Brandt LJ. Source: The American Journal of Gastroenterology. 1999 February; 94(2): 318-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10022622&dopt=Abstract

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Hyperbaric oxygen: a new alternative in the treatment of perianal Crohn's disease. Author(s): Sipahi AM, Damiao AO, de Sousa MM, Barbutti RC, Trivellato S, Esteves C, D'Agostino M, Laudanna AA. Source: Revista Do Hospital Das Clinicas. 1996 September-October; 51(5): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9216097&dopt=Abstract

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Hyperbaric oxygenation in severe perineal Crohn's disease. Author(s): Colombel JF, Mathieu D, Bouault JM, Lesage X, Zavadil P, Quandalle P, Cortot A. Source: Diseases of the Colon and Rectum. 1995 June; 38(6): 609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7774472&dopt=Abstract

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Hypnosis and the treatment of ulcerative colitis and Crohn's disease. Author(s): Schafer DW. Source: Am J Clin Hypn. 1997 October; 40(2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9385722&dopt=Abstract

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Hypnotherapy for crohn's disease. A promising complementary/alternative therapy. Author(s): Abela MB. Source: Integr. Med. 2000 March 21; 2(2): 127-131. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882886&dopt=Abstract

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Ileal and colonic fatty acid profiles in patients with active Crohn's disease. Author(s): Buhner S, Nagel E, Korber J, Vogelsang H, Linn T, Pichlmayr R. Source: Gut. 1994 October; 35(10): 1424-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7959199&dopt=Abstract

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Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Author(s): Irvine EJ, Marshall JK. Source: Gastroenterology. 2000 December; 119(6): 1740-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113095&dopt=Abstract

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Increased mucosal tumour necrosis factor alpha production in Crohn's disease can be downregulated ex vivo by probiotic bacteria. Author(s): Borruel N, Carol M, Casellas F, Antolin M, de Lara F, Espin E, Naval J, Guarner F, Malagelada JR. Source: Gut. 2002 November; 51(5): 659-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377803&dopt=Abstract

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Increased permeability of macroscopically normal small bowel in Crohn's disease. Author(s): Peeters M, Ghoos Y, Maes B, Hiele M, Geboes K, Vantrappen G, Rutgeerts P. Source: Digestive Diseases and Sciences. 1994 October; 39(10): 2170-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7924738&dopt=Abstract

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Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG. Author(s): Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Source: Gut. 2002 September; 51(3): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171964&dopt=Abstract

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Intestinal permeability in patients with Crohn's disease and their first-degree relatives. Author(s): Howden CW, Gillanders I, Morris AJ, Duncan A, Danesh B, Russell RI. Source: The American Journal of Gastroenterology. 1994 August; 89(8): 1175-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8053430&dopt=Abstract

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Intestinal permeability of 51Cr-labelled ethylenediaminetetraacetic acid in patients with Crohn's disease and their healthy relatives. Author(s): Ainsworth M, Eriksen J, Rasmussen JW, Schaffalitzky de Muckadell OB.

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Source: Scandinavian Journal of Gastroenterology. 1989 October; 24(8): 993-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2512633&dopt=Abstract •

Intestinal permeability to [51Cr]EDTA in children with Crohn's disease and celiac disease. Author(s): Turck D, Ythier H, Maquet E, Deveaux M, Marchandise X, Farriaux JP, Fontaine G. Source: Journal of Pediatric Gastroenterology and Nutrition. 1987 July-August; 6(4): 5357. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3123634&dopt=Abstract

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Is fish oil (n-3 fatty acids) effective for the maintenance of remission in Crohn's disease? Author(s): Nakazawa A, Hibi T. Source: Journal of Gastroenterology. 2000; 35(2): 173-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10680676&dopt=Abstract

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Is lactobacillus GG helpful in children with Crohn's disease? Results of a preliminary, open-label study. Author(s): Gupta P, Andrew H, Kirschner BS, Guandalini S. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 October; 31(4): 453-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045848&dopt=Abstract

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Keeping Crohn's disease quiet. Author(s): Hodgson HJ. Source: The New England Journal of Medicine. 1996 June 13; 334(24): 1599-1600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8628343&dopt=Abstract

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Low- and high-fat, peptide-based diets in adolescents with active Crohn's disease. Author(s): Siguel E. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1997 September-October; 21(5): 304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9323695&dopt=Abstract

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Modification of in vivo and in vitro TNF-alpha, IL-1, and IL-6 secretion by circulating monocytes during hyperbaric oxygen treatment in patients with perianal Crohn's disease. Author(s): Weisz G, Lavy A, Adir Y, Melamed Y, Rubin D, Eidelman S, Pollack S. Source: Journal of Clinical Immunology. 1997 March; 17(2): 154-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9083891&dopt=Abstract

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Modulation of intestinal immune system by dietary fat intake: relevance to Crohn's disease. Author(s): Miura S, Tsuzuki Y, Hokari R, Ishii H. Source: Journal of Gastroenterology and Hepatology. 1998 December; 13(12): 1183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9918423&dopt=Abstract

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Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease. Author(s): Reimund JM, Wittersheim C, Dumont S, Muller CD, Baumann R, Poindron P, Duclos B. Source: Journal of Clinical Immunology. 1996 May; 16(3): 144-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8734357&dopt=Abstract

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Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: effects on antioxidant status and fatty acid profile. Author(s): Geerling BJ, Badart-Smook A, van Deursen C, van Houwelingen AC, Russel MG, Stockbrugger RW, Brummer RJ. Source: Inflammatory Bowel Diseases. 2000 May; 6(2): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833065&dopt=Abstract

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Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group). Author(s): Lorenz-Meyer H, Bauer P, Nicolay C, Schulz B, Purrmann J, Fleig WE, Scheurlen C, Koop I, Pudel V, Carr L. Source: Scandinavian Journal of Gastroenterology. 1996 August; 31(8): 778-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8858747&dopt=Abstract

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Polyneuropathy: an unusual extraintestinal manifestation of Crohn's disease. Author(s): Humbert P, Monnier G, Billerey C, Birgen C, Dupond JL. Source: Acta Neurologica Scandinavica. 1989 October; 80(4): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2554634&dopt=Abstract

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Prevention of bone mineral loss in patients with Crohn's disease by long-term oral vitamin D supplementation. Author(s): Vogelsang H, Ferenci P, Resch H, Kiss A, Gangl A. Source: European Journal of Gastroenterology & Hepatology. 1995 July; 7(7): 609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8590154&dopt=Abstract

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Probiotics and Crohn's disease. Author(s): Prantera C, Scribano ML.

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Source: Dig Liver Dis. 2002 September; 34 Suppl 2: S66-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408444&dopt=Abstract •

Probiotics in Crohn's disease. Author(s): Guslandi M. Source: Gut. 2001 December; 49(6): 873-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758503&dopt=Abstract

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Protagonist. Mycobacterium avium subspecies paratuberculosis is a cause of Crohn's disease. Author(s): Hermon-Taylor J. Source: Gut. 2001 December; 49(6): 755-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709506&dopt=Abstract

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Psychosocial aspects of Crohn's disease. Author(s): Ringel Y, Drossman DA. Source: The Surgical Clinics of North America. 2001 February; 81(1): 231-52, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218167&dopt=Abstract

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Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU). Author(s): Fernandez-Banares F, Hinojosa J, Sanchez-Lombrana JL, Navarro E, Martinez-Salmeron JF, Garcia-Puges A, Gonzalez-Huix F, Riera J, Gonzalez-Lara V, Dominguez-Abascal F, Gine JJ, Moles J, Gomollon F, Gassull MA. Source: The American Journal of Gastroenterology. 1999 February; 94(2): 427-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10022641&dopt=Abstract

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Rapid improvement in dermatitis after zinc supplementation in a patient with Crohn's disease. Author(s): Heimburger DC, Tamura T, Marks RD. Source: The American Journal of Medicine. 1990 January; 88(1): 71-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2294768&dopt=Abstract

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Rectal electrolyte transport and mucosal permeability in ulcerative colitis and Crohn's disease. Author(s): Rask-Madsen J, Hammersgaard EA, Knudsen E. Source: The Journal of Laboratory and Clinical Medicine. 1973 March; 81(3): 342-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4631401&dopt=Abstract

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Relationship between intestinal permeability to [51Cr]EDTA and inflammatory activity in asymptomatic patients with Crohn's disease.

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Author(s): Pironi L, Miglioli M, Ruggeri E, Levorato M, Dallasta MA, Corbelli C, Nibali MG, Barbara L. Source: Digestive Diseases and Sciences. 1990 May; 35(5): 582-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1691967&dopt=Abstract •

Review article: Crohn's disease--the role of nutritional therapy. Author(s): Forbes A. Source: Alimentary Pharmacology & Therapeutics. 2002 July; 16 Suppl 4: 48-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047260&dopt=Abstract

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Review article: prevention of postsurgical relapse and recurrence in Crohn's disease. Author(s): Cottone M, Orlando A, Viscido A, Calabrese E, Camma C, Casa A. Source: Alimentary Pharmacology & Therapeutics. 2003 June; 17 Suppl 2: 38-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786611&dopt=Abstract

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Saccharomyces boulardii in maintenance treatment of Crohn's disease. Author(s): Guslandi M, Mezzi G, Sorghi M, Testoni PA. Source: Digestive Diseases and Sciences. 2000 July; 45(7): 1462-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961730&dopt=Abstract

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Scleromalacia perforans associated with Crohn's disease. Treated with sodium versenate (EDTA). Author(s): Evans PJ, Eustace P. Source: The British Journal of Ophthalmology. 1973 May; 57(5): 330-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4197476&dopt=Abstract

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Selenium deficiency in a patient with Crohn's disease receiving long-term total parenteral nutrition. Author(s): Ishida T, Himeno K, Torigoe Y, Inoue M, Wakisaka O, Tabuki T, Ono H, Honda K, Mori T, Seike M, Yoshimatsu H, Sakata T. Source: Intern Med. 2003 February; 42(2): 154-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636234&dopt=Abstract

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Serum n3 polyunsaturated fatty acids are depleted in Crohn's disease. Author(s): Kuroki F, Iida M, Matsumoto T, Aoyagi K, Kanamoto K, Fujishima M. Source: Digestive Diseases and Sciences. 1997 June; 42(6): 1137-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9201073&dopt=Abstract

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Short report: zinc sulphate supplementation corrects abnormal erythrocyte membrane long-chain fatty acid composition in patients with Crohn's disease. Author(s): Belluzzi A, Brignola C, Campieri M, Gionchetti P, Rizzello F, Boschi S, Cunanne S, Miglioli M, Barbara L.

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Source: Alimentary Pharmacology & Therapeutics. 1994 February; 8(1): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8186338&dopt=Abstract •

Short-term efficacy of enteral nutrition in the treatment of active Crohn's disease: a randomized, controlled trial comparing nutrient formulas. Author(s): Sakurai T, Matsui T, Yao T, Takagi Y, Hirai F, Aoyagi K, Okada M. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2002 March-April; 26(2): 98103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871742&dopt=Abstract

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Supplement of a Chitosan and ascorbic acid mixture for Crohn's disease. A pilot study. Author(s): Tsujikawa T, Kanauchi O, Andoh A, Saotome T, Sasaki M, Fujiyama Y, Bamba T. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 February; 19(2): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591545&dopt=Abstract

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Supporting patients with Crohn's disease. Author(s): Pullen M. Source: Nurs Times. 1998 September 30-October 6; 94(39): 63. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9832848&dopt=Abstract

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T cell-B cell regulation in the intestinal lamina propria in Crohn's disease. Author(s): Elson CO, Machelski E, Weiserbs DB. Source: Gastroenterology. 1985 August; 89(2): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2861139&dopt=Abstract

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The effect of dietary yeast on the activity of stable chronic Crohn's disease. Author(s): Barclay GR, McKenzie H, Pennington J, Parratt D, Pennington CR. Source: Scandinavian Journal of Gastroenterology. 1992; 27(3): 196-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1502481&dopt=Abstract

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The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease. Author(s): Teahon K, Smethurst P, Pearson M, Levi AJ, Bjarnason I. Source: Gastroenterology. 1991 July; 101(1): 84-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1904381&dopt=Abstract

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The patient with Crohn's disease. Author(s): Klonowski EI, Masoodi JE.

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Source: Rn. 1999 March; 62(3): 32-7; Quiz 38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10205563&dopt=Abstract •

The relation between daily stress and Crohn's disease. Author(s): Garrett VD, Brantley PJ, Jones GN, McKnight GT. Source: Journal of Behavioral Medicine. 1991 February; 14(1): 87-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2038047&dopt=Abstract

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Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn's disease with special respect to chronic diarrhea--a pilot study. Author(s): Plein K, Hotz J. Source: Zeitschrift Fur Gastroenterologie. 1993 February; 31(2): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8465554&dopt=Abstract

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Therapeutic efficacy of N-3 polyunsaturated fatty acid in experimental Crohn's disease. Author(s): Shoda R, Matsueda K, Yamato S, Umeda N. Source: Journal of Gastroenterology. 1995 November; 30 Suppl 8: 98-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8563904&dopt=Abstract

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Therapy of Crohn's disease in childhood. Author(s): Beattie RM. Source: Paediatric Drugs. 2000 May-June; 2(3): 193-203. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10937470&dopt=Abstract

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Unsatisfactory effect of cyclosporin A treatment in Crohn's disease: a report of five cases. Author(s): Lofberg R, Angelin B, Einarsson K, Gabrielsson N, Ost L. Source: Journal of Internal Medicine. 1989 September; 226(3): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2677208&dopt=Abstract

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Use of Lactobacillus-GG in paediatric Crohn's disease. Author(s): Guandalini S. Source: Dig Liver Dis. 2002 September; 34 Suppl 2: S63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408443&dopt=Abstract

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Whole body leucine metabolism in adolescents with Crohn's disease and growth failure during nutritional supplementation. Author(s): Motil KJ, Grand RJ, Matthews DE, Bier DM, Maletskos CJ, Young VR. Source: Gastroenterology. 1982 June; 82(6): 1359-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6802699&dopt=Abstract

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Zinc in mononuclear leucocytes in alcoholics with liver cirrhosis or chronic pancreatitis and in patients with Crohn's disease before and after zinc supplementation. Author(s): Bro S, Stokholm M, Jorgensen PJ. Source: J Trace Elem Electrolytes Health Dis. 1989 December; 3(4): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2535348&dopt=Abstract

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Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease. Author(s): Brignola C, Belloli C, De Simone G, Evangelisti A, Parente R, Mancini R, Iannone P, Mocheggiani E, Fabris N, Morini MC, et al. Source: Alimentary Pharmacology & Therapeutics. 1993 June; 7(3): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8364132&dopt=Abstract

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Zinc supplementation tightens “leaky gut” in Crohn's disease. Author(s): Sturniolo GC, Di Leo V, Ferronato A, D'Odorico A, D'Inca R. Source: Inflammatory Bowel Diseases. 2001 May; 7(2): 94-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383597&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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The following is a specific Web list relating to Crohn’s disease; 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 (some Web sites are subscription based): •

General Overview Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com Allergies and Sensitivities Source: Healthnotes, Inc. www.healthnotes.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc. www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Healthnotes, Inc. www.healthnotes.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Diarrhea Source: Healthnotes, Inc. www.healthnotes.com Diarrhea Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Integrative Medicine Communications; www.drkoop.com High Homocysteine Source: Healthnotes, Inc. www.healthnotes.com Inflammatory Bowel Disease Source: Healthnotes, Inc. www.healthnotes.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease, Crohn's Source: Integrative Medicine Communications; www.drkoop.com Irritable Bowel Syndrome Source: Healthnotes, Inc. www.healthnotes.com

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Malabsorption Source: Healthnotes, Inc. www.healthnotes.com Pancreatic Insufficiency Source: Healthnotes, Inc. www.healthnotes.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Rubella Source: Integrative Medicine Communications; www.drkoop.com Stomach Inflammation Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc. www.healthnotes.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com Vitamin B12 Deficiency Source: Healthnotes, Inc. www.healthnotes.com •

Alternative Therapy Colon therapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,682,00.html Homeopathy Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com

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Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Aloe Alternative names: Aloe vera, Aloe barbadensis Source: Healthnotes, Inc. www.healthnotes.com Aloe vera Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10001,00.html Arginine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10005,00.html Boswellia Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,759,00.html Cascara Alternative names: Cascara sagrada, Rhamnus purshiani cortex Source: Healthnotes, Inc. www.healthnotes.com Cascara sagrada Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10013,00.html 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 Comfrey Alternative names: Symphytum officinale Source: Healthnotes, Inc. www.healthnotes.com Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Cranesbill Alternative names: Geranium maculatum Source: Healthnotes, Inc. www.healthnotes.com

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Digestive Enzymes Source: Healthnotes, Inc. www.healthnotes.com Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com EPA Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc. www.healthnotes.com Green-Lipped Mussel Source: Healthnotes, Inc. www.healthnotes.com Guggul Alternative names: Commiphora mukul Source: Healthnotes, Inc. www.healthnotes.com Gugulipid Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10033,00.html Herbal digestive formula Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10104,00.html Horsetail Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10105,00.html Ispaghula Source: Integrative Medicine Communications; www.drkoop.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc. www.healthnotes.com

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Licorice Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Lipase Source: Healthnotes, Inc. www.healthnotes.com Marshmallow Alternative names: Althea officinalis Source: Healthnotes, Inc. www.healthnotes.com Marshmallow Source: Prima Communications, Inc.www.personalhealthzone.com Mesalamine Source: Healthnotes, Inc. www.healthnotes.com Oak Alternative names: Quercus spp. Source: Healthnotes, Inc. www.healthnotes.com Oral Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Plantago isphagula Source: Integrative Medicine Communications; www.drkoop.com Probiotics Source: Healthnotes, Inc. www.healthnotes.com Psyllium Alternative names: Ispaghula,Plantago isphagula Source: Integrative Medicine Communications; www.drkoop.com Senna Alternative names: Cassia senna, Cassia angustifolia Source: Healthnotes, Inc. www.healthnotes.com Slippery Elm Alternative names: Ulmus rubra, Ulmus fulva Source: Healthnotes, Inc. www.healthnotes.com Slippery Elm Source: Prima Communications, Inc.www.personalhealthzone.com Slippery elm Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10056,00.html

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Sulfasalazine Source: Healthnotes, Inc. www.healthnotes.com Witch Hazel Alternative names: Hamamelis virginiana Source: Healthnotes, Inc. www.healthnotes.com Yarrow Alternative names: Achillea millefolium 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 CROHN’S DISEASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to Crohn’s disease. 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 “Crohn’s disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Crohn’s disease, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Crohn’s Disease 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 Crohn’s disease. 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: •

Bacteria and Galphai2: Host-pathogen Interactions in Inflammatory Bowel Disease by Dalwadi, Harnisha Nagin; Phd from University of California, Los Angeles, 2002, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3045582

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Followup Study of Inflammatory Bowel Disease: Effect of Stress and Biological Markers by Duffy, Linda Claire, Phd from State University of New York at Buffalo, 1987, 303 pages http://wwwlib.umi.com/dissertations/fullcit/8718533

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Formulation Development and In-vitro Evaluation of a Polysaccharide-based Colonspecific Drug Delivery System (csdds) for the Treatment of Inflammatory Bowel Disease by Singh, Brahma N. Phd from St. John's University (new York), School of Pharmacy, 2003, 191 pages http://wwwlib.umi.com/dissertations/fullcit/3080556

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Genetic Studies in Inflammatory Bowel Disease by Silverberg, Mark Steven; Phd from University of Toronto (canada), 2002, 203 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74736

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Inflammatory Bowel Disease As a Cultural Artifact: an Ethnography of the Politics of Suffering by Foulds, John Simon, Phd from The University of British Columbia (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/f1933605

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Oxidative Stress Regulation of Intestinal Smooth Muscle Il-8 in Crohn's Disease by Alzzoghaibi, Mohammad Abdullah; Phd from Virginia Commonwealth University, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3055300

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Pharmacokinetic and Drug Interaction Studies on Metronidazole in Crohn's Disease by Eradiri, Okponanabofa; Phd from University of Alberta (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL41045

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Women Living with Crohn's Disease by Compton, M. Lynne; Msc from University of Windsor (canada), 2002, 76 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75779

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 CROHN’S DISEASE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Crohn’s disease.

Recent Trials on Crohn’s Disease The following is a list of recent trials dedicated to Crohn’s disease.8 Further information on a trial is available at the Web site indicated. •

A pharmacokinetic study to determine the oral bioavailability of methotrexate in patients with inflammatory bowel disease Condition(s): Inflammatory Bowel Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Crohn's and Colitis Foundation Purpose - Excerpt: Patients with inflammatory bowel disease (IBD) who require methotrexate (MTX)for treatment currently receive this drug by injection. MTX is also available as a pill that can be given by mouth but it is not known how well the drug enters the body in patients with Crohn’s disease or ulcerative colitis. This study is being done to compare how much MTX enters the body when the drug is taken by mouth compared to when it is given by injection. If the drug is well absorbed, it may allow patients to receive the drug by mouth. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035074

•

A Phase II Study of CP-461 for the Treatment of Crohn's Disease Condition(s): Crohn's Disease

8

These are listed at www.ClinicalTrials.gov.

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Study Status: This study is currently recruiting patients. Sponsor(s): Cell Pathways Purpose - Excerpt: Patients with moderately to severely active Crohn's disease will be treated with oral CP-461 200 mg (2 x 100 mg capsules) twice-daily for 8 weeks. The purpose of this study is to see if CP-461 improves the symptoms of Crohn's disease and/or the patient's quality of life. Patient's safety will be monitored throughout the study. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042055 •

A Phase II Study of the Human Anti-TNF Antibody Adalimumab for the Induction of Clinical Remission in Subjects with Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Abbott Laboratories Purpose - Excerpt: Purpose of the study is to test whether adalimumab can induce clinical remission in subjects with active Crohn's disease when compared to placebo (an inactive substance) Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055523

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A Randomized Trial of Rosiglitazone for Ulcerative Colitis Condition(s): Ulcerative Colitis; Inflammatory Bowel Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); GlaxoSmithKline Purpose - Excerpt: This is a multicenter, randomized, double-blind, placebo-controlled study evaluating rosiglitazone: 4 mg tablets or placebo tablets administered orally twice daily for 12 weeks. The purpose of the study is to evaluate the efficacy and safety of rosiglitazone in the treatment of mild to moderately active ulcerative colitis. Disease activity will be measured using a standard disease activity index. Calculation of the index requires patients to undergo flexible sigmoidoscopy at the start of the study and at week 12. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065065

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Active Crohn's Disease Study Condition(s): Crohn Disease Study Status: This study is currently recruiting patients. Sponsor(s): Wyeth-Ayerst Research Purpose - Excerpt: To assess the activity of multiple doses of oral rhIL-11 in patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] score from 220-400). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040521

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Alicaforsen (ISIS 2302) in Patients with Active Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals Purpose - Excerpt: ISIS 2302 is an antisense oligonucleotide drug that reduces the production of a specific protein called intercellular adhesion molecule (ICAM-1), a substance that plays a significant role in the increase of inflammation. People with Crohn's disease have been shown to over-produce ICAM-1 in their gut tissues. Alicaforsen works by blocking ICAM-1 messenger RNA, the "instruction" molecule that is required for the production of ICAM-1 protein. This trial will examine effects of alicaforsen delivered by 2-hour intravenous infusion over a four-week period, compared to a placebo. Patients may remain on stable background 5-ASA, antibiotic, or immunosuppressive drugs, and prednisone (or equivalent) at
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Alicaforsen (ISIS 2302) in Patients with Active Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals Purpose - Excerpt: ISIS 2302 is an antisense oligonucleotide drug that reduces the production of a specific protein called intercellular adhesion molecule (ICAM-1), a substance that plays a significant role in the increase of inflammation. People with Crohn's disease have been shown to over-produce ICAM-1 in their gut tissues. Alicaforsen works by blocking ICAM-1 messenger RNA, the "instruction" molecule that is required for the production of ICAM-1 protein. This trial will examine effects of alicaforsen delivered by 2-hour intravenous infusion over a four-week period, compared to a placebo. Patients may remain on stable background 5-ASA, antibiotic, or immunosuppressive drugs, and prednisone (or equivalent) at
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048295 •

Clotrimazole Enemas for Pouchitis in Children and Adults Condition(s): Ulcerative Colitis; Pouchitis; Ileitis; Inflammatory Bowel Disease Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: Colectomy with creation of an ileal pouch (IPAA) is now the treatment of choice for patients with ulcerative colitis that is resistant to existing medical therapies. The development of inflammation in these ileal reservoirs, a clinical entity referred to as pouchitis, is the most common long-term complication of this procedure and can affect 50-60% of adults and children. We have previously demonstrated that clotrimazole (delivered as a rectal suppository) is generally safe, effective, and displays poor systemic absorption when used in pediatric and adults with active pouchitis. We saw clinical benefit in patients with pouch disease that had previously failed to respond to standard antibiotic, steroid, or immunosuppressive therapies. The clinical trial outlined here will define the effectiveness and safety of topical clotrimazole therapy (delivered as a rectal enema) in pediatric (aged greater than two years) and adult patients with pouchitis. Subjects in this study will be randomly assigned to receive either placebo (no active drug, 4 subjects) or one of two clotrimazole therapy groups: 2500 mg/day (8 subjects) or 4000mg/day (8 subjects). No washout period is required, and subjects will be allowed to continue their existing anti-inflammatory medications during their participation in the study. Clotrimazole will be delivered nightly in the form of an enema. Subjects will undergo flexible sigmoidoscopy (pouchoscopy) prior to and again after completing one month of study therapy, and pouch disease activity will be graded at after each procedure using the Pouchitis Disease Activity Index (PDAI). Clinical improvement will be defined as a drop in PDAI score. If the drop in PDAI scores between placebo and either active clotrimazole treatment group is not significant, and no subject experiences what are determined to be study-related adverse effects, a second cohort of subjects will be recruited and studied after receiving one month of either placebo (4 subjects), 6000 mg/day clotrimazole (8 subjects), or 7500mg/day clotrimazole (8 subjects). Subjects will be assessed for adverse effects at the midpoint of the study. Clotrimazole blood levels will be measured during the first and last day of study participation. In addition, adults will complete a health related quality of life assessment at baseline and after completing study drug therapy. All subjects will be eligible for one month of open-label study drug therapy after completing one month of study drug therapy. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061282

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CNI-1493 for Treatment of Moderate to Severe Crohn's Disease Condition(s): Crohn Disease Study Status: This study is currently recruiting patients.

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Sponsor(s): Cytokine PharmaSciences Purpose - Excerpt: The purpose of this study is to determine whether CNI-1493 is safe and effective in the treatment of moderate to severe Crohn's Disease. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038766 •

Extracorporeal Photopheresis to Maintain Symptoms Remission During Steroid Withdrawal in Patients with Steroid-Dependent Crohn's Disease Condition(s): Crohn Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the safety and effectiveness of extracorporeal photopheresis (ECP) in controlling Crohn's disease symptoms as patients taper their corticosteroid dose. Crohn's disease is a chronic inflammatory bowel disease. Patients commonly have chronic diarrhea with abdominal pain, loss of appetite and weight loss. Acute disease flares are treated with large doses of corticosteroids, but long-term use of these drugs can have harmful side effects. ECP (described below), is approved to treat skin symptoms associated with a type of cancer called cutaneous T-cell lymphoma and has been used experimentally in conditions involving abnormal inflammation. Patients 18 years of age and older who have had Crohn's disease for at least 6 months, who are corticosteroid-dependent, and whose symptoms are controlled well enough so that their Crohn's Disease Activity Index (CDAI) is less than 220, may be eligible for this study. Candidates will be screened with a medical history and review of medical records, physical examination, electrocardiogram, blood tests, urine pregnancy test for women of childbearing potential, and a questionnaire about how Crohn's disease affects their life and activities. Patients with a CDAI score of less than 150 will begin ECP treatments as soon as possible. Those with scores from 150 to 219 will have their corticosteroid dose increased enough to bring their CDAI score to below 150 before beginning ECP. Patients who do not achieve a CDAI of less than 150 after 4 to 6 weeks of increased corticosteroids will be excluded from the study. Participants will have ECP treatments for 2 consecutive days every 2 weeks for 24 weeks, for a total of 26 treatments. For ECP, patients undergo leukapheresis, a method of collecting large numbers of white blood cells, or leukocytes-cells that may be responsible for many of the medical problems in Crohn's disease. Whole blood is collected through a needle in an arm vein, similar to donating a unit of blood. The blood flows through a machine that separates it into its components by spinning. The white cells are removed and collected in a plastic bag, and the red blood cells and plasma are returned to the patient's bloodstream through the same needle. The collected white cells are mixed with a drug called UVADEX(r) (Registered Trademark), exposed to ultraviolet (UVA) light, and then returned to the patients' bloodstream. (The UVADEX allows the blood cells to absorb more UVA.) The UVA changes the cells in a way that, once they are back in the body, they cause changes in other cells like them. Each ECP treatment takes 3 to 4 hours. On the first day of each 2-day treatment, patients will undergo a review of symptoms, check of vital signs, and blood draw. They will complete a CDAI diary for 7 days before the first of the two ECP treatments and a questionnaire about their life and activities at 4-week intervals. During the ECP treatment period, corticosteroids will be slowly reduced as long as disease

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symptoms do not worsen. Patients whose disease remains under control with cessation of all steroids may begin maintenance ECP, 2 days in a row every 4 weeks for an additional 20 weeks (another 10 treatments), with the same follow-up as described above, and a full physical examination 4 weeks after the final treatment. Patients who were able to reduce, but not stop, steroid treatment may be considered for maintenance therapy if it is thought that continuing treatment may enable further reduction of steroids. Patients whose disease symptoms worsen with ECP or who have not been able to decrease their steroid dose will not be eligible for maintenance therapy and their participation in the study will end. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056355 •

G-CSF to Treat Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the effectiveness of G-CSF in treating patients with Crohn's disease-a long-term recurring inflammation of the small and large intestine. Patients may have swelling and bleeding of the intestinal lining, which can lead to infection and abdominal pain, weight loss, fever, diarrhea, bloody stools, fistula (connections between the skin and intestine), intestinal blockages, and abscesses. Although there are various treatments for Crohn's disease, many patients continue to have inflammation that is difficult to control or severe side effects from the medications. G-CSF is an approved drug that is used to increase white blood cell counts. Other cells, immune cells, exposed to G-CSF can develop a specific immune action-a Th-2 responsethat decreases the inflammatory response in Crohn's disease-a Th-1 response. Patients 18 years of age or older who have had mild to moderately severe Crohn's disease for at least 4 months may be eligible for this study. Candidates will be screened with a medical history and possible review of medical records, physical examination, blood tests, electrocardiogram (EKG), urine and stool analyses and, for women, a pregnancy test. They will fill out a Crohn's Disease Activity Index questionnaire daily for 7 days and an Inflammatory Bowel Disease questionnaire. Participants will have G-CSF therapy. Before starting therapy, they will have a series of pre-treatment tests, including a colonoscopy and leukapheresis. Colonoscopy is an examination of the colon. For the procedure, patients are given a medication to lessen anxiety and any discomfort. An endoscope-a lighted flexible tube-is inserted into the rectum, allowing examination of the extent of inflammation. The endoscope can also be used to take pictures of the colon and extract tissue samples for testing (biopsy). Leukapheresis is a procedure for collecting quantities of white blood cells. Whole blood is collected through a needle placed in an arm vein and circulated through a machine that separates it into its components. The white cells are removed, and the rest of the blood is returned to the body, either through the same needle used to draw the blood or through another needle placed in the other arm. After the colonoscopy and leukapheresis, patients receive GCSF injections every day for 29 days. The patient or a caregiver, such as a family member, will be taught to give the injections. Blood samples will be collected on treatment days 4, 8, 11 and 15, and a physical examination and interview, blood tests

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and a stool exam will be done once a week. Patients will have a repeat colonoscopy and leukapheresis 24 hours after the last treatment dose (day 29). After the 29-day treatment, patients will be followed in the clinic as follows: - Week 4 after treatment - physical exam and interview, routine blood work and stool exam - Week 8 - interview and blood work - Week 16 - interview, blood work and stool exam - Week 24 - physical exam and interview, blood work, stool exam and colonoscopy Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025805 •

Immune Regulation in Ulcerative Colitis or Crohn's Disease Condition(s): Crohn's Disease; Inflammatory Bowel Disease; Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will investigate in patients with Crohn's disease and ulcerative colitis how the body's immune system controls inflammation in the gastrointestinal tract (stomach and intestines)-specifically, how lymphocytes (a type of white blood cell) function in inflammatory responses. This protocol does not involve any experimental treatments. Patients between the ages of 8 and 75 years of age with Crohn's disease or ulcerative colitis or symptoms of inflammatory bowel disease may be eligible for this study. Screening tests may include the following: medical history and physical examination, routine blood tests, examination of stool specimens, X-rays such as barium enema or upper GI series, proctosigmoidoscopy, colonoscopy, gastroduodenoscopy, and small bowel biopsy. Participants will receive medical treatment according to the best generally accepted measures for treating Crohn's disease or ulcerative colitis. This may include anti-inflammatory drugs, immunosuppressive drugs, and antibiotics to treat infections. A surgical consultation may be recommended for patients whose disease does not respond to medical treatment. If surgery to remove intestinal tissue is recommended, a qualified gastrointestinal surgeon will perform the procedure. In addition, participants may undergo the following procedures: - Blood drawing - No more than 450 milliliters (30 tablespoons, or 15 ounces) of blood will be taken from adults over a 6-week period. A maximum of 7 ml (1/2 tablespoon) of blood per kilogram (2.2. pounds) of body weight will be obtained from children within the same time period, with no more than 3 ml/kg taken at any one time. - Leukapheresis This procedure is done to collect large quantities of white blood cells. Whole blood is collected through a needle in an arm vein, similar to donating blood. The blood is circulated through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body, either through the same needle or through another needle in the other arm. - Intestinal biopsies - Intestinal tissue will be obtained during colonoscopy with intestinal biopsy in patients who require this procedure as part of their standard medical care. Patients are given a sedative to reduce anxiety, but are conscious during the procedure. A flexible tube is inserted into the rectum and large intestine, allowing the physician to see the intestinal mucosa. At various places, small pieces of tissue are plucked out. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001184

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Infliximab to Treat Children with Juvenile Rheumatoid Arthritis Condition(s): Juvenile Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will determine whether a stepwise increase of the drug infliximab (Remicade(r) (Registered Trademark)) controls juvenile rheumatoid arthritis more effectively than a fixed dose. It will look at the safety and effectiveness of increasing the dose to a maximum of 15mg/kg body weight per dose, examining the drug's effect on bone and cartilage, and whether it can improve abnormal growth, metabolism and hormones. Infliximab is approved for treating adults with rheumatoid arthritis and Crohn’s disease. Children between 4 and 17 years of age with active juvenile rheumatoid arthritis who do not respond adequately to standard therapy may be eligible for this study. Participants will receive nine infusions of infliximab during this 62-week study. The drug is given intravenously (IV, into a vein) over 2 hours. The first three infusions will be at a dose of 5 mg/kg of body weight. Children who improve on this regimen will receive another 6 infusions at the same dose. Children who do not significantly improve on 5 mg/kg at the end of 6 weeks (the third infusion) may continue with phase 2 of the study, in which they will be randomly assigned to receive either: 1) 6 additional doses of the drug at 5 mg/kg per dose, or 2) a gradually increased dose to a maximum of 15 mg/kg. In addition, all children will continue to take methotrexate at the same dose as when they entered the study. Participants will visit the NIH Clinical Center 12 times (about every 8 weeks) during the study for the following tests and procedures: - History and physical examination, including a complete joint exam - Puberty assessment - breast development in girls, testicle size in boys, and pubic hair - Height and weight measurements Children will have imaging studies (x-rays, MRI and Dexa scan) at the beginning and end of the study and will collect a 24-hour urine sample before each infliximab infusion. Patients may elect to have an endocrine evaluation. This involves Clinical Center hospitalizations for 1-1/2 days on visits 1, 4 and 12. Small amounts of blood will be drawn every 20 minutes (through an indwelling catheter to avoid multiple needle sticks) for 8 hours while the child sleeps. The blood will be examined for the normal rhythm of growth hormone and other substances in the body and how they are affected by arthritis. Participants will complete a questionnaire once a year for 2 years to provide information on their health status and any problems that might be related to the study drug. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029042

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ISIS 2302-CS22, A 6-Week, Active-Controlled Clinical Study to Evaluate the Effectiveness of Alicaforsen (ISIS 2302) in Patients with Mild to Moderate Active Ulcerative Colitis Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals

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Purpose - Excerpt: This is a multi-center trial to test the safety, efficacy and tolerability of alicaforsen (ISIS 2302), a new type of drug called an antisense drug, in patients with mild to moderate active Ulcerative Colitis (UC). Alicaforsen is designed to reduce the production of a specific protein, called ICAM-1, a substance that plays a significant role in the increase of inflammation and is likely to be involved in inflammatory bowel diseases such as ulcerative colitis. The ISIS 2302-CS22 study will examine the effects of one of two dosages of alicaforsen delivered by enema over a six-week period as compared to an active control, mesalamine enema (The probability of receiving the alicaforsen formulation is 2:1). The primary objective of this study is to evaluate the percentage reduction in DAI at Week 6. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063414 •

ISIS 2302-CS27, A 6-Week, Placebo-Controlled Clinical Study to Evaluate the Effectiveness of Alicaforsen (ISIS 2302) in Patients with Mild to Moderate Active Ulcerative Colitis. Condition(s): Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals Purpose - Excerpt: This is a multi-center trial in the US and Europe to test the safety, efficacy and tolerability of alicaforsen (ISIS 2302), a new type of drug called an antisense drug, in patients with mild to moderate active Ulcerative Colitis (UC). Alicaforsen is designed to reduce the production of a specific protein, called ICAM-1, a substance that plays a significant role in the increase of inflammation and is likely to be involved in inflammatory bowel diseases such as ulcerative colitis. The ISIS 2302-CS27 study will compare four dosing regimens and determine the minimum effective dose of alicaforsen enema in UC patients over six weeks as compared to a placebo enema. (The probability of receiving active formulation is 4:1). The primary objective of this study is to evaluate the percentage reduction in DAI at Week 6. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063830

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Quality of Life in Pediatric Inflammatory Bowel Disease Condition(s): Crohn's Disease; Ulcerative Colitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Measurement of the quality of life (QoL) of children and adolescents with inflammatory bowel diseases (IBD) has had little attention, despite the importance of understanding key factors affecting QoL, especially for measuring the effects of clinical trials to improve IBD outcomes. The main purpose of this pilot study is to examine the impact of clinical severity and treatment social factors on the quality of life

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(QoL) of a diverse population of children and adolescents with inflammatory bowel disease (IBD). Secondary purposes include determining the effects of sociodemographic factors on QoL and exploring the concordance of views of parents and children of QoL. The study aims are to 1) determine the associations of of clinical characteristics (condition type, activity/severity, and treatment) with specific components of general health-related quality of life and IBD-specific QoL; 2) describe the effects of sociodemographic characteristics (SES, age, and gender) on these measures; and 3) compare the views of different observers (parent and child with IBD) of the child's QoL. The study will apply both general and condition-specific QoL measures among a random sample of 250 children and adolescents with IBD, ages 5-18 years, in six clinical sites. We will obtain measures of QoL from both the child and a parent in each case. The study will obtain additional data regarding the subjects' clinical condition (condition type, severity/activity, treatment [including surgery], age of onset) and socioeconomic status (household structure and income). Main analyses will compare general and specific measures of QoL and examine the influence of clinical and sociodemographic variables on QoL, through multivariate regression techniques. We will also examine the differences in child and parent assessments of QoL. The information from this study will provide a stronger base for future studies of treatment and natural history of IBD. It will help to clarify the life domains that are affected by IBD and will inform interventions to improve QoL for children with IBD. Study Type: Observational Contact(s): James M Perrin, MD [email protected]; Aziz Chughtai, MPH Web Site: http://clinicaltrials.gov/ct/show/NCT00061737 •

Remission in Subjects with Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Abbott Laboratories Purpose - Excerpt: Purpose of the study is to test whether subjects who were previously in clinical remission in the M02-403 study can maintain their remission on adalimumab for a period of one year compared to placebo (an inactive substance). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055497

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Study of Immune Ablation With High-Dose Cyclophosphamide and Anti-Thymocyte Globulin Followed By Autologous Peripheral Blood Stem Cell Rescue in Patients With Severe Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Northwestern University Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of immune ablation with high-dose cyclophosphamide and anti-thymocyte globulin followed by autologous peripheral blood stem cell rescue in patients with severe Crohn's disease. II. Assess

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small intestinal absorption serially to determine if there is a relationship between small intestinal function and other clinical observations in patients treated with this regimen. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014703 •

Controlled Trial of 4-Aminosalicylic Acid in Patients with Small Bowel Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is no longer recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; University of Vermont Purpose - Excerpt: Objectives: I. Assess the efficacy and safety of 4-aminosalicylic acid in patients with active Crohn's disease of the small bowel. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004423

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Safety and Efficacy of Natalizumab in Combination with Remicade in the Treatment of Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is no longer recruiting patients. Sponsor(s): Elan Pharmaceuticals; Biogen Purpose - Excerpt: The purpose of this study is to determine the safety, tolerability, and efficacy of natalizumab in individuals diagnosed with active Crohn's Disease that are not in remission (CDAI greater than/equal to 150) and are currently taking Remicade. It is thought that natalizumab may stop the movement of certain cells, known as white blood cells, into bowel tissue. These cells are thought to cause damage in the bowel leading to the symptoms of Crohn's disease. Patients who complete this study may be eligible for long-term natalizumab therapy via extension protocol ELN100226-351. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055536

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Safety and Efficacy of Natalizumab in the Treatment of Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is no longer recruiting patients. Sponsor(s): Elan Pharmaceuticals; Biogen Purpose - Excerpt: The purpose of this study is to determine the safety and efficacy of natalizumab in individuals diagnosed with moderate to severely active Crohn's disease. It is thought that natalizumab may stop the movement of certain cells, known as white blood cells, into bowel tissue. These cells are thought to cause damage in the bowel leading to the symptoms of Crohn's disease.

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Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032786 •

Safety and Efficacy of Natalizumab in the Treatment of Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is no longer recruiting patients. Sponsor(s): Elan Pharmaceuticals; Biogen Purpose - Excerpt: The purpose of this study is to determine the safety and efficacy of natalizumab in individuals diagnosed with moderately to severely active Crohn's disease. It is thought that natalizumab may stop the movement of certain cells, known as white blood cells, into bowel tissue. These cells are thought to cause damage in the bowel leading to the symptoms of Crohn's disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032799

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Safety, Tolerability and Effectiveness of Natalizumab in Adolescents with Active Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is no longer recruiting patients. Sponsor(s): Elan Pharmaceuticals; Biogen Purpose - Excerpt: The purpose of this study is to determine the safety and tolerability of natalizumab in adolescents (ages 12-17) diagnosed with moderately to severely active Crohn's disease (CD). It is thought that natalizumab may stop the movement of certain cells, known as white blood cells, into bowel tissue. These cells are thought to cause damage in the bowel leading to the symptoms of Crohn's disease. Patients who complete this study may be eligible for long-term natalizumab therapy via extension protocol ELN100226-352. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055367

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Monoclonal Antibody Treatment of Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the safety and effectiveness of an experimental drug called J695 for treating patients with Crohn's disease-a long-term recurring inflammation of the small and large intestine. This disease is currently treated

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with steroids, sulfasalazine (Azulfidine), 5-ASA drugs (Pentasa, Asacol), immune suppressants, antibiotics, and an antibody against TNF-alpha. Despite the number and variety of available therapies for Crohn's disease, many patients do not respond adequately to treatment or they develop severe side effects from the medicines. Therefore, new treatments must be developed. J695 is an antibody that is identical to a human antibody but chemically changed so that it can attach to and eliminate an inflammatory chemical made by the body called interleukin-12 (IL-12). Animal studies have shown that eliminating IL-12 with an antibody can prevent inflammation in the gut and can also heal inflammation that has already developed. Patients 18 years of age and older who have had Crohn's disease for at least 4 months may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, chest X-ray, blood and urine tests, stool analysis and possibly a review of medical records. They will complete a Crohn's Disease Activity Index Questionnaire for 7 days. Participants will be randomly assigned to one of two treatment groups, as follows: Group 1 Patients in this group will receive an injection of either J695 or placebo (a solution that does not contain any active medicine) under the skin on day 1 of the study, on day 29, and then weekly for a total of seven injections. After the last injection, patients will be followed for an additional 18 weeks. They will be monitored periodically throughout the study with physical examinations, disease activity index scores, and blood and urine tests. Group 2 Patients in group 2 will receive an injection of J695 or placebo on day 1 of the study and then weekly for a total of six injections. They will be followed for an additional 18 weeks. Patients will be monitored as described above for group 1. Participants may be asked to undergo additional tests as part of a sub-study in this protocol. These include colonoscopies to examine changes in inflammation in the gut and blood tests to analyze changes in the cells and body chemicals that affect the inflammation. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007163 •

Multicenter Trial For Patients With Acute Crohn's Disease Condition(s): Crohn's Disease Study Status: This study is not yet open for patient recruitment. Sponsor(s): IVAX Research Purpose - Excerpt: The study is to see if etiprednol dicloacetate is safe and effective for the treatment of acute Crohn's disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035503

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Phase III Randomized Study of Anti-Tumor Necrosis Factor Chimeric Monoclonal Antibody (cA2) for Patients with Enterocutaneous Fistulae as a Complication of Crohn's Disease Condition(s): Crohn's Disease

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Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development; Centocor Purpose - Excerpt: Objectives: I. Evaluate the efficacy of chimeric monoclonal antibody (cA2) compared with placebo in closure of enterocutaneous fistulae in patients with Crohn's disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004941

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 “Crohn’s disease” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 6. PATENTS ON CROHN’S DISEASE 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 “Crohn’s disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Crohn’s disease, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Crohn’s Disease By performing a patent search focusing on Crohn’s disease, 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. The following is an 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on Crohn’s disease: •

Amide therapeutics and methods for treating inflammatory bowel disease Inventor(s): Greenwood Van-Meerveld; Beverly (Oklahoma City, OK), Irwin; Ian (Palo Alto, CA), Garland; William A. (Los Gatos, CA), Flitter; William D. (Mountain View, CA) Assignee(s): Centaur Pharmaceuticals, Inc. (Sunnyvale, CA) Patent Number: 6,486,349 Date filed: November 17, 2000 Abstract: Disclosed are methods for treating or preventing inflammatory bowel disease (IBD) using amide and related compounds. Pharmaceutical compositions containing amide compounds which are useful for the treatment or prophylaxis of IBD are also disclosed. Excerpt(s): This invention relates to the treatment of inflammatory bowel disease (IBD). More specifically, this invention is directed to methods for treating or preventing IBD using amide compounds. This invention is also directed to pharmaceutical compositions containing amide compounds which are useful for the treatment or prophylaxis of IBD.... The term inflammatory bowel disease ("IBD") describes a group of chronic inflammatory disorders of unknown causes involving the gastrointestinal tract ("GI tract"). The prevalence of IBD in the US is estimated to be about 200 per 100,000 population or approximately 500,000 people. Patients with IBD can be divided into two major groups, those with ulcerative colitis ("UC") and those with Crohn's disease ("CD").... In patients with UC, there is an inflammatory reaction primarily involving the colonic mucosa. The inflammation is typically uniform and continuous with no intervening areas of normal mucosa. Surface mucosal cells as well as crypt epithelium and submucosa are involved in an inflammatory reaction with neutrophil infiltration. Ultimately, this situation typically progresses to epithelial damage with loss of epithelial cells resulting in multiple ulcerations, fibrosis, dysplasia and longitudinal retraction of the colon. Web site: http://www.delphion.com/details?pn=US06486349__

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Aryl nitrone therapeutics and methods for treating inflammatory bowel disease Inventor(s): Van-Meerveld; Beverly Greenwood (Oklahoma City, OK), Garland; William A. (Los Gatos, CA), Flitter; William D. (Mountain View, CA), Irwin; Ian (Palo Alto, CA) Assignee(s): Centaur Pharmaceuticals, Inc. (Sunnyvale, CA) Patent Number: 6,545,056 Date filed: November 17, 2000 Abstract: Disclosed are methods for treating or preventing inflammatory bowel disease (IBD) using aryl nitrone compounds. Pharmaceutical compositions containing aryl nitrone compounds which are useful for the treatment or prophylaxis of IBD are also disclosed. Excerpt(s): This invention relates to the treatment of inflammatory bowel disease (IBD). More specifically, this invention is directed to methods for treating or preventing IBD

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using aryl nitrone compounds. This invention is also directed to pharmaceutical compositions containing aryl nitrone compounds which are useful for the treatment or prophylaxis of IBD.... The term inflammatory bowel disease ("IBD") describes a group of chronic inflammatory disorders of unknown causes involving the gastrointestinal tract ("GI tract"). The prevalence of IBD in the US is estimated to be about 200 per 100,000 population or approximately 500,000 people. Patients with IBD can be divided into two major groups, those with ulcerative colitis ("UC") and those with Crohn's disease ("CD").... In patients with UC, there is an inflammatory reaction primarily involving the colonic mucosa. The inflammation is typically uniform and continuous with no intervening areas of normal mucosa. Surface mucosal cells as well as crypt epithelium and submucosa are involved in an inflammatory reaction with neutrophil infiltration. Ultimately, this situation typically progresses to epithelial damage with loss of epithelial cells resulting in multiple ulcerations, fibrosis, dysplasia and longitudinal retraction of the colon. Web site: http://www.delphion.com/details?pn=US06545056__ •

Benzamide therapeutics for the treatment of inflammatory bowel disease Inventor(s): Irwin; Ian (Palo Alto, CA), Garland; William A. (Los Gatos, CA), Flitter; William D. (Mountain View, CA) Assignee(s): Centaur Pharmaceuticals, Inc. (Sunnyvale, CA) Patent Number: 6,194,465 Date filed: May 18, 1999 Abstract: Benzamides are disclosed to be useful for treating and preventing inflammatory bowel disease. Excerpt(s): This invention relates to the treatment of inflammatory bowel disease. More specifically, it relates to methods and pharmaceutical compositions for the treatment and prophylaxis of IBD.... The term inflammatory bowel disease ("IBD") describes a group of chronic inflammatory disorders of unknown causes involving the gastrointestinal tract ("GI tract"). The prevalence of IBD in the US is estimated to be 200 per 100,000 population (approximately 500,000 people). Patients with IBD can be divided into two major groups, those with ulcerative colitis ("UC") and those with Crohn's disease ("CD").... In patients with UC, there is an inflammatory reaction primarily involving the colonic mucosa. The inflammation is typically uniform and continuous with no intervening areas of normal mucosa. Surface mucosal cells as well as crypt epithelium and submucosa are involved in an inflammatory reaction with neutrophil infiltration. Ultimately this situation typically progresses to epithelial damage with loss of epithelial cells resulting in multiple ulcerations, fibrosis, dysplasia and longitudinal retraction of the colon. Web site: http://www.delphion.com/details?pn=US06194465__

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Colonic delivery of nicotine to treat inflammatory bowel disease Inventor(s): Rhodes; John (Cardiff, GB), Sandborn; William (Rochester, MN) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 6,166,044 Date filed: March 23, 1999 Abstract: A method is provided to treat inflammatory bowel disease by locally administering to the colon an effective amount of nicotine or a pharmaceutically acceptable salt thereof, preferably via formulations adapted for delayed oral release or rectal administration. Further provided is a novel formulation for the oral administration of nicotine comprising a polyacrylic polymer complexed with nicotine. Excerpt(s): Inflammatory bowel disorders or diseases (IBD) encompass a spectrum of overlapping clinical diseases that appear to lack a common etiology. IBD, however, are characterized by chronic inflammation at various sites in the gastrointestinal (GI) tract. Illustrative IBD are regional enteritis (or Crohn's disease), idiopathic ulcerative colitis, idiopathic proctocolitis, pouchitis and infectious colitis. Symptoms of IBD may include persistent diarrhea, abdominal pain, fever, weight loss, joint pain, skin lesions and general fatigue. The inflammatory conditions of ulcerative colitis are confined to the colon, unlike Crohn's disease which can involve any portion of the intestinal tract.... Current treatment for IBD includes oral, IV and colonically administered corticosteroids and oral and colonically administered 5-aminosalicylic acid (Edsbacker et al., Gastroenterology 104:A695 (1993); Greenberg et al., NEJM 317:1625-29 (1987). cyclosporin is another treatment for IBD, but this is limited to oral administration since colonic administration was not efficacious; (Gastroenterology 1994, 108:1429-1435).... Several types of colonic drug delivery systems are currently available, including enemas (Sutherland et al., Med. Clin. North Amer., 74:119 (1990)); rectal foams (Drug Ther. Bull., 29:66 (1991)); and delayed oral release formulations in the form of enteric-coated capsules which disintegrate at pH7 in the terminal ileum (Schroeder et al., NEJM, 317:1625 (1987)). Web site: http://www.delphion.com/details?pn=US06166044__

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Composition for and treatment of inflammatory bowel disease by colon administration of N-acetylglucosamine Inventor(s): Murch; Simon (c/o University Department of Paediatric Gastroenterology Royal Free Hospita, London NW3 2QG, GB), French; Ian W. (6905 Highway 9 R.R. 1, Caledon East, Ontario, CA) Assignee(s): none reported Patent Number: 6,046,179 Date filed: March 3, 1999 Abstract: This invention relates to a novel composition and a novel method of treating inflammatory bowel disease (IBD). More particularly, this invention pertains to a novel composition containing N-acetyl-glucosamine (NAG) as an active IBD treating agent and a pharmacologically suitable carrier, and a method of administering the composition to the colon to treat IBD in a person afflicted with IBD. A composition for treating inflammatory bowel disease in a patient suffering from inflammatory bowel disease comprising: (a) a therapeutic amount of N-acetyl-glucosamine; and (b) a

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pharmacologically acceptable carrier, adapted to be administered colonically to said patient. Excerpt(s): This invention relates to novel compositions and novel methods of treating inflammatory bowel disease (IBD). More particularly, this invention pertains to novel compositions containing N-acetyl-glucosamine (NAG) as an active IBD treating agent and a pharmacologically and colonically suitable carriers for the NAG, and a method of administering the compositions to the colon to treat IBD in a person afflicted with IBD.... In general terms the "bowel" extends from the stomach to the anus and comprises the small intestine and the large intestine. The small intestine comprises three main sections, the duodenum (which is adjacent to the stomach), the jejunum (which is intermediate) and the ileum (which is distant to the stomach). The large intestine (which is termed the colon) is joined to the remote end of the ileum of the small intestine by the ileocecal valve. The large intestine (colon) comprises two main sections, the caecum (which is connected to the ileum of the small intestine), and the rectum, which is the remote part of the large intestine (colon). The remote end of the rectum is connected to the anus.... The term "inflammatory bowel disease" (IBD) is a generic expression which encompasses a number of specific bowel diseases including ulcerative colitis, chronic proctitis and Crohn's disease. These diseases may or may not overlap with one another to a certain extent. When they do, they blur the boundaries between the various types of IBD afflictions. Ulcerative colitis is a chronic, non-specific inflammatory bowel disease which involves ulcerative lesions of the colon. Chronic proctitis comprises inflammation of the colon and often the rectum. Crohn's disease appears as several types of intestinal inflammation but most often the term refers to inflammation of the terminal portion of the ileum. Synonyms of Crohn's disease are regional enteritis (the intestine) or regional iletis, although the latter is not always apt since Crohn's disease is not limited to the ileum. Crohn's disease often involves diseases, fistulas (deep sinnous passages or tracts in the colon), perianal ulcerations and narrowing of the intestinal lumen (strictures). Surgical removal of the diseased portion of the intestine (termed a colectomy, or ileectomy) is reserved for those cases which are most resistant to treatment, since about half of those treated by surgery experience a recurrence of the disease in another segment of the intestine. The most common clinical symptoms of Crohn's disease include abdominal pain, fever, anorexia, weight loss and a right lower quadrant "fullness". Web site: http://www.delphion.com/details?pn=US06046179__ •

Controlled release polypeptide compositions and methods of treating inflammatory bowel disease Inventor(s): Gombotz; Wayne R. (Kirkland, WA), Wee; SiowFong (Edmonds, WA) Assignee(s): Immunex Corporation (Seattle, WA) Patent Number: 6,036,978 Date filed: April 23, 1996 Abstract: The invention pertains to a controlled release pharmaceutical formulation that has an effective amount of a polypeptide selected from the group consisting of: (a) TNFR, (b) IL-1R, (c) IL-1ra, (d) IL-6R and (e) a monoclonal antibody that is immunoreactive against TNF, IL-6 or IL-1; wherein the polypeptide is encapsulated in alginate. The invention also pertains to methods of treating inflammatory bowel disease by administering the above composition to a patient in need thereof.

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Excerpt(s): This invention pertains to controlled release pharmaceutical compositions containing a polypeptide and a salt of an alginic acid. This invention also is directed to methods of treating inflammatory bowel diseases that are mediated by tumor necrosis factor, interleukin-6 or interleukin-1 by administering such controlled enteric release formulations to a patient.... Inflammatory bowel disease (IBD) is marked by the presence of chronic inflammation of the gastrointestinal tract. One form of the disease is ulcerative colitis, a disease that affects the large bowel exclusively and which is characterized by mucosal ulceration, superficial inflammatory-cell infiltration of the bowel wall, and in extensive long-standing cases, neoplastic transformation. Another form of the disease is termed Crohn's disease (regional enteritis or regional ileitis). Crohir's disease can affect any part of the alimentary canal, from the mouth to the rectum, although it is commonly involved in the terminal ileum and the ascending colon. It has been recently reported that long-standing ulcerative colitis in patients is correlated to an increased incidence of colorectal cancer. See, for example, LennardJones, et al., Gut, 31:800-806 (1986); and Ekbom et al., N Engl. J. Med., 323:1228-1233 (1988). Furthermore, Crohn's disease has been firmly associated with an increased risk of colorectal cancer, Ekbom et al., Lancet, 336:357-359 (1990).... Approximately 10 percent of the cases involving either Crohn's disease or ulcerative colitis involve the same anatomic location, i.e., the large bowel. These two forms of inflammation are partly and possibly wholly distinct in their pathogenic events, however it also is likely that they share important common pathophysiologic processes. It was reported by odolsky, N. Engl. J. Med., 325 (13): 928-937 (1991), that certain cytokines are mediators of the inflammation, namely, interlieukin-1 (IL- 1) and interleukin-6 (IL-6). Along with IL-1 and IL-6, Stevens, et al., Dig. Dis. and Sciences, 37 (6):818-826 (1992), recently reported that the pro inflammatory cytokine tumor necrosis factor-alpha (TNF-(.alpha.) was expressed in the intestine of patients with IBD. Web site: http://www.delphion.com/details?pn=US06036978__ •

Diagnostic assay for latent matrix metallo-proteinase No. 9 and use thereof in the diagnosis of rheumatoid and inflammatory arthritis and inflammatory bowel disease Inventor(s): Ahrens; Diane (Beacon Falls, CT), Niedbala; Michael J. (Oxford, CT) Assignee(s): Bayer Corporation (Tarrytown, NY) Patent Number: 5,674,754 Date filed: April 27, 1995 Abstract: Elevated plasma levels of proMMP-9 and proMMP-9/TIMP-1 complex have been shown to correlate with and are useful in aiding the diagnosis of rheumatoid arthritis and inflammatory bowel disease; a hybridoma which produces a monoclonal antibody which specifically binds to and recognizes proMMP-9 and proMMP-9/TIMP-1 complex is disclosed and is designated mAb 277.13. Excerpt(s): The present invention relates to assay methods for detecting levels of specific enzymes in biological samples. More particularly, the present invention relates to methods for the detection of Matrix Metallo-Proteinase No. 9 (hereinafter "MMP" when referring to the class of matrix metallo-proteinases and "MMP-9" when referring to matrix metallo-proteinase No. 9 in particular). The inventive assay method is useful to diagnose rheumatoid arthritis, inflammatory arthritis (including psoriatic, gout, systemic lupus erythematous, and spondyl arthritis) and inflammatory bowel disease (hereinafter "IBD").... Physiological variances in MMP levels are known. For instance, significant increases in plasma 72 kDa gelatinase (MMP-2 levels have been observed in

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women during the second half of pregnancy as compared to early pregnancy and nonpregnant women (Zucker et al., 1992, J. Immunol. Methods, 148: 189).... Pathologically, MMPs have been identified as associated with several disease states. For example, anomalous MMP-2 levels have been detected in lung cancer patients, where it was observed that serum MMP-2 levels were significantly elevated in stage IV disease and in those patients with distant metastases as compared to normal sera values (Garbisa et al., 1992, Cancer Res., 53: 4548). Also, using an ELISA methodology, it was observed that plasma levels of MMP-9 were elevated in patients with colon and breast cancer (Zucker et al., 1993, Cancer Res. 53: 140). However, these researchers did not investigate potential relationships among MMP-9 plasma levels in arthritis and IBD. Web site: http://www.delphion.com/details?pn=US05674754__ •

Gastroprotective flavone/flavanone inflammatory bowel disease

compounds

with

therapeutic

effect

on

Inventor(s): Yoo; Moohi (Seoul, KR), Baik; Nam Gi (Kyoungki-do, KR), Ahn; Byoung Ok (Kyunggi-do, KR), Lim; Joong In (Seoul, KR), Lim; Geun Jho (Seoul, KR), Lee; Sang Deuk (Seoul, KR), Kim; Soon Hoe (Kyoungki-do, KR), Kim; Won Bae (Seoul, KR), Son; Mi Won (Kyoungki-do, KR), Ryu; Byung Kwon (Seoul, KR), Kim; Ik Yon (Kyoungki-do, KR), Oh; Tae Young (Kyunggi-do, KR), Shin; Hee Chan (Seoul, KR), Yang; Jae Sung (Seoul, KR), Kim; Dong Sung (Kyoungki-do, KR) Assignee(s): Dong a Pharmaceutical Co., Ltd. (KR) Patent Number: 6,025,387 Date filed: January 14, 1999 Abstract: The present invention relates to novel flavone/flavanone compounds or their pharmaceutically acceptable salts and process for preparation thereof for protecting gastrointestinal tracts against gastritis, ulcers and inflammatory bowel disease. Excerpt(s): The present invention relates to novel flavone/flavanone compounds or their pharmaceutically acceptable salts, and process for preparation thereof for protecting gastrointestinal tracts against gastritis, ulcers and inflammatory bowel disease.... Although the incidence of gastric ulceration, duodenal ulceration or gastritis has been declining over the last decade, about 10% of the population will develop this condition at some time during their lives. The precise cause of these diseases remains uncertain despite of intensive clinical and laboratory research, but it is explained that they are induced from imbalance in equlibrium between potentially damaging factor present in the lumen of the stomach or duodenum and the process which enable these tissues to resist autodigestion.... The first line therapy for gastritis and gastric ulcer is to promote the effects of treatments by attenuating the attacking factors by administering antisecretory agents such as antacid, H2 antagonists and proton pump inhibitors. However, it has been reported that in the cases of omeprazole or long acting H2 antagonists, the duration of action was so long more than 24 hours that their long-term administration to rats caused dysplasia in epidermal cells of mucous membrane in gastrointestinal tracts (Ekman, L. et al., Scand. J. Gastroentrol.1985, 20 suppl.108: 53). And long-term administration of antisecretory agents is frequently associated with formation of gastric tumors in animals (Garner, A., Advances in Drug Therapy of Gastrointestinal Ulceration; Garner, A. and Whittle, B. J. R.(Eds.), Wiley & Sons, 1989, 275-88). Furthermore, a majority of patients with peptic ulcer disease have acid outputs within the normal range (Baron, J. H., Clinical Tests of Gastric Secretion. Macmillan, London, 1978, 86-119), so the treatments with antisecretory agents are not fundamental

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therapy and have a little effect on the prevention of recurrence, though they enhance acute healing of ulcer. Web site: http://www.delphion.com/details?pn=US06025387__ •

Inflammatory bowel disease first step assay system Inventor(s): Rose; Steven L. (Escondido, CA), Walsh; Michael J. (San Diego, CA) Assignee(s): Prometheus Laboratories, Inc. (San Diego, CA) Patent Number: 6,218,129 Date filed: May 15, 1998 Abstract: The present invention provides a highly sensitive method of diagnosing inflammatory bowel disease (IBD) in an individual. The method includes the steps of isolating a sample from the individual; determining by non-histological means whether the sample is positive for anti-neutrophil cytoplasmic antibodies (ANCA); determining whether the sample is positive for anti-Saccharomyces cerevisiae immunoglobulin A (ASCA-IgA); determining whether the sample is positive for anti-Saccharomyces cerevisiae immunoglobulin G (ASCA-IgG); and diagnosing the individual as having IBD when the sample is positive for ANCA, ASCA-IgA or ASCA-IgG, and diagnosing the individual as not having IBD when the sample is negative for ANCA, ASCA-IgA and ASCA-IgG, provided that the method does not include histological analysis of neutrophils. Excerpt(s): The invention relates generally to the fields of inflammatory bowel disease and immunology and more specifically to serological methods for distinguishing inflammatory bowel disease from other disorders.... Inflammatory bowel disease (IBD), which occurs world-wide and afflicts millions of people, is the collective term used to describe two gastrointestinal disorders of unknown etiology: Crohn's disease (CD) and ulcerative colitis (UC). IBD together with irritable bowel syndrome (IBS) will affect onehalf of all Americans during their lifetime, at a cost of greater than $2.6 billion dollars for IBD and greater than $8 billion dollars for IBS. A primary determinant of these high medical costs is the difficulty of diagnosing digestive diseases. The cost of IBD and IBS is compounded by lost productivity, with persons suffering from these disorders missing at least 8 more days of work annually than the national average.... Inflammatory bowel disease has many symptoms in common with irritable bowel syndrome, including abdominal pain, chronic diarrhea, weight loss and cramping, making definitive diagnosis extremely difficult. Of the 5 million people suspected of suffering from IBD in the U.S., only 1 million are diagnosed as such. The difficulty in differentially diagnosing IBD and IBS hampers early and effective treatment of these diseases. Thus, there is a need for rapid and sensitive testing methods for definitively distinguishing IBD from IBS. Web site: http://www.delphion.com/details?pn=US06218129__

Patents 263

•

Inflammatory bowel disease preventive and curative agent containing zinc Lcarnosine salt as active ingredient Inventor(s): Nishimura; Yasuhiro (Fujiidera, JP), Yoneda; Tomoyuki (Kumagaya, JP), Yoshikawa; Toshikazu (Uji, JP) Assignee(s): Zeria Pharmaceutical Co., Ltd. (Tokyo, JP), Hamari Chemicals, Ltd. (Osaka, JP) Patent Number: 5,238,931 Date filed: July 5, 1991 Abstract: An agent for the prevention and treatment of inflammatory bowel disease (IBD) containing at least one of zinc L-carnosine salts and complexes as an active ingredient. A use of the zinc L-carnosine salts or complexes and a therapeutic method of IBD by using the same are also disclosed. Excerpt(s): The present invention relates to inflammatory bowel disease (hereinafter referred to as IBD) preventive and curative agents containing a zinc L-carnosine salt or complex as an active ingredient, and a therapeutic method using the same.... As a cause of this disease, various theories such as infection theory, allergy theory, enzyme theory and the like have been presented. However, there is not established theory so far, and the cause is still unknown. In the meantime, autoimmunity theory is paid attention to since Broberger et al. reported that anticoli antibody was found from a patient's blood serum of this disease (see J. Exp. Med., Volume 115: pp. 13-26, 1962).... For the treatment of this disease, there has been employed two types of basic drugs which are salazosulfapyridine and adrenocortical steroid drugs. Further, an immunosuppressant such as azathioprine, metronidazole, antibiotics for preventing secondary infection are used, too. The salazosulfapyridine, a common preparation for the treatment of this disease is mostly decomposed into two metabolites of sulfapyridine and 5aminosalicyclic acid by an action of enteric bacteria after oral dosage. It is considered that the salazosulfapyridine owes its effects to the 5-aminosalicyclic acid, and it seems that side-effects frequently observed are caused by the sulfapyridine of metabolite (see Khan et al., Lancet, p. 2892, 1977). Also, since the 5-aminosalicylic acid is unstable, and in effect, little amount of this substance reaches a colon when orally dosed, therapeutic effect is weak. As the side-effects of the salazosulfapyridine, nausea, vomiting, anorexia, exanthema, headache, hepatopathy, leukopenia, abnormal erythrocyte, proteinuria, diarrhea and the like are reported. Further, as the adrenocortical steroid drug, prednisolone is usually used in oral dosage, clysma, suppository, vein injection or the like with a strong side-effects such as gastric ulcer and caput femoris necrosis due to a long period of use. Web site: http://www.delphion.com/details?pn=US05238931__

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Inhibition of nitric oxide formation in inflammatory bowel disease Inventor(s): Tilton; Ronald G. (Sugarland, TX), McDaniel; Michael L. (Glendale, MO), Corbett; John A. (St. Louis, MO), Williamson; Joseph R. (St. Louis, MO) Assignee(s): Washington University (St. Louis, MO) Patent Number: 5,710,181 Date filed: March 25, 1996

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Abstract: A method is disclosed for inhibiting nitric oxide formation in a warm blooded mammal afflicted with inflammatory bowel disease which comprises administering to said mammal an effective nitric oxide inhibitory amount of aminoguanidine. Excerpt(s): This invention relates to a method of inhibiting nitric oxide formation in warm blooded mammals and, more particularly, to the administration of a nitric oxide synthase inhibitor for the treatment of a pathophysiologlcal condition manifested by acute and chronic inflammation.... Nitric oxide synthase (NOS) catalyzes the mixed functional oxidation of L-arginine to L-citrulline and nitric oxide (NO.cndot.) (Stuehr et al., Proc Natl Acad Sci USA 88: 7773, 1991). NO.cndot. appears to function as either a signaling or an effector molecule depending on the mount produced and on the isoform of the enzyme. The constitutive isoform of nitric oxide synthase produces small mounts of NO.cndot. which activate guanylate cyclase resulting in the formation of cGMP which mediates endothelium--dependent relaxation (Moncada et al., Pharmacol Rev 43: 109, 1991) and neural transmission (Garthwaite, Trends Neurol Sci 14: 60, 1991). NO.cndot. is produced in much larger mounts by the cytokine and endotoxin inducible nitric oxide synthase (iNOS) isoform, and in macrophages functions as an effector molecule which appears to mediate the cytotoxic actions of macrophages on target cells (Hibbs et al., Nitric Oxide from L-Arginine: A Bioregulatory System, S. Moncada and E. Higgs, Eds. Elsevier, N.Y., pp. 189-223, 1990). Since NO.cndot. is a potent vasodilator and increases blood flow, and since vasoactive agents (such as histamine and bradykinin), which stimulate NO.cndot. production increase both blood flow and vascular permeability, NO.cndot. may be a candidate for mediating increases in blood flow and vascular permeability induced by diabetes and elevated glucose (Pugliese et al., Diabetes/Metabolism Reviews 7: 35, 1991).... Recently, Interleukin-1 (IL-1) has been shown to induce the expression of the cytokine inducible isoform of nitric oxide synthase in pancreatic islets. The production of NO.cndot. has been proposed to be the effector molecule which mediates IL-1's inhibitory effects on islet function (Southern et al., FEBS Lett 276: 42, 1990 and Corbett et al., Biochemical J 287: 229, 1992). Generation of an IL-1-induced EPR detectable iron-nitrosyl complex, which is prevented by N.sup.G monomethyl-L-arginine (NMMA), has been used to confirm the formation of nitric oxide by islets (Corbett et al., J Biol Chem 266: 21351-21354, 1991). Also, the protein synthesis inhibitor, cycloheximide has been shown to block IL-1-induced nitrite formation, cGMP accumulation, and EPR detectable iron-nitrosyl complex formation by islets, thus establishing that IL-1 induces the cytokine inducible isoform of nitric oxide synthase in pancreatic islets (Corbett et al., Biochem J 287: 229, 1992). Web site: http://www.delphion.com/details?pn=US05710181__ •

Method and composition for the treatment of inflammatory bowel disease Inventor(s): Schwartz; Marshall Z. (Bryn Mawr, PA) Assignee(s): The Nemours Foundation (Jacksonville, FL) Patent Number: 6,319,899 Date filed: September 14, 1999 Abstract: The present invention relates to a method and composition for treating a patient having a condition characterized as inflammatory bowel disease with an effective dose of HGF. Mucosal damage and histologic lesions are reduced by administering HGF to patients suffering from the same. HGF may be administered to the patient lumenally or systemically.

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Excerpt(s): The present invention relates broadly to the treatment of inflammatory bowel diseases in a patient. More particularly, the invention relates to treating a patient having an inflammatory bowel disease condition with Hepatocyte Growth Factor ("HGF").... Chronic Ulcerative Colitis ("CUC") and Crohn's Disease ("CD"), generally referred to as Inflammatory Bowel Disease ("IBD"), are devastating disorders with an unknown etiology. Current medical therapy can control symptomatic exacerbations of IBD, but does not provide a cure. Progress in understanding the pathogenesis of IBD has been slowed by the lack of availability of animal models that exhibit the chronic, spontaneous, relapsing gastrointestinal ("GI") inflammation that is symptomatic of human IBD. Numerous murine and rat experimental models exist that possess some but not all of the features of human IBD.... A study has shown that the introduction of HLAB27 and human.beta..sub.2 -microglobulin genes into Fisher (F344) rats induces spontaneous chronic GI inflammation. Hammer et al., Cell 63: 1099-1112 (1990). In this model, rats spontaneously develop a chronic inflammatory disease that includes most of the clinical and pathologic features of the B27-associated disorders in humans. The most prevalent site of inflammation in these transgenic rats appears to be localized to the gastro-intestinal tract, and the most persistent finding is diarrhea developing in 100% of the animals at 20 weeks of age. Hammer et al., Cell 63: 1099-1112 (1990); Elson et al., Gastroenterology 109: 1344-1367 (1995). Because it closely approximates the human disease, as will be described in detail below, this transgenic rat model was used to study the therapeutic benefit of HGF as a treatment for IBD. Web site: http://www.delphion.com/details?pn=US06319899__ •

Method and compounds for treating inflammatory bowel disease Inventor(s): Pitzele; Barnett S. (Skokie, IL), Lambert; Howard J. (Deerfield, IL) Assignee(s): G. D. Searle & Co. (Skokie, IL) Patent Number: 4,312,806 Date filed: March 2, 1981 Abstract: The present invention relates to novel compounds and a method for the prophylaxis and treatment of Inflammatory Bowel Disease (IBD) via the administration of an effective amount in a suitable pharmaceutical dosage form of an azobenzene compound of formula I or a pharmacologically acceptable salt, which is reductively cleaved to 5-aminosalicylic acid (5-ASA) by bacteria in the large intestine. Excerpt(s): The present invention provides novel compounds and a novel method for the treatment of Inflammatory Bowel Disease (IBD) with certain azobenzene compounds. In particular it provides 5,5'-azobis-salicylic acid, a compound of formula I of Chart A, and its pharmacologically acceptable salts, which are reductively cleaved to 5-amino salicylic acid by the action of bacteria in the large intestine, and a method of treating or preventing IBD using said compounds.... In addition, it provides novel compounds of formula V of Chart A, the divalent alkali earth metal salts of 5,5'-azobissalicylic acid. In addition, it further provides the novel trivalent aluminum salt of 5,5'azobis-salicylic acid, formula VI of Chart A.... Treatment of IBD has been accomplished by several pharmacological routes. Notably, adrenocorticosteroids, belladonna alkaloids, belladonna derivatives, bismuth subcarbonate, kaolin and sulfasalzine are in current use. The adrenocorticosteroids may mask symptoms of intestine perforation and peritonitis and are generally only used for short term therapy, (Goodman & Gilman 4th Ed. pg. 1634 (1970)) and Major complications may occur despite corticosteroid therapy. The belladonna alkaloids and derivatives are largely considered ineffective in IBD.

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(Goodman & Gilman 4th Ed. pg. 544 (1970). Bismuth subcarbonate is a mechanical protectant and merely prevents further irritation of the condition without any direct effect on the condition. Kaolin is an absorbent which absorbs bacteria and toxins in the colon, but it is doubtful that appreciable activity is retained by the time it reaches the lower bowel. (Goodman and Gilman 4th ed. pg. 990 (1970). Sulfasalazine (SS) is the drug of choice currently for IBD. Its structure is shown in formula II of Chart A. SS is a prodrug, that is, upon administration, biological processes act upon SS to produce the drug which has the desired biological activity. Upon oral administration, about one-third of a given dose of SS is absorbed from the small intestine. The remaining two-thirds are split by azo-reductase from bacterial flora into sulphapyridine (SP), formula III of Chart A, and 5-aminosalicylic acid (5-ASA) formula IV of Chart A. (Physican's Desk Reference 31st ed. pg. 1250 (1977) See also Klotz, New Eng J. of Med 303, 1499 (1980). It has been determined that the activity of SS comes from the 5-ASA produced. SS is effective as a pro-drug because its relative insolubility prevents its complete absorption in the small intestine thus allowing delivery of SS to the site of administration, i.e., the large intestine. Given separately, both SP and 5-ASA are almost completely absorbed from the small intestine. While effective, SS has several severe side effects including blood dyscrasias and hypersensitivety reactions. This toxicity of SS is due almost entirely to the SP produced. Web site: http://www.delphion.com/details?pn=US04312806__ •

Method for producing an animal model for inflammatory bowel disease including ulcerative colitis Inventor(s): Szabo; Sandor (Brookline, MA) Assignee(s): Brigham and Women's Hospital (Boston, MA) Patent Number: 5,214,066 Date filed: April 18, 1990 Abstract: A new animal model for Inflammatory Bowel Disease, including idiopathic ulcerative colitis and Chron's disease, as well as methods for problems such as an animal, is provided. Chronic ulcerative condition is induced by topical administration of a sulfhydryl blocker, such as N-ethylmaleimide or iodoacetamide, to the colon. The new animal model is useful for studying the pathogenesis of chronic ulcerative disease, and prevention and treatment thereof, and for evaluating drugs suspected of being useful in the treatment of same. Excerpt(s): This invention relates to an animal model useful for studying the early development and treatment of Inflammatory Bowel Disease, including ulcerative colitis and Crohn's disease, in mammals, particularly humans.... Ulcerative colitis (UC) and Crohn's disease, the two major forms of idiopathic Inflammatory Bowel Disease (IBD) in humans, are widespread and poorly understood disorders (Kirsner, J. B., et al., eds., Inflammatory Bowel Disease: 3rd ed., Lea and Febiger, Philadelphia (1988); Goldner, F. H., et al., Idiopathic Inflammatory Bowel Disease, in Stein, J. H., ed., Internal Medicine, Little Brown & Co., Boston, pp. 369-380 (1990); Cello, J. P., et al.. Ulcerative Colitis, in Sleisenger, M. H., et al.. eds., Gastrointestinal Disease: Pathophysiology Diagnosis Management, W. B. Saunders Co., Philadelphia, p. 1435 (1989)). The separation of these idiopathic diseases of unknown etiology from other forms of colitis and ileitis caused by infectious agents, drugs, or the solitary rectal ulcer syndrome and collagenous colitis is not always respected in the literature (Riddell, R. H., ed., Pathology of Drug-induced and Toxic Diseases, Churchill Livingstone, New York (1982)). The diagnosis of IBD of

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known and unknown etiology is often not only difficult but almost impossible, e.g., during serious local complications such as hemorrhage, toxic dilation, perforation, inflammatory polyps and strictures (Riddell, R. H., ed., Pathology of Drug-induced and Toxic Diseases, Churchill Livingstone, New York (1982)).... The pathology of ulcerative colitis usually refers to a more superficial mucosal disease in contrast to Crohn's disease with its deep, often transmucosal involvement and fissures (Riddell, R. H., ed., Pathology of Drug-induced and Toxic Diseases, Churchill Livingstone, New York (1982); Morrison, B. C., et al.. eds., Gastrointestinal Pathology, 2d ed., London (1979); Fenoglio-Preiser, C. M., et al., eds., Gastrointestinal Pathology: An Atlas and Text, Raven Press, New York (1989); Goldman, H., et al., Hum. Pathol. 13:981-1012 (1982)). Ulcerative colitis typically involves the rectum and extends proximally without intervening uninvolved "skip" areas which are usually the hallmarks of Crohn's disease. The histologic features of active ulcerative colitis include, beside the superficial ulcers, infiltration by inflammatory cells (e.g., mainly lymphocytes, plasma cells, variable number of neutrophils, eosinophils and mast cells) involving extensively the lamina propria. Crypt abscesses, i.e., aggregates of neutrophils near and invading the crypt epithelium are reliable indicators of activity, while depletion of mucin in goblet cells is a less frequent finding. Web site: http://www.delphion.com/details?pn=US05214066__ •

Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation Inventor(s): Raz; Eyal (Del Mar, CA), Rachmilewitz; Daniel (Tel Aviv, IL) Assignee(s): Tel Aviv Sourasky Medical Center (Tel Aviv, IL), The Regents of the University of California (Oakland, CA) Patent Number: 6,613,751 Date filed: February 22, 2001 Abstract: The invention provides a method for ameliorating gastrointestinal inflammation, particularly chronic gastrointestinal inflammation such as inflammatory bowel disease (IBD), in a subject. In one embodiment, the method comprises administering an immunomodulatory nucleic acid to a subject suffering from or susceptible to gastrointestinal inflammation. Excerpt(s): The invention relates to a method for ameliorating inflammation of the gastrointestinal tract, such as that associated with inflammatory bowel disease, in a subject. The method involves administering a nucleic acid comprising an immunomodulatory nucleotide sequence to the subject. The immunomodulatory sequence can be administered alone or together with an additional therapeutic agents.... Gastrointestinal inflammation is one of the most common types of inflammatory process which affects humans (for a review, see, e.g., Bamford, FEMS Immunol Med Microbiol (1999) 24(2):161-8). Inflammatory bowel disease (IBD), a form of chronic gastrointestinal inflammation, includes a group of chronic inflammatory disorders of generally unknown etiology, e.g., ulcerative colitis (UC) and Crohn's disease (CD). Clinical and experimental evidence suggest that the pathogenesis of IBD is multifactorial involving susceptibility genes and environmental factors (Sartor Am J Gastroenterol. (1997) 92:5S11S). The interaction of these factors with the immune system leads to intestinal inflammation and dysregulated mucosal immunity against commensal bacteria, various microbial products (e.g., LPS) or antigens (Mayer et al. Current concept of IBD: Etiology and pathogenesis. In "Inflammatory Bowel Disease" 5.sup.th edition 2000, Kirsner J B

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editor. W. B. Sanunders Company, pp 280-296; for a discussion of IBD in children see, e.g., Walker-Smith, Postgrad Med J (2000) 76(898):469-72).... Human Crohn's disease (CD) is thought to be characterized by type 1 Helper T (Th-1) response, which produce the cytokines interleukin IL-2, interferon.gamma., and tumor necrosis factor TNF (for a review of anti-TNF.alpha. therapy in Crohn's disease, see, e.g., Mikula Gastroenterol Nurs. (1999) 22(6):245-8; Selby, Vet Microbiol (2000) 77(3-4): 505-511). Ulcerative colitis (UC) is dominated by type 2 Helper T (Th-2) response which produce anti-inflammatory cytokines such as IL-4, IL-5 and IL-10. However, the demarcation between Th-1 and Th2 response in CD and UC is not an "all or none" response and it seems that there is significant overlap. Web site: http://www.delphion.com/details?pn=US06613751__ •

Method of treating inflammatory bowel disease Inventor(s): Panetta; Jill A. (Zionsville, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,552,439 Date filed: September 29, 1993 Abstract: Provided is a method for treating inflammatory bowel disease in mammals utilizing certain phenol and benzamide compounds. Excerpt(s): Mammals, both humans and animals, are known to suffer from various conditions involving inflammation of the bowels. Such conditions are typically characterized by unpleasant symptoms such as diarrhea, cramping and loss of appetite. Certain of the conditions, in particular ulcerative colitis, are also characterized by patches of ulceration. Accordingly, there is a need for a safe drug which will decrease the severity of bowel inflammation and alleviate the symptoms associated therewith.... The method of the present invention employs certain phenols and benzamides of the general formula set forth above. Such compounds are known in the art and have been found to possess various utilities.... U.S. Pat. No. 3,305,483 discloses that certain phenols of the above formula can be used as an antioxidant for various substances such as gasoline, diesel fuel, heating oil, lubricating oil, asphalt, petroleum wax and high molecular weight hydrocarbon polymers. Chemical Abstracts, 97, 200429 m (1982) teaches that 4-(2-dimethylaminoethyl)-2,6-di-t-butylphenol can be used as an antioxidant for jet aircraft fuel. European Patent Application 42,589 describes the use of various of the above phenols as antioxidants for polymeric norbornene type materials. Web site: http://www.delphion.com/details?pn=US05552439__

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Method of treating inflammatory bowel disease with tributyrin Inventor(s): Wu; Gary D. (Ardmore, PA) Assignee(s): Trustees of the Univ. of Penna () Patent Number: 5,569,680 Date filed: February 13, 1995 Abstract: A method for treating inflammatory bowel disease in a patient by inhibiting the production of interleukin-8 in intestinal epithelial cells by administering to said patient an enema of an effective amount of tributyrin.

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Excerpt(s): Short chain fatty acids (SCFA) are normal products of anaerobic bacterial fermentation of carbohydrates in the colon and are the major energy source for the colonic epithelium. Approximately 90% of the total SCFA content in the colon is composed of acetic, propionic, and n-butyric acids. Cummings, J. H. Lancet (1983) 1:1206-1209; Roediger, W. Gut (1980) 21:793-798; Roediger, W. Gastroenterology (1982) 83:424-429. It has been suggested that a lack of luminal SCFAs leads to mucosal atrophy in the short term and nutritional colitis after prolonged periods. Roediger, W. Dis. Col. and Rectum (1990) 33:858-862. This is particularly evident in diversion colitis which develops after diversion of the fecal stream and resolves with restoration of colorectal continuity. Glotzer et al. Gastroenterology (1981) 80:438-441. SCFA enemas have been shown to be effective in the treatment of diversion colitis. Harig et al. N. Engl. J. Med. (1989) 320:23-28.... It is not known whether or not ulcerative colitis has the same cause as diversion colitis. While some investigators have shown that SCFA levels are decreased in the stool of patients with ulcerative colitis (Vernia et al. Dig. Dis. Sci. (1988) 33:13531358) and that mitochondrial fatty acid oxidation is abnormal in colon cells isolated from patients with active disease (Roediger, W. Lancet (1980) 2:712-715), it is not known whether these alterations are responsible for or a result of active ulcerative colitis. The histologic appearance of active ulcerative colitis includes an intense lymphoplasmocytosis limited to the mucosa and submucosa often notable for a neutrophilic infiltrate invading the colonic epithelium, referred to as a crypt abscess. Ulcerative colitis may be, therefore, classified as a disorder of the colonic mucosa. Several investigators have shown that the colonic epithelium is in a hyperproliferative state with the expansion of the proliferative compartment from the lower crypt to the upper crypt extending to the surface epithelium of the colon. Biasco et al. Cancer Res. (1984) 44:5450-5454; Serafini et al. Gut (1981) 22:648-652. This proliferative state is independent of the degree of inflammation as well as the duration of disease and exists even when the disease is in a quiescent state. These findings suggest an intrinsic abnormality of the colonic epithelium in ulcerative colitis. Similar hyperproliferative states have been observed in patients at risk for colonic malignancy such as in familial polyposis coli, sporadic colon adenomas and familial nonpolyposis colon cancer. Risio, M. J. Cell Biochem. (1992) 16G:79-87.... Butyrate enemas have been used to reduce inflammation in patients with distal ulcerative colitis. Breuer et al. Dig. Dis. Sci. (1991) 36:185-187; Scheppach et al. Gastroenterology (1992) 103:51-56; Steinhart et al. Am. J. Gastro. (1994) 89:179-183. In two studies, butyrate enemas were shown to result in a significant clinical response in patients whose disease did not respond to traditional forms of treatment including use of corticosteroids and 5-amino salicylic acid compounds. The basis of this response is unknown. Scheppach et al. observed that the labeling index of clonocytes in the upper crypt of patients with ulcerative colitis fell to that of normal healthy controls after treatment with butyrate enemas. Irrigation of the colon with short chain fatty acids also resulted in improvement in patients with diversion colitis. However, the use of butyrate enemas in these diseases is severely limited due to its extremely strong odor which leads to patients refusing to continue treatment. Web site: http://www.delphion.com/details?pn=US05569680__

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Methods and compositions for treating inflammatory bowel disease Inventor(s): Borody; Thomas Julius (144 Great North Rd., Five Dock, AU 2046) Assignee(s): none reported Patent Number: 6,551,632 Date filed: July 6, 2001 Abstract: The present invention provides a method and composition of medications used to treat inflammatory bowel disease. The invention further provides combinations of anti-atypical mycobacterial agents effective against the atypical mycobacterial strains. It also provides a method of potentiating the anti-atypical mycobacterial agents in treatment of inflammatory bowel disease by immunizing patients with extracts of nonpathogenic mycobacteria. Excerpt(s): The invention relates to compositions and methods for the treatment of inflammatory bowel disease, such as Crohn's disease.... Inflammatory bowel disease (IBD) is a disorder of unknown aetiology characterised typically by diarrhoea, cramping, abdominal pains, weight loss and rectal bleeding. It encompasses such disorders as Crohn's disease, ulcerative colitis, indeterminate colitis, microscopic colitis and collagenous colitis. Its cause is unknown. However, in the past there has been some evidence that Mycobacterium paratuberculosis (Mp) and perhaps its various substrains, may play an infective role by entering the cells which make up the bowel wall. The source of this bacterium is unclear but may reside in other animals such as sheep, cattle, rabbits, as well as other humans. It may be transmitted to people perhaps via milk, contaminated water supplies, poorly cooked meat, etc. Although there has been long-standing controversy about the involvement of Mp in causation of Crohn's disease, recent applications of PCR usage are beginning to confirm that most Crohn's cases are indeed infected with this organism which is likely to be the causal infective agent. In the past, therapy directed at the eradication of Mp by using combined anti-TB drugs eg INH, pyrazinamide, streptomycin, ethambutol, rifampicin and PAS have been generally of little help to patients. In other words, although transient improvements in a proportion of patients did occur, no patient was cured. In fact, even if Mp had been the cause of this disease there was no effective therapy available for Mp since it was an "atypical mycobacterium" and for atypical mycobacteria there was no known therapy. Furthermore, since Mycobacterium paratuberculosis has a long division time multiple antimicrobial drugs are required to the treat the infection which has to be carried out for a long period of time--akin to the treatment used in the therapy of Mycobacterium tuberculosis. Furthermore, Mycobacterium tuberculosis therapy with the current drugs results in resistant strains forming. Such resistant strains do not become eradicated with known antimicrobial agents. Hence, there is no known effective cure for resistant TB.... Accordingly, there is a need for an effective treatment of inflammatory bowel disease, and in particular Crohn's disease. It is an object of this invention to provide such a treatment. Web site: http://www.delphion.com/details?pn=US06551632__

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Methods for treating inflammatory bowel disease Inventor(s): Moretti; Itagiba G. (Rua Dep. Nilson Ribas, 1012, Londrina, BR) Assignee(s): none reported Patent Number: 6,114,382 Date filed: November 11, 1998 Abstract: The present invention provides novel compositions and methods relating to the treatment of Inflammatory Bowel Disease ("IBD"), most notably, Ulcerative Colitis, Crohn's Disease, Colitis and Diverticulitis. The invention relates to the discovery of a parasitic microsporidia infecting the epithelium cells lining the gastrointestinal tract of patients suffering from IBD. The discovery of this correlation between the disease and the microsporidia, described herein, led to the development of methods for the accurate diagnosis of patients suffering from IBD, and also of methods for treating such a patient in accordance with the invention. This discovery also provides for the development of animal models to further elucidate the mechanism of the disease and potential additional cures therefor. The present invention, in a preferred aspect, provides treatment methods wherein a patient suffering from a microsporidia infection is administered a pharmaceutically-effective amount of a N,N'-di-[halogenated-(lower alkanoyl)]-diamine compound. Excerpt(s): The invention relates generally to research directed to, and medical treatment of, Inflammatory Bowel Disease ("IBD"). More specifically, the invention relates to the discovery of a correlation between IBD and an intestinal parasitic microsporidia infection. The invention therefore involves, in preferred aspects, methods for diagnosing IBD or other microsporidia infection, and methods for treating a patient, preferably a human patient, having IBD or other microsporidia infection. More particularly, the invention relates in preferred aspects to the use of pharmaceuticallyactive compounds for treating a patient suffering from IBD.... Inflammatory bowel disease (IBD) is a group of chronic disorders that cause inflammation and/or ulceration in the small and large intestines. Most often, IBD is classified as ulcerative colitis or Crohn's disease, but may be referred to as diverticulitis, colitis, enteritis, ileitis, and proctitis. Ulcerative colitis has also been commonly referred to as "unspecific ulcerative colitis" or "idiopathic ulcerative colitis" because physicians and scientists have been unsuccessful in their attempts to identify the etiological agent causing the disease. Ulcerative colitis causes ulceration and/or inflammation of the inner lining of the colon and rectum, while Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. Crohn's disease may involve any segment of the digestive tract, including the mouth, esophagus, stomach, and small intestine, although characteristically the region of greatest involvement is the distal one-quarter of the small intestine and the proximal colon. Ulcerative colitis is typically isolated in the proximity of the colon. Ulcerative colitis and Crohn's disease cause similar symptoms that often resemble other conditions, such as irritable bowel syndrome (spastic colitis); therefore, the correct diagnosis may take some time, and is certainly not straightforward.... In ulcerative colitis, the inner lining of the large intestine (colon or bowel) and rectum become inflamed. The inflammation usually begins in the rectum and lower (sigmoid) intestine and spreads upward to the entire colon. Ulcerative colitis rarely affects the small intestine; however, the lower section, the ileum, is sometimes involved. The inflammation causes the colon to empty frequently, resulting in diarrhea. As cells on the surface of the lining of the colon die and slough off, ulcers (tiny open sores) form, causing pus, mucus and bleeding. Because ulcerative colitis is associated with mucosal injury, it is desirable to detect ulcerative colitis early in the patient's life, and to be able to

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distinguish ulcerative colitis from functional disorders such as irritable bowel syndrome. Early intervention can improve the long-range prognosis for the patient. Web site: http://www.delphion.com/details?pn=US06114382__ •

Methods for treating inflammatory bowel disease with leukotriene synthesis inhibitors Inventor(s): Marshall; Paul J. (Madison, CT), Wood; David D. (Wilton, CT), NickersonNutter; Cheryl L. (Milford, CT), Muller-Peddinghaus; Reiner (Bergisch-Gladbach, DE) Assignee(s): Miles Inc. (West Haven, CT) Patent Number: 5,391,555 Date filed: February 26, 1993 Abstract: Described are methods for ameliorating symptoms associated with inflammatory bowel disease such as ulcerative colitis and Crohn's disease (regional enteritis) with four specific quinoline leukotriene synthesis inhibitors. Excerpt(s): The invention relates to methods for ameliorating symptoms associated with inflammatory bowel disease. More particularly, methods for use of four specific quinoline leukotriene synthesis inhibitors for treating ulcerative colitis and Crohn's disease (regional enteritis) are disclosed.... The clinical manifestations of ulcerative colitis and Crohn's disease share the common feature of inflammation. In ulcerative colitis the earliest lesion is an inflammatory infiltration with abscess formation at the base of the crypts of Lieberkuhn. Coalescence of these distended and ruptured crypts tends to separate the overlying mucosa from its blood supply, leading to ulceration. The inflammatory involvement is diffuse and superficial, usually limited to the mucosa and submucosa.... The clinical picture includes cramping, lower abdominal pain or rectal bleeding, soon followed by frequent, loose discharges consisting mainly of blood, pus, and mucus with scanty fecal particles. The rectum and ampulla are usually found to be spastic. Web site: http://www.delphion.com/details?pn=US05391555__

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Peptide T and related peptides in the treatment of inflammation, including inflammatory bowel disease Inventor(s): Rathjen; Deborah (New South Wales, AU), Widmer; Fred (New South Wales, AU), MacFadden; Douglas Kevin (Ontario, CA), Doob; Penelope Reed (Ontario, CA), Carlen; Peter Louis (Ontario, CA), Aston; Roger (Wiltshire, GB2), Andersen; Anders Jorgen (Kokkedal, DK), Phipps; David James (Ontario, CA) Assignee(s): Peptide Technology Limited (Dee Why, AU), Drug Royalty Corporation (New South Wales, AU) Patent Number: 5,756,449 Date filed: February 24, 1995 Abstract: A method of treating inflammatory bowel disease in patients in need of such treatment by administering an effective amount of: I-A-B-C-D-E-F-G-H-II (General Formula I), wherein A is Ala, Gly, Val, Ser, Thr or absent, B is Ala, Gly, Val, Ser, Thr, or absent, C is Ser, Thr or absent. D is Ser, Thr, Asn, Glu, Arg, IIe, Leu or absent, E is Ser, Thr, Asp or absent, F is Ser, Thr, Asp or absent, G is Tyr or absent, H is Thr, Arg, Gly,

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Met, Met(O), Cys, Thr, Gly or absent, and I is Cys or absent II is Cys, an amide group, substituted amid group, an ester group or absent. At least one of the amino acids optionally being substituted by a monomeric or polymeric carbohydrate or derivative thereof, such substitution being accomplished through hydroxyl and/or amino and/or amido groups of the amino acids, and wherein the peptide comprises at least 4 amino acid residues, and a pharmaceutically acceptable salt thereof. Excerpt(s): This application is a 371 of PCT/GB93/00649, filed Mar. 29, 1993.... The present invention relates, broadly, to the treatment of prevention of inflammation, whether caused by bacteria, viruses and/or other infective agents, opportunistic infections (which may be consequent on an immunodepressed state, for example resulting from cancer or therapy, particularly cytotoxic drug therapy or radiotherapy) autoimmunity or otherwise. In particular embodiments, the invention relates to the prevention or treatment of neurodegenerative or demyelinating diseases such as HTLV1-associated myelopathy (HAM), multiple sclerosis (MS) and symptoms or diseases in humans which are associated with chromatic immune activation. The invention also relates to pharmaceutical compositions useful in such treatment and/or prevention and to certain active peptides per se.... Septic shock is an illustration of a disease involving inflammation. Many of the clinical features of Gram-negative septic shock may be reproduced in animals by the administration of lipopolysaccharide (LPS). The administration of LPS to animals can prompt severe metabolic and physiological changes which can lead to death. Associated with the injection of LPS is the extensive production of tumour necrosis factor alpha (TNF-.alpha.). Mice injected with recombinant human TNF develop piloerection of the hair (ruffling), diarrhoea and a withdrawn and unkempt appearance followed by death if sufficient amounts are given. Rats treated with TNF become hypotensive, tachypneic and die of sudden respiratory arrest (Tracey et al, 1986 Science 234, 470). Severe acidosis, marked haemoconcentration and biphasic changes in blood glucose concentration were also observed. Web site: http://www.delphion.com/details?pn=US05756449__ •

Prednisolone metasulphobenzoate preparation for the treatment of inflammatory bowel disease Inventor(s): Speirs; Christopher J. (82 Lower Road, Fetcham, Leatherhead, Surrey KT22 9NG, GB) Assignee(s): none reported Patent Number: 5,834,021 Date filed: February 11, 1997 Abstract: The dissolution at pH 6.5 of prednisolone metasulphobenzoate or a pharmacologically acceptable salt thereof from a non-disintegratable solid enteric composition comprising the prednisolone metasulphobenzoate in an excipient matrix is increased by the presence in the matrix of a rheological modifying agent, especially croscarmellose, in an amount of at least 5 percent by weight of the composition but insufficient to cause disintegration. Preferably the composition is in the form of pellets coated with an enteric coating which is substantially insoluble below pH 7 and contained in a capsule or tablet coated with an enteric coating which is soluble at a pH in the range pH 5.5 to pH 7. The coated capsules and tablets are for use in the treatment of inflammatory bowel disease, especially ulcerative colitis and Crohn's disease.

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Excerpt(s): The present invention relates to the use of prednisolone metasulphobenzoate (11,17-dihydroxy-21-›(3-sulphobenzoyl) oxy! pregna-1,4-diene-3 20-dione) and pharmacologically acceptable salts thereof, especially the sodium salt, in the treatment of inflammatory bowel disease. In particular, it provides a solid enteric pharmaceutical composition having relatively rapid dissolution at pH 6.5 of the prednisolone metasulphobenzoate from an excipient matrix and dosage forms containing pellets (or granules) of the composition unless it is clear from the context that the free ester is intended, the terms "Prednisolone metasulphobenzoate" and "PRED-MSB" are used herein to include pharmacologically acceptable salts of prednisolone metasulphobenzoate as well as the free ester.... Steroids are widely used to treat severe cases of inflammation of the large bowel, especially ulcerative colitis and Crohn's disease. Usually, they are administered orally or parenterally to provide a systemic effect or rectally by enema to provide a topical effect. Relatively high doses of steroids are required to treat severe cases of inflammatory bowel disease. However, systemic absorption produces serious side effects and, although absorption is lower with rectal administration, the use of enemas is inconvenient.... The most commonly used steroid in the oral treatment of inflammatory bowel disease is prednisolone (17,21dihydroxypregna-1,4-diene-3, 11,20-trione) in the form of the free alcohol or an ester thereof, usually the acetate. Daily doses of 15 to 60 mg (calculated as the free alcohol) are required to treat severe cases of inflammatory bowel disease but absorption at these doses is harmful. Accordingly, present treatment with prednisolone is limited in both dosage and duration of therapy. Web site: http://www.delphion.com/details?pn=US05834021__ •

Prevention and treatment of inflammatory bowel disease Inventor(s): Stafford; Douglas C. (Madison, WI), Worledge; Katherine L. (Madison, WI), Kink; John A. (Madison, WI) Assignee(s): Promega Corporation (Madison, WI) Patent Number: 6,395,273 Date filed: June 10, 1998 Abstract: Methods are described for treating inflammatory bowel disease in animals, including humans. Specific avian polyclonal antibodies directed to TNF are shown to have a beneficial effect in animal models predictive of human therapy for the treatment of colitis. Excerpt(s): The present invention relates to therapeutics for the prevention and treatment of inflammatory bowel disease, and in particular the prevention and treatment of inflammatory bowel disease in humans as well as other animals through the use of avian polyclonal antibody therapy.... Inflammatory bowel diseases (IBD) are defined by chronic, relapsing intestinal inflammation of obscure origin. IBD refers to two distinct disorders, Crohn's disease and ulcerative colitis (IC). Both diseases appear to result from the unrestrained activation of an inflammatory response in the intestine. This inflammatory cascade is thought to be perpetuated through the actions of proinflammatory cytolines and selective activation of lymphocyte subsets. In patients with IBD, ulcers and inflammation of the inner lining of the intestines lead to symptoms of abdominal pain, diarrhea, and rectal bleeding. Ulcerative colitis occurs in the large intestine, while in Crohn's, the disease can involve the entire GI tract as well as the small and large intestines. For most patients, IBD is a chronic condition with symptoms lasting for months to years. It is most common in young adults, but can occur at any age. It is

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found worldwide, but is most common in industrialized countries such as the United States, England, and northern Europe. It is especially common in people of Jewish descent and has racial differences in incidence as well. The clinical symptoms of IBD are intermittent rectal bleeding, crampy abdominal pain, weight loss and diarrhea. Diagnosis of IBD is based on the clinical symptoms, the use of a barium enema, but direct visualization (sigmoidoscopy or colonoscopy) is the most accurate test. Protracted IBD is a risk factor for colon cancer, and treatment of IBD can involve medications and surgery.... Some patients with UC only have disease in the rectum (proctitis). Others with UC have disease limited the rectum and the adjacent left colon (proctosigmoiditis). Yet others have UC of the entire colon (universal IBD). Symptoms of UC are generally more severe with more extensive disease (larger portion of the colon involved with disease). Web site: http://www.delphion.com/details?pn=US06395273__ •

Stimulating neutrophil function to treat inflammatory bowel disease Inventor(s): Dieckgraefe; Brian (Chesterfield, MO), Korzenik; Joshua (St. Louis, MO) Assignee(s): The Washington University (St. Louis, MO) Patent Number: 6,500,418 Date filed: August 11, 2000 Abstract: Immune stimulatory amounts of hematopoietic colony stimulating factors are administered to patients with inflammatory bowel disease. The factors include G-CSF and GM-CSF. These factors induce and maintain remission of the disease and its manifestations, whether within the intestine or without. Excerpt(s): Crohn's disease persists as an enigma: without a deciphered etiology and without adequate therapy. Prevailing explanations of the pathogenesis of Crohn's disease (Crohn's Disease) hold that the characteristic chronic intestinal inflammation results from an aberrant, activated immune response generated against ubiquitous bacteria or bacterial products that gain access to the lamina propria, perhaps through a more permeable intestinal barrier. The abnormal reaction has been suggested to be mediated principally by T-cells enhanced by an intrinsic imbalance in pro-inflammatory and contra-inflammatory mediators. Thus, most therapy aims to counteract that inflammatory state with increasingly potent and sophisticated immune suppressants.... Current therapy, mostly directed at suppressing the inflammatory process, remains inadequate both for the treatment of flares and maintenance of remission. Steroids can be effective in short term use but produce dependency in a significant proportion of patients. While certain antibiotics appear promising, data are limited. Thus there is a need in the art for effective method for treating inflammatory bowel diseases.... It is an object of the invention to provide a method of treating Crohn's Disease. Web site: http://www.delphion.com/details?pn=US06500418__

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Treatment for inflammatory bowel disease with a vcam-1/1gG fusion protein Inventor(s): Burkly; Linda C. (West Newton, MA), Lobb; Roy R. (Westwood, MA) Assignee(s): Biogen, Inc. (Cambridge, MA) Patent Number: 6,482,409 Date filed: September 21, 1998 Abstract: A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of a VCAM-1/IgG fusion protein. Excerpt(s): The present invention relates to a treatment for inflammatory bowel disease (IBD). More particularly, this invention relates to the use of antibodies recognizing the integrin VLA-4 (very late antigen-4) in the treatment of IBD.... Inflammatory bowel disease, or IBD, is a collective term encompassing ulcerative colitis and Crohn's disease (ileitis), which are chronic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is confined to the large intestine (colon) and rectum, and involves only the inner lining of the intestinal wall. Crohn's disease may affect any section of the gastrointestinal tract (i.e., mouth, esophagus, stomach, small intestine, large intestine, rectum and anus) and may involve all layers of the intestinal wall. Both diseases are characterized by abdominal pain and cramping, diarrhea, rectal bleeding and fever. The symptoms of these diseases are usually progressive, and sufferers typically experience periods of remission followed by severe flareups.... Severe side effects are associated with the drugs commonly prescribed for IBD, including nausea, dizziness, changes in blood chemistry (including anemia and leukopenia), skin rashes and drug dependence; and the surgical treatments are radical procedures that often profoundly alter the everyday life of the patient. Accordingly, there is a great need for treatments for IBD that are effective yet less severe in their side effects and are less invasive of the IBD sufferer's body and quality of life. Web site: http://www.delphion.com/details?pn=US06482409__

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Treatment for inflammatory bowel disease with VLA-4 blockers Inventor(s): Lobb; Roy R. (Westwood, MA), Burkly; Linda C. (West Newton, MA) Assignee(s): Biogen, Inc. (Cambridge, MA) Patent Number: 5,932,214 Date filed: October 15, 1997 Abstract: A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of an antibody, polypeptide or other molecule recognizing VLA-4, a surface molecule expressed on most types of white blood cells and involved in leukocyte adhesion to endothelium and other tissus in the gut. Excerpt(s): The present invention relates to a treatment for inflammatory bowel disease (IBD). More particularly, this invention relates to the use of antibodies recognizing the integrin VLA-4 (very late antigen-4) in the treatment of IBD.... Inflammatory bowel disease, or IBD, is a collective term encompassing ulcerative colitis and Crohn's disease (ileitis), which are chronic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is confined to the large intestine (colon) and rectum, and involves only the inner lining of the intestinal wall. Crohn's disease may affect any section of the gastrointestinal tract (i.e., mouth, esophagus, stomach, small intestine, large intestine, rectum and anus) and may involve all layers of the intestinal wall. Both diseases are

Patents 277

characterized by abdominal pain and cramping, diarrhea, rectal bleeding and fever. The symptoms of these diseases are usually progressive, and sufferers typically experience periods of remission followed by severe flareups.... Severe side effects are associated with the drugs commonly prescribed for IBD, including nausea, dizziness, changes in blood chemistry (including anemia and leukopenia), skin rashes and drug dependence; and the surgical treatments are radical procedures that often profoundly alter the everyday life of the patient. Accordingly, there is a great need for treatments for IBD that are effective yet less severe in their side effects and are less invasive of the IBD sufferer's body and quality of life. Web site: http://www.delphion.com/details?pn=US05932214__ •

Treatment of inflammatory bowel disease Inventor(s): Rampton; David (London, GB), Panetta; Jill A. (Zionsville, IN), Ho; Peter P. K. (Carmel, IN), Blake; David (Droitwich, GB), Simmonds; Nicola (London, GB) Assignee(s): Eli Lilly and Company (Indianapolis, IN), London Hospital Medical College (London, GB2) Patent Number: 5,294,630 Date filed: July 7, 1992 Abstract: Inflammatory bowel disease is treated, and patients are protected from a relapse into active disease, by the administration of a compound chosen from a series of 3-phenyl-5-carboxypyrazoles and isothiazoles. Excerpt(s): The present invention belongs to the fields of pharmaceutical chemistry and gastroenterology, and provides a method of treating, or preventing the recurrence of, inflammatory bowel disease, and reducing the risk of cancer in inflammatory bowel disease, making use of a series of phenylpyrazoles and phenylisothiazoles.... Inflammatory bowel disease (IBD) comprises two conditions, ulcerative colitis (UC) and Crohn's disease (CD). Both UC and CD are chronic inflammatory diseases of the digestive tract, the former restricted to the large intestine and the latter affecting any part of the bowel from mouth to anus. The cause of both diseases is unknown, but increasing evidence points to a major pathogenic role for reactive oxygen metabolites.... The incidence of UC is about 5/100,000/year; that of CD is similar but rising. The prevalence of each disease is about 60/100,000. The diseases first present most commonly in the third decade, with a second peak of incidence at about 60-80 years. Both diseases occur world-wide, but may be more common in developed countries than in the Third World. Web site: http://www.delphion.com/details?pn=US05294630__

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Treatment of Inflammatory bowel disease by inhibiting binding and/or signalling through.alpha. 4.beta. 7 and its ligands and madcam Inventor(s): Picarella; Dominic (Boston, MA), Newman; Walter (Boston, MA), Ringler; Douglas J. (Revere, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (Cambridge, MA) Patent Number: 6,551,593 Date filed: February 10, 1995

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Abstract: The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM. Excerpt(s): Inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease, for example, can be a debilitating and progressive disease involving inflammation of the gastrointestinal tract affecting an estimated two million people in the United States. Symptoms include abdominal pain, cramping, diarrhea and rectal bleeding. IBD treatments have included anti-inflammatory drugs (such as, corticosteroids and sulfasalazine), immunosuppressive drugs (such as, 6mercaptopurine, cyclosporine and azathioprine) and surgery (such as, colectomy). Podolsky, The New England Journal of Medicine, 325:928-937 (1991) and Podolsky, The New England Journal of Medicine, 325:1008-1016 (1991).... Some studies have suggested that the cell adhesion molecule, ICAM-1, mediates leukocyte recruitment to inflammatory sites through adhesion to leukocyte surface ligands, i.e. Mac-1, LFA-1 or.alpha.4.beta.2 (Springer, Nature, 346:425-434 (1990)). In addition, vascular cell adhesion molecule-1 (VCAM-1), recognizing the.alpha.4.beta.1 integrin (VLA-4), has been reported to play a role in in vivo leukocyte recruitment as well (Silber et al., J. Clin. Invest. 93:1554-1563 (1994)). It has been proposed that IBD can be treated by blocking the interaction of ICAM-1 with LFA-1 or Mac-1 or VCAM-1 with.alpha.4.beta.1 (e.g., WO 93/15764). However, these therapeutic targets are likely involved in inflammatory processes in multiple organs, and a functional blockade would likely result in systemic immune dysfunction.... Mucosal addressin MAdCAM, a mucosal vascular adhesion molecule, is a 58-66K glycoprotein adhesion receptor for lymphocytes which is distinct from VCAM-1 and ICAM-1 (Briskin et al., Nature, 363:461-463 (1993)). In contrast to VCAM-1 and ICAM-1, MAdCAM is preferentially expressed in the gastrointestinal tract, binds the.alpha.4.beta.7 integrin (also called LPAM-1 and CD49d/CD.sup.-) found on lymphocytes, and participates in the homing of these cells to mucosal sites, such as Peyer's patches in the intestinal wall (Hamann et al., Journal of Immunology, 152:32823293 (1994)). The use of inhibitors to the binding of MAdCAM to the receptor,.alpha.4.beta.7, in the treatment of diseases such as IBD has not been suggested. Web site: http://www.delphion.com/details?pn=US06551593__ •

Treatment of inflammatory bowel disease using oral dosage forms of omega-3 polyunsaturated acids Inventor(s): Camporesi; Emilio P. (Ziefen, CH), Buser; Thomas (Ziefen, CH) Assignee(s): Tillotts Pharma AG (Ziefen, CH) Patent Number: 5,948,818 Date filed: April 30, 1998 Abstract: Inflammatory bowel disease, especially Crohn's disease and ulcerative colitis, is treated by administration of an oral dosage form, containing as an active principle an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof, which releases the acid in the ileum. Preferably the oral dosage form is a gelatine capsule coated with a poly(ethylacrylate-methylmethacrylate).

Patents 279

Excerpt(s): The present invention relates to the oral administration of omega-3 polyunsaturated acids especially, but not exclusively, eicosapenta-5,8,11,14,17-enoic acid ("EPA") and/or docosahexa-4,7,10,13,16,19-enioc acid ("DHA"). In particular, it provides enteric dosage forms of omega-3 polyunsaturated acids for the treatment of inflammatory bowel disease especially, but not exclusively, Crohn's disease and ulcerative colitis.... It is known that DHA, EPA and other omega-3 polyunsaturated acids are of use in the treatment of inflammatory bowel disease (see, for example, EP-A0244832, EP-A-0289204, EP-A-0311091 & WO-A-93/21912).... Enteric coated products containing DHA or EPA have been reported for use in the treatment of other conditions (see EP-A-0336662, GB-A-2090529, JP-A-62201823, & WO-A-90/04391). Web site: http://www.delphion.com/details?pn=US05948818__ •

Treatment of inflammatory bowel disease with IFN-.gamma. inhibitors Inventor(s): Ashkenazi; Avi J. (San Mateo, CA), Ward; Rebecca H. R. (San Francisco, CA) Assignee(s): Genentech, Inc. (South San Francisco, CA) Patent Number: 6,558,661 Date filed: February 22, 1994 Abstract: The invention concerns a method for the prevention or treatment of inflammatory bowel disease by administering an interferon-.gamma. inhibitor. The invention further concerns pharmaceutical compositions and bispecific molecules useful in such method. Excerpt(s): The invention concerns the prevention or treatment of inflammatory bowel disease by administering an interferon-gamma (IFN-.gamma.) inhibitor.... Inflammatory bowel disease (IBD) is a collective term for ulcerative colitis (UC) and Crohn's disease, which are considered as two different entities, but have many common features and probably share at least some pathologic mechanisms. There is sufficient overlap in the diagnostic criteria for UC and CD that it is sometimes impossible to say which a given patient has; however, the type of lesion typically seen is different, as is the localization. UC mostly appears in the colon, proximal to the rectum, and the characteristic lesion is a superficial ulcer of the mucosa; CD can appear anywhere in the bowel, with occasional involvement of stomach, esophagus and duodenum, and the lesions are usually described as extensive linear fissures.... The aetiology of these diseases is unknown and the initial lesion has not been clearly defined; however, patchy necrosis of the surface epithelium, focal accumulations of leukocytes adjacent to glandular crypts, and an increased number of intraepithelial lymphocytes and certain macrophage subsets have been described as putative early changes, especially in Crohn's disease. Web site: http://www.delphion.com/details?pn=US06558661__

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Use of biologically active vitamin D compounds for the prevention and treatment of inflammatory bowel disease Inventor(s): Nashold; Faye E. (Sun Prairie, WI), Hayes; Colleen E. (Madison, WI) Assignee(s): Northern Lights Pharmaceuticals, LLC (Madison, WI) Patent Number: 6,358,939 Date filed: December 21, 1999

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Abstract: Methods of treating inflammatory bowel disease are described, and in particular the prevention and treatment of inflammatory bowel disease in humans as well as other animals. These methods involve the administration of biologically active vitamin D compounds, and therapeutic compositions thereof, so that the symptoms of Inflammatory Bowel Disease are reduced or relieved. Excerpt(s): The present invention relates to therapeutics for the prevention and treatment of inflammatory bowel disease, and in particular the prevention and treatment of inflammatory bowel disease in humans as well as other animals through the use of biologically active vitamin D compounds.... Inflammatory bowel diseases (IBD) are defined by chronic, relapsing intestinal inflammation of obscure origin. IBD refers to two distinct disorders, Crohn's disease and ulcerative colitis (UC). Both diseases appear to involve either a dysregulated immune response to GI tract antigens, a mucosal barrier breach, and/or an adverse inflammatory reaction to a persistent intestinal infection. The GI tract luminal contents and bacteria constantly stimulate the mucosal immune system, and a delicate balance of proinflammatory and antiinflammatory cells and molecules maintains the integrity of the GI tract, without eliciting severe and damaging inflammation [MacDermott, R. P., J Gastroenterology, 31:907:-916 (1996)]. It is unknown how the IBD inflammatory cascade begins, but constant GI antigen-dependent stimulation of the mucosal and systemic immune systems perpetuates the inflammatory cascade and drives lesion formation.... There is no known cure for IBD, which afflicts 2 million Americans. Current methods of managing IBD symptoms cost an estimated $1.2 billion annually in the United States alone. Web site: http://www.delphion.com/details?pn=US06358939__ •

Use of cytokine restraining agents to treat inflammatory bowel disease Inventor(s): Tuttle; Ronald R. (Escondido, CA), Girten; Beverly E. (San Diego, CA) Assignee(s): Trega Biosciences, Inc. (San Diego, CA) Patent Number: 5,888,969 Date filed: July 14, 1997 Abstract: The present invention relates to the use of cytokine restraining agents to treat inflammatory bowel disease. Excerpt(s): This invention relates generally to the fields of peptide chemistry and molecular pathology and, more specifically, to novel cytokine restraining agents.... Cytokines are a class of proteins produced by macrophages and monocytes in response to viral or bacterial infection and in response to T cell stimulation during an immune response. Cytokines are normally present in very low concentrations in a tissue and mediate their effects through binding to high affinity receptors on specific cell types.... Various cytokines such as the interleukins (IL), interferons (IF) and tumor necrosis factor (TNF) are produced during immune and inflammatory responses and control various aspects of these responses. Following induction of an immune or inflammatory response, the concentrations of the various cytokines increase at different times. For example, following exposure of a subject to bacterial endotoxin, TNF and interleukin-6 (IL6) levels increase, followed a few hours later by increases in the levels of IL-1 and IL8. Web site: http://www.delphion.com/details?pn=US05888969__

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Use of IL-10 to treat inflammatory bowel disease Inventor(s): Rennick; Donna (Los Altos, CA) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 5,368,854 Date filed: August 20, 1992 Abstract: The invention provides in vivo methods and compositions for using IL-10 to treat inflammatory bowel disease in a mammal. The method comprises administering to the mammal an effective amount of IL-10, preferably intravascularly, alone or in combination with other therapeutic reagents. Excerpt(s): The invention relates generally to manipulation of the human immune response to ameliorate or alter signs or symptoms of inflammatory conditions or diseases relating to inflammation, immunity, or autoimmunity. More specifically, the invention relates to treatment of inflammatory bowel disease using interleukin-10 (IL10).... The immune system is diverse and complex. It includes a multitude of natural and adaptive immune mechanisms and reactions. For practical purposes, the immune system is often thought of in terms of either humoral and cellular immune responses. Humoral immunity refers broadly to antibody production and actions by B-cells including plasma cells. Cellular immunity is mediated by cells including T-cells, monocytes, macrophages and histiocytes. T-cells and B-cells are two broad categories of lymphocytes. T-cells may be further categorized according to their various functions or markers. For instance, T-cells can be classified as T helper cells or T suppressor cells. Additionally, T-cells can be activated to become cytotoxic or to perform other more specialized functions. Normally, T-cells and B-cells have interactions that may regulate each other's activity to some extent. See, e.g., Paul (ed.) Fundamentals of Immunology (2d ed.) Raven Press, New York (1989).... For instance, for different antigens either cellular or humoral responses may predominate, typically, in a mutually exclusive fashion. The severity of some diseases, e.g., leprosy, leishmaniasis, and some types of autoimmunity, may be due the inappropriate dominance of one class of response over the other. Mosmann et al., Immunol. Today 8:223-227 (1987); Mosmann et al., Ann. Rev. Immunol. 7:145-173 (1989); Parish, Transplant. Rev 13:35-66 (1972); and Liew, Immunol. Today 10:40-45 (1989). Web site: http://www.delphion.com/details?pn=US05368854__

Patent Applications on Crohn’s Disease 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 Crohn’s disease:

10

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

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Method and composition for the treatment of inflammatory bowel disease Inventor(s): Schwartz, Marshall Z. (Bryn Mawr, PA) Correspondence: McGuire Woods LLP; 1750 Tysons Boulevard, Suite 1800; McLean; VA; 22102; US Patent Application Number: 20020013265 Date filed: August 17, 2001 Abstract: The present invention relates to a method and composition for treating a patient having a condition characterized as inflammatory bowel disease with an effective dose of HGF. Mucosal damage and histologic lesions are reduced by administering HGF to patients suffering from the same. HGF may be administered to the patient lumenally or systemically. Excerpt(s): This application is a continuation-in-part of application Ser. No. 08/932,391, filed on Sep. 17, 1997.... The present invention relates broadly to the treatment of inflammatory bowel diseases in a patient. More particularly, the invention relates to treating a patient having an inflammatory bowel disease condition with Hepatocyte Growth Factor ("HGF").... Chronic Ulcerative Colitis ("CUC") and Crohn's Disease ("CD"), generally referred to as Inflammatory Bowel Disease ("IBD"), are devastating disorders with an unknown etiology. Current medical therapy can control symptomatic exacerbations of IBD, but does not provide a cure. Progress in understanding the pathogenesis of IBD has been slowed by the lack of availability of animal models that exhibit the chronic, spontaneous, relapsing gastrointestinal ("GI") inflammation that is symptomatic of human IBD. Numerous murine and rat experimental models exist that possess some but not all of the features of human IBD. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for differentiating irritable bowel syndrome from inflammatory bowel disease (IBD) and for monitoring persons with IBD using total endogenous lactoferrin as a marker Inventor(s): Guerrant, Richard Littleton; (Charlottesville, VA), Wilkins, Tracy Dale; (Riner, VA), Boone, James Hunter; (Christiansburg, VA), Lyerly, David Maxwell; (Radford, VA) Correspondence: SHOOK, HARDY & BACON L.L.P. 1200 Main Street; Kansas City; MO; 64105-2118; US Patent Application Number: 20020168698 Date filed: November 14, 2001 Abstract: A method for aiding in differentiating irritable bowel syndrome from inflammatory bowel disease by determining the level of total endogenous human lactoferrin in clinical specimens, such as feces, mucus and bile, wherein an elevated level of lactoferrin substantially precludes diagnoses of IBS and other noninflammatory etiologies, and a kit usable in such method are provided. Further provided is a method for quantitating the level of total endogenous human lactoferrin in clinical specimens, such as feces, mucus and bile, to monitor gastrointestinal inflammation in persons having inflammatory bowel disease. Excerpt(s): Pursuant to 35 U.S.C. Section 119(e), this application claims the benefit of U.S. provisional application Serial No. 60/248,288; filed Nov. 14, 2000 entitled "Method

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for Differentiating Irritable Bowel Syndrome (IBS) From inflammatory Bowel Disease (IBD) by Measuring Fecal Lactoferrin Levels as an Indicator of Gastrointestinal Inflammation" the entirety of the disclosure of which is hereby specifically incorporated by reference.... Not Applicable.... The present invention relates to the clinical differentiation and monitoring of gastrointestinal illnesses. More particularly, the present invention relates to a method for aiding in differentiating irritable bowel syndrome from inflammatory bowel disease by determining the level of total endogenous human lactoferrin in clinical specimens, such as feces, mucus and bile, wherein an elevated level of lactoferrin substantially precludes diagnoses of IBS and other noninflammatory etiologies, and a kit usable in such method. The present invention further relates to a method for quantitating the level of total endogenous human lactoferrin in clinical specimens, such as feces, mucus and bile, to monitor gastrointestinal inflammation in persons having inflammatory bowel disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation Inventor(s): Rachmilewitz, Daniel; (Tel Aviv, IL), Raz, Eyal; (Del Mar, CA) Correspondence: BOZICEVIC, FIELD & FRANCIS LLP; 200 MIDDLEFIELD RD; SUITE 200; MENLO PARK; CA; 94025; US Patent Application Number: 20030176389 Date filed: April 11, 2003 Abstract: The invention provides a method for ameliorating gastrointestinal inflammation, particularly chronic gastrointestinal inflammation such as inflammatory bowel disease (IBD), in a subject. In one embodiment, the method comprises administering an immunomodulatory nucleic acid to a subject suffering from or susceptible to gastrointestinal inflammation. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/184,256, filed Feb. 23, 2000, which application is incorporated herein by reference in its entirety.... The invention relates to a method for ameliorating inflammation of the gastrointestinal tract, such as that associated with inflammatory bowel disease, in a subject. The method involves administering a nucleic acid comprising an immunomodulatory nucleotide sequence to the subject. The immunomodulatory sequence can be administered alone or together with an additional therapeutic agents.... Gastrointestinal inflammation is one of the most common types of inflammatory process which affects humans (for a review, see, e.g., Bamford, FEMS Immunol Med Microbiol (1999) 24(2):161-8). Inflammatory bowel disease (IBD), a form of chronic gastrointestinal inflammation, includes a group of chronic inflammatory disorders of generally unknown etiology, e.g., ulcerative colitis (UC) and Crohn's disease (CD). Clinical and experimental evidence suggest that the pathogenesis of IBD is multifactorial involving susceptibility genes and environmental factors (Sartor Am J Gastroenterol. (1997) 92:5S11S). The interaction of these factors with the immune system leads to intestinal inflammation and dysregulated mucosal immunity against commensal bacteria, various microbial products (e.g., LPS) or antigens (Mayer et al. Current concept of IBD: Etiology and pathogenesis. In "Inflammatory Bowel Disease" 5.sup.th edition 2000, Kirsner JB editor. W. B. Sanunders Company, pp 280-296; for a discussion of IBD in children see, e.g., Walker-Smith, Postgrad Med J (2000) 76(898):469-72).

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

Methods and compositions for treating inflammatory bowel disease Inventor(s): Borody, Thomas Julius; (Five Dock, AU) Correspondence: JONES, TULLAR & COOPER, P.C. P.O. Box 2266 Eads Station; Arlington; VA; 22202; US Patent Application Number: 20020035075 Date filed: July 6, 2001 Abstract: The present invention provides a method and composition of medications used to treat inflammatory bowel disease. The invention further provides combinations of anti-atypical mycobacterial agents effective against the atypical mycobacterial strains. It also provides a method of potentiating the anti-atypical mycobacterial agents in treatment of inflammatory bowel disease by immunising patients with extracts of nonpathogenic mycobacteria. Excerpt(s): The invention relates to compositions and methods for the treatment of inflammatory bowel disease, such as Crohn's disease.... Inflammatory bowel disease (IBD) is a disorder of unknown aetiology characterised typically by diarrhoea, cramping, abdominal pains, weight loss and rectal bleeding. It encompasses such disorders as Crohn's disease, ulcerative colitis, indeterminate colitis, microscopic colitis and collagenous colitis. Its cause is unknown. However, in the past there has been some evidence that Mycobacterium paratuberculosis (Mp) and perhaps its various substrains, may play an infective role by entering the cells which make up the bowel wall. The source of this bacterium is unclear but may reside in other animals such as sheep, cattle, rabbits, as well as other humans. It may be transmitted to people perhaps via milk, contaminated water supplies, poorly cooked meat, etc. Although there has been long-standing controversy about the involvement of Mp in causation of Crohn's disease, recent applications of PCR usage are beginning to confirm that most Crohn's cases are indeed infected with this organism which is likely to be the causal infective agent, In the past, therapy directed at the eradication of Mp by using combined anti-TB drugs eg INH, pyrazinamide, streptomycin, ethambutol, rifampicin and PAS have been generally of little help to patients. In other words, although transient improvements in a proportion of patients did occur, no patient was cured. In fact, even if Mp had been the cause of this disease these was no effective therapy available for Mp since it was an "atypical mycobacteium" and for atypical mycobacteria there was no known therapy. Furthermore, since Mycobacterium paratuberculosis has a long division tine multiple antimicrobial drugs are required to the treat the infection which has to be carried out for a long period of time--akin to the treatment used in the therapy of Mycobacterium tuberculosis. Furthermore, Mycobacterium tuberculosis therapy with the current drugs results in resistant strains forming. Such resistant strains do not become eradicated with known antimicrobial agents. Hence, there is no known effective cure for resistant TB.... Accordingly, there is a need for an effective treatment of inflammatory bowel disease, and in particular Crohn's disease. It is an object of this invention to provide such a treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Oral immunoglobulin treatment for inflammatory bowel disease Inventor(s): Sundqvist, Tommy Eugen; (Linkoping, SE), Stenhammar, Lars Christian; (Linkoping, SE), Tjellstrom, Bo Arthur Einar; (Norrkoping, SE), Magnusson, Karl-Eric Ivan; (Linkoping, SE) Correspondence: SCULLY, SCOTT, MURPHY & PRESSER; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20020114802 Date filed: August 9, 2001 Abstract: The present invention provides a method of treating inflammatory bowel disease (IBD) in a patient in need thereof which comprises orally administering to the patient an effective amount of a pooled human polyclonal immunoglobulin preparation. The method allows treatment of mucosal inflammation from the luminal side of the gastrointestinal mucosa. Human immunoglobulin preparations suitable for use in the methods of the present invention may be made by any of the well-known methods used for preparing intravenous and intramuscular (parenteral) immunoglobulin preparations. Suitable immunoglobulin preparations may also be obtained commercially. The human immunoglobulin preparation may comprise any of the known immunoglobulin classes including IgA, IgG, IgM, IgE, and IgD. Preferably, the human immunoglobulin preparation comprises at least one of immunoglobulin G (IgG), immunoglobulin A (IgA) or a mixture of immunoglobulin G (IgG) and immunoglobulin A (IgA). Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/247,396, which claims priority from U.S. Provisional Application No. 60/074,193 filed on Feb. 10, 1998.... Inflammatory bowel disease (IBD) refers to serious, chronic disorders of the intestinal tract and specifically includes ulcerative colitis (UC) and Crohn's disease. IBD is often confused with irritable bowel syndrome (IBS). IBS refers to a wide spectrum of digestive problems ranging from common discomfort after eating, to diarrhea, constipation, alternating diarrhea and constipation, or any of these with abdominal pain. Lin Chang et al., 1994 IM-Internal Medicine (USA)15/2 (pp. 27-30, 3234). In IBS, unlike in IBD, there is no inflammatory component. In fact, examination of the tissues of the intestine and colon either by x-ray, scope, or biopsy reveals no abnormalities. The symptoms of IBS appear to be related to disturbances in gastrointestinal motility. While IBS is a serious condition, it is not an autoimmune disease as is IBD. Approximately 500,000 Americans are afflicted with IBD, and there are about 40,000 new cases of IBD diagnosed each year in the U.S. Although IBD encompasses both UC and Crohn's disease, the two diseases differ in their pathology. In UC, the inner lining of the large intestine (colon or bowel) and rectum becomes inflamed. Inflammation usually begins in the rectum and lower (sigmoid) intestine and spreads upward to the entire colon. UC rarely affects the small intestine except for the ileum. Patients suffering from Crohn's disease exhibit a different pattern of inflammation and ulceration. Crohn's disease often produces a patchy type of inflammation that is deeper into the intestinal wall than the superficial inflammation of UC. Furthermore, Crohn's disease can involve any portion of the digestive tract, including the small and large intestine, the stomach, and even the esophagus. The deeper inflammation of Crohn's disease leads to complications such as large hemorrhoids, rectal abscesses, or fistula that are not seen in UC.... The cause of IBD is unknown. Lofberg, R. (1997) J. Int. Med. 241:1-4. Many theories exist, but none have been proven. One leading theory suggests that some infectious agent, possibly a virus or bacterium, interacts with the immune system to trigger an inflammatory reaction in the

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intestinal wall. More recently, evidence has been mounting to support the role of genes in the development of the disease. Such evidence includes the increased chance of developing IBD in relatives of IBD patients, the clustering of the disease within families, the association of IBD with other genetic syndromes, and ethnic variations in disease frequencies. Since multiple genes are most likely involved with the development of IBD, it is difficult both to accurately predict which family members will develop IBD, and to identify the genes involved. Thus far, four chromosomal regions have been implicated as contributing to IBD susceptibility. Of these, a region of chromosome 16 has been confirmed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Stimulating neutrophil function to treat inflammatory bowel disease Inventor(s): Dieckgraefe, Brian; (Chesterfield, MO), Korzenik, Joshua; (St. Louis, MO) Correspondence: BANNER & WITCOFF; 1001 G STREET N W; SUITE 1100; WASHINGTON; DC; 20001; US Patent Application Number: 20030035801 Date filed: October 1, 2002 Abstract: Immune stimulatory amounts of hematopoietic colony stimulating factors are administered to patients with inflammatory bowel disease. The factors include G-CSF and GM-CSF. These factors induce and maintain remission of the disease and its manifestations, whether within the intestine or without. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/119,842 filed Feb. 12, 1999. The disclosure of the provisional application is expressly incorporated by reference herein.... Crohn's disease persists as an enigma: without a deciphered etiology and without adequate therapy. Prevailing explanations of the pathogenesis of Crohn's disease (Crohn's Disease) hold that the characteristic chronic intestinal inflammation results from an aberrant, activated immune response generated against ubiquitous bacteria or bacterial products that gain access to the lamina propria, perhaps through a more permeable intestinal barrier. The abnormal reaction has been suggested to be mediated principally by T-cells enhanced by an intrinsic imbalance in pro-inflammatory and contra-inflammatory mediators. Thus, most therapy aims to counteract that inflammatory state with increasingly potent and sophisticated immune suppressants.... Current therapy, mostly directed at suppressing the inflammatory process, remains inadequate both for the treatment of flares and maintenance of remission. Steroids can be effective in short term use but produce dependency in a significant proportion of patients. While certain antibiotics appear promising, data are limited. Thus there is a need in the art for effective method for treating inflammatory bowel diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment for inflammatory bowel disease (IBD) and related conditions Inventor(s): Basu, Amaresh; (San Diego, CA), Hoffman, Keith; (San Diego, CA) Correspondence: KNOBBE MARTENS OLSON & BEAR LLP; 620 NEWPORT CENTER DRIVE; SIXTEENTH FLOOR; NEWPORT BEACH; CA; 92660; US Patent Application Number: 20020025348 Date filed: June 5, 2001 Abstract: Compositions, including formulations, of plants for the treatment of Inflammatory Bowel Disease, Irritable Bowel Syndrome, and inflammatory and other related conditions, such as arthritis, are disclosed. The formulations consist of one or both of the two herbs Chen Pi (Citrus reticulata) and Wu Mei (Prunus mume), which, according to the invention, possess significant cytokine TNF-.alpha. inhibitory activity. The formulations also may include one or more of the following herbs which, according to the invention, inhibit PGE.sub.2: Hou Po (Magnoliae officinalis), Huang Bai (Phellodendron chinense), Huang Lian (Coptis chinensis), Huo Xiang (Agastaches rugosa), Pao Jiang (Zingiberis officinalis), Qin Pi (Fraxinus rynchophylla), and Zhi Gan Cao (Glycyrhizae inflata). Excerpt(s): The present application is a National Phase entry of PCT Application PCT/US00/34792, entitled "TREATMENT FOR INFLAMMATORY BOWEL DISEASE (IBD) AND RELATED CONDITIONS," and filed on Dec. 20, 2000, which claims priority from U.S. Provisional Application Serial No. 60/173,006, also entitled "TREATMENT FOR INFLAMMATORY BOWEL DISEASE (IBD) AND RELATED CONDITIONS," and filed on Dec. 23, 1999.... The present invention relates to novel formulations of plants and extracts thereof to be used for the treatment of bowel disorders. More specifically, the formulations of the invention can be used to treat Inflammatory Bowel Disease (IBD), and related conditions such as Irritable Bowel Syndrome (IBS), and other inflammatory disorders such as arthritis. The plants have been selected for their specific inhibition of the inflammatory mediators implicated in the pathogenesis of IBD, arthritis, and related conditions.... Inflammatory Bowel Disease is a heterogeneous group of diseases that have a common manifestation of (gut) mucosal inflammation. In general, IBD encompasses two major forms of intestinal inflammation: ulcerative colitis and Crohn's disease, known also as Crohn's ileitis, regional enteritis, or granulomatous colitis. Estimates place the domestic prevalence of these conditions between one and two million patients, with similar rates in other northern European countries [Crohn's & Colitis Foundation of America 1/99 Update]. The clinical and histopathologic features of IBD are well characterized; however the etiology and pathogenesis of IBD are still subjects of intense research. Currently, a variety of medical treatment modalities are used, with moderate success, to both control active "flare-ups" of IBD as well as to maintain remission(s). Aminosalicylate preparations such as sulfasalazine and mesalamine are the most common anti-inflammatory agents which are used to control ulcerative colitis and, to a lesser extent, Crohn's disease. While the specific mechanism remains undefined, inhibition of eicosanoid mediators such as prostaglandins and thromboxanes is the probable mechanism of action [Stein R B, Hanaur S B: Medical Therapy for Inflammatory Bowel Disease. GI Clin N Amer 1999;28(2):297-321]. Other typical treatments include corticosteroids and antibiotics such as metronidazole and ciprofloxacin for acute flares of disease. The other large category of drugs used in IBD is the immunomodulators, including azathioprine, methotrexate, and cyclosporine, the efficacy of which are principally related to their ability to inhibit T-cell related immune response and inflammatory cytokine cascades [Stotland B R, Lichtenstein M D: Newer

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Treatments for Inflammatory Bowel Disease. Primary Care 1996;23(3):577-608]. These treatments, unfortunately, induce worrisome side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment for inflammatory bowel disease with a fibronectin polypeptide Inventor(s): Burkly, Linda C. (West Newton, MA), Lobb, Roy R. (Westwood, MA) Correspondence: LOUIS MYERS; Fish & Richardson P.C. 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20030095969 Date filed: September 23, 2002 Abstract: A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of an antibody, polypeptide or other molecule recognizing VLA-4, a surface molecule expressed on most types of white blood cells and involved in leukocyte adhesion to endothelium and other tissus in the gut. Excerpt(s): This application is a continuation-in-part of Lobb U.S. Ser. No. 08/373,857, filed Jan. 18, 1995, which is a continuation-in-part of Lobb U.S. Ser. No. 08/284,603, filed Aug. 11, 1994, and of PCT/US93/00924 filed Feb. 2, 1993, which is the continuation-inpart of Lobb U.S. Ser. No. 07/835,139, filed Feb. 12, 1992, all of which are incorporated by reference.... The present invention relates to a treatment for inflammatory bowel disease (IBD). More particularly, this invention relates to the use of antibodies recognizing the integrin VLA-4 (very late antigen-4 ) in the treatment of EBD.... Inflammatory bowel disease, or IBD, is a collective term encompassing ulcerative colitis and Crohn's disease (ileitis), which are chronic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is confined to the large intestine (colon) and rectum, and involves only the inner lining of the intestinal wall. Crohn's disease may affect any section of the gastrointestinal tract (i.e., mouth, esophagus, stomach, small intestine, large intestine, rectum and anus) and may involve all layers of the intestinal wall. Both diseases are characterized by abdominal pain and cramping, diarrhea, rectal bleeding and fever. The symptoms of these diseases are usually progressive, and sufferers typically experience periods of remission followed by severe flareups. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of inflammatory bowel disease Inventor(s): Redmond, H. Paul; (Wilton, IE), Pfirrmann, Rolf W. (Lucerne, CH) Correspondence: ROTHWELL, FIGG, ERNST & MANBECK, P.C. 1425 K STREET, N.W. SUITE 800; WASHINGTON; DC; 20005; US Patent Application Number: 20030119824 Date filed: December 19, 2002 Abstract: Patients suffering from inflammatory bowel disease such as Crohn's disease or ulcerative colitis are treated either orally or intravenously with methylol transfer agents, such as taurolidine and/or taurultam. These agents can be used in combination with other drugs thereby allowing the use of smaller amounts of the other drugs and limiting unwanted side effects.

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Excerpt(s): The present application is a continuation of application Ser. No. 09/753,679, filed Jan. 4, 2001, which claims the benefit of U.S. Provisional Application No. 60/174,608, filed Jan. 5, 2000.... Inflammatory bowel disease (IBD) is of unknown etiology, although immunological mechanisms play a significant role. The two major disorders involved are ulcerative colitis and Crohn's disease. Both diseases are chronic relapsing disorders.... The exact pathogenesis of IBD is unknown. Various factors such as environmental, genetic, smoking and infectious agents have been suggested. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of inflammatory bowel disease by inhibiting binding and/or signalling through alpha4beta7 and its ligands and MAdCAM Inventor(s): Newman, Walter; (Boston, MA), Picarella, Dominic; (Boston, MA), Ringler, Douglas J. (Revere, MA) Correspondence: HAMILTON, BROOK, SMITH & REYNOLDS, P.C. 530 VIRGINIA ROAD; P.O. BOX 9133; CONCORD; MA; 01742-9133; US Patent Application Number: 20020172679 Date filed: April 8, 2002 Abstract: The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM. Excerpt(s): This application is a continuation of U.S. application Ser. No. 08/386,857, filed Feb. 10, 1995. The entire teachings of the above application are incorporated herein by reference.... Inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease, for example, can be a debilitating and progressive disease involving inflammation of the gastrointestinal tract affecting an estimated two million people in the United States. Symptoms include abdominal pain, cramping, diarrhea and rectal bleeding. IBD treatments have included anti-inflammatory drugs (such as, corticosteroids and sulfasalazine), immunosuppressive drugs (such as, 6mercaptopurine, cyclosporine and azathioprine) and surgery (such as, colectomy). Podolsky, The New England Journal of Medicine, 325:928-937 (1991) and Podolsky, The New England Journal of Medicine, 325:1008-1016 (1991).... Some studies have suggested that the cell adhesion molecule, ICAM-1, mediates leukocyte recruitment to inflammatory sites through adhesion to leukocyte surface ligands, i.e. Mac-1, LFA-1 or.alpha.4.beta.2 (Springer, Nature, 346:425-434 (1990)). In addition, vascular cell adhesion molecule-1 (VCAM-1), recognizing the.alpha.4.beta.1 integrin (VLA-4), has been reported to play a role in in vivo leukocyte recruitment as well (Silber et al., J. Clin. Invest. 93:1554-1563 (1994)). It has been proposed that IBD can be treated by blocking the interaction of ICAM-1 with LFA-1 or Mac-1 or VCAM-1 with.alpha.4.beta.1 (e.g., WO 93/15764). However, these therapeutic targets are likely involved in inflammatory processes in multiple organs, and a functional blockade would likely result in systemic immune dysfunction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of inflammatory bowel disease with IFN-gamma inhibitors Inventor(s): Ward, Rebecca H.R. (San Francisco, CA), Ashkenazi, Avi J. (San Mateo, CA) Correspondence: MERCHANT & GOULD PC; P.O. BOX 2903; MINNEAPOLIS; MN; 55402-0903; US Patent Application Number: 20030012790 Date filed: July 12, 2002 Abstract: The invention concerns a method for the prevention or treatment of inflammatory bowel disease by administering an interferon-.gamma. inhibitor. The invention further concerns pharmaceutical compositions and bispecific molecules useful in such method. Excerpt(s): The invention concerns the prevention or treatment of inflammatory bowel disease by administering an interferon-gamma (IFN-.gamma.) inhibitor.... Inflammatory bowel disease (IBD) is a collective term for ulcerative colitis (UC) and Crohn's disease, which are considered as two different entities, but have many common features and probably share at least some pathologic mechanisms. There is sufficient overlap in the diagnostic criteria for UC and CD that it is sometimes impossible to say which a given patient has; however, the type of lesion typically seen is different, as is the localization. UC mostly appears in the colon, proximal to the rectum, and the characteristic lesion is a superficial ulcer of the mucosa; CD can appear anywhere in the bowel, with occasional involvement of stomach, esophagus and duodenum, and the lesions are usually described as extensive linear fissures.... The aetiology of these diseases is unknown and the initial lesion has not been clearly defined; however, patchy necrosis of the surface epithelium, focal accumulations of leukocytes adjacent to glandular crypts, and an increased number of intraepithelial lymphocytes and certain macrophage subsets have been described as putative early changes, especially in Crohn's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of biologically active vitamin D compounds for the prevention and treatment of inflammatory bowel disease Inventor(s): Hayes, Colleen E. (Madison, WI), Nashold, Faye E. (Sun Prairie, WI) Correspondence: MEDLEN & CARROLL, LLP; Suite 350; 101 Howard Street; San Francisco; CA; 94105; US Patent Application Number: 20020128241 Date filed: December 21, 2001 Abstract: Methods of treating inflammatory bowel disease are described, and in particular the prevention and treatment of inflammatory bowel disease in humans as well as other animals. These methods involve the administration of biologically active vitamin D compounds, and therapeutic compositions thereof, so that the symptoms of Inflammatory Bowel Disease are reduced or relieved. Excerpt(s): The present invention relates to therapeutics for the prevention and treatment of inflammatory bowel disease, and in particular the prevention and treatment of inflammatory bowel disease in humans as well as other animals through the use of biologically active vitamin D compounds.... Inflammatory bowel diseases (IBD) are defined by chronic, relapsing intestinal inflammation of obscure origin. IBD refers to two distinct disorders, Crohn's disease and ulcerative colitis (UC). Both

Patents 291

diseases appear to involve either a dysregulated immune response to GI tract antigens, a mucosal barrier breach, and/or an adverse inflammatory reaction to a persistent intestinal infection. The GI tract luminal contents and bacteria constantly stimulate the mucosal immune system, and a delicate balance of proinflammatory and antiinflammatory cells and molecules maintains the integrity of the GI tract, without eliciting severe and damaging inflammation [MacDermott, R. P., J. Gastroenterology, 31:907:-916 (1996)]. It is unknown how the IBD inflammatory cascade begins, but constant GI antigen-dependent stimulation of the mucosal and systemic immune systems perpetuates the inflammatory cascade and drives lesion formation.... There is no known cure for IBD, which afflicts 2 million Americans. Current methods of managing IBD symptoms cost an estimated $1.2 billion annually in the United States alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of growth hormone secretagogues to treat systemic lupus erythematosus and inflammatory bowel disease Inventor(s): Pan, Lydia C. (Mystic, CT), Busch, Frank Robert; (Gales Ferry, CT), Lefker, Bruce A. (Gales Ferry, CT) Correspondence: Gregg C. Benson; Pfizer Inc. Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020013320 Date filed: June 14, 2001 Abstract: This invention is directed to methods for treating systemic lupus erythematosus and/or inflammatory bowel disease such as Crohn's disease or ulcerative colitis in a patient which comprise administering a growth hormone secretagogue (GHS), prodrug thereof or a pharmaceutically acceptable salt of said GHS or said prodrug. More particularly, the present invention provides such methods wherein the GHS is a compound of Formula I: 1or a prodrug thereof or a pharmaceutically acceptable salt of said GHS or said prodrug. This invention is also directed to combinations of a GHS and a second therapeutic agent, where said second therapeutic agent is known to be beneficial in the treatment of systemic lupus erythematosus and/or inflammatory bowel disease such as Crohn's disease or ulcerative colitis, to kits and pharmaceutical compositions comprising such a combination and to methods of treating systemic lupus erythematosus and/or inflammatory bowel disease such as Crohn's disease or ulcerative colitis using such combinations, pharmaceutical compositions and kits. Excerpt(s): This application claims priority from the provisional application U.S. Ser. No. 60/212,521, filed on Jun. 19, 2000, the benefit of which is hereby claimed under 37 C.F.R..sctn.1.78(a)(3).... The present invention provides methods of using growth hormone secretagogues, prodrugs thereof and pharmaceutically acceptable salts of said secretagogues and said prodrugs to treat systemic lupus erythematosus, Crohn's disease, inflammatory bowel disease (IBD) and ulcerative colitis. More specifically, the present invention provides such methods wherein the growth hormone secretagogues are certain compounds of Formula I below. This invention also provides combinations comprising a growth hormone secretagogue and a second therapeutic agent selected from methotrexate, dapsone, a glucocorticoid or an antimalarial. The invention also provides pharmaceutical compositions and kits comprising such combinations and methods of using such combinations, pharmaceutical compositions and kits in the

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treatment of systemic lupus erythematosus, Crohn's disease, IBD and ulcerative colitis.... The origin of autoantibody production in SLE is unclear but a role has been suggested for an antigen driven process, spontaneous B-cell hyper-responsiveness, or impaired immune regulation. Regardless of the etiology of autoantibody production, SLE is associated with the impaired clearance of circulating immune complexes secondary to decreased CR1 expression, defective Fc receptor function, or deficiencies of early complement components such as C4A. (Belmont, ibid.) It has been suggested that the apoptosis process is atypical in the lupus patient leading to the increased production of autoantibodies including antiphospholipid antibodies. (L. Casciola-Rosen et al., Proc. Natl. Acad. Sci. USA, 93, 1996, 1624-1629. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of sulodexide for the treatment of inflammatory bowel disease Inventor(s): Laster, Morris; (Jerusalem, IL), Shelach, Noa; (Jerusalem, IL), Spero, Michael; (Jerusalem, IL) Correspondence: PENNIE AND EDMONDS; 1155 AVENUE OF THE AMERICAS; NEW YORK; NY; 100362711 Patent Application Number: 20030008844 Date filed: May 16, 2002 Abstract: The present invention is directed to methods for preventing or treating inflammatory bowel disease by administering a composition comprising a therapeutically or prophylactically effective amount of a composition comprising between about 60% to 90% iduronylglycosaminoglycan sulfate and between about 10% to 40% dermatan sulfate, or a pharmaceutically acceptable salt, solvate, hydrate, or clathrate thereof. In a particular embodiment, a therapeutically or prophylactically effective amount of a composition comprising sulodexide, or a pharmaceutically acceptable salt, solvate, hydrate, or clathrate thereof is administered. The composition to be administered may also comprise one or more additional active ingredients selected from the group consisting of steroids, aminosalicylates, short-chain fatty acids, thioguanine derivatives, antibiotics, biological agents, antidepressants, and painrelievers. Excerpt(s): The present invention claims priority benefits of U.S. Provisional Application Serial No. 60/291,667 filed May 17, 2001, the disclosure of which is incorporated herein by reference in its entirety.... The present invention relates to methods of preventing and treating inflammatory bowel disease.... Inflammatory Bowel Disease (IBD) is a chronic recurrent inflammatory disease that affects either or both the small intestine and the colon. IBD comprises two major groups: Crohn's disease and ulcerative colitis. The disease affects the small intestine, colon, or both. IBD's cause(s) are not known, but a number of theories have been put forward. Genetic, infectious, immunologic, and even psychological factors have been implicated in a number of studies. For example, 15 to 30 percent of patients have at least one relative that also has IBD. Also, the immune system of patients with IBD have been shown to undergo many changes. Research are being done to determine if a specific gene or group of genes make a person more susceptible to the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with Crohn’s disease, 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 “Crohn’s disease” (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 Crohn’s disease. You can also use this procedure to view pending patent applications concerning Crohn’s disease. Simply go back to the following Web address: 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 CROHN’S DISEASE Overview This chapter provides bibliographic book references relating to Crohn’s disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Crohn’s disease 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 “Crohn’s disease” (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 Crohn’s disease: •

Coping with Crohn' Disease: Manage Your Physical Symptoms and Overcome the Emotional Challenges Source: Oakland, CA: New Harbinger Publications, Inc. 2001. 183 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: $15.95 plus shipping and handling. ISBN: 1572242655. Summary: Crohn's disease (CD) is a chronic gastrointestinal inflammatory disease that may affect any part of the digestive tract. The disease process can be somewhat mild, or it can be devastating. However, the diagnosis of a chronic medical condition can be overwhelming. This book offers a comprehensive discussion of the emotional and

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physical aspects of living with a chronic illness. The book provides basic medical information, but it is primarily designed to be used as a tool to aid the activities of daily life, as well as to promote a healthy lifestyle, despite the disease. Medical terminology has been kept to a minimum and a glossary of terms is provided in an appendix. Throughout the book, the author offers case illustrations based on real people who live with CD. Ten chapters cover a definition of Crohn’s disease and coping with the diagnosis; relationships with medical professionals; medical treatments for the condition; surgery and surgical options; coping with physical symptoms; emotional challenges; disclosing one's condition; the need for social support; and nutrition and CD. The book concludes with the glossary and a list of resource organizations, plus a list of references. 61 references.

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

Bailliere's International Practice and Research: Clinical Gastroenterology: Crohn's Disease (Bailliere's International Practice) by R.N. Allan, M.R.B. Keighly; ISBN: 0702024821; http://www.amazon.com/exec/obidos/ASIN/0702024821/icongroupinterna

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Controlling Crohn's Disease: The Natural Way by Virginia M. Harper, Tom Monte (Contributor) (2002); ISBN: 1575668319; http://www.amazon.com/exec/obidos/ASIN/1575668319/icongroupinterna

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Coping With Crohn's Disease and Ulcerative Colitis (Coping) by Christina Potter; ISBN: 0823939626; http://www.amazon.com/exec/obidos/ASIN/0823939626/icongroupinterna

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Coping with Crohn's Disease: Manage Your Physical Symptoms and Overcome the Emotional Challenges by Amy B. Trachter, Henry Wodnicki; ISBN: 1572242655; http://www.amazon.com/exec/obidos/ASIN/1572242655/icongroupinterna

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Crohn's disease by James Kyle; ISBN: 0433189002; http://www.amazon.com/exec/obidos/ASIN/0433189002/icongroupinterna

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Crohn's Disease by Cosimo Prantera (Editor), Burton I. Korelitz (Editor); ISBN: 0824794109; http://www.amazon.com/exec/obidos/ASIN/0824794109/icongroupinterna

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Crohn's Disease by Brooke (1985); ISBN: 0195199758; http://www.amazon.com/exec/obidos/ASIN/0195199758/icongroupinterna

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Crohn's Disease & Ulcerative Colitis by Fred Saibil, Fredric G. Saibil (1997); ISBN: 1552091147; http://www.amazon.com/exec/obidos/ASIN/1552091147/icongroupinterna

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Crohn's disease : aetiology, clinical manifestations and management; ISBN: 0333215605; http://www.amazon.com/exec/obidos/ASIN/0333215605/icongroupinterna

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Crohn's Disease and Ulcerative Colitis (Your Personal Health) by Fred Saibil (2003); ISBN: 1552977714; http://www.amazon.com/exec/obidos/ASIN/1552977714/icongroupinterna

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Crohn's Disease of the Gastrointestinal Tract (Clinical Gastroenterology Monographs Series.) by Howard. Schachter, et al; ISBN: 0471488968; http://www.amazon.com/exec/obidos/ASIN/0471488968/icongroupinterna

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Crohn's Disease: Treatment and Pathogenesis by Colm A. O'Morain; ISBN: 0849367360; http://www.amazon.com/exec/obidos/ASIN/0849367360/icongroupinterna

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Eating Right for a Bad Gut: The Complete Nutritional Guide to Ileitis, Colitis, Crohn's Disease and Inflammatory Bowel Disease by James Dr. Scala; ISBN: 0453007392; http://www.amazon.com/exec/obidos/ASIN/0453007392/icongroupinterna

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Everything You Need to Know About Crohn's Disease and Colitis (Need to Know Library) by Sandra Giddens, Owen Giddens; ISBN: 0823939960; http://www.amazon.com/exec/obidos/ASIN/0823939960/icongroupinterna

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Intestinal Inflammation (Colitis, Enteritis, Crohn's Disease): Treatment & Therapy Index of New Information by Amer Health Research Institue Staff (1997); ISBN: 0788316028; http://www.amazon.com/exec/obidos/ASIN/0788316028/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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Is Crohn's Disease a Mycobacterial Disease (Developments in Gastroenterology, Vol 14) by C. J. J. Mulder (Editor), Guido N.J. Tytgat (Editor) (1993); ISBN: 0792320263; http://www.amazon.com/exec/obidos/ASIN/0792320263/icongroupinterna

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LEE CROHN'S WORKSHOP A GLOBAL ASSESSMENT OF CROHN'S DISEASE by ECG LEE; ISBN: 0471258474; http://www.amazon.com/exec/obidos/ASIN/0471258474/icongroupinterna

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Living with Crohn's Disease by Joan Gomez (2000); ISBN: 0859698203; http://www.amazon.com/exec/obidos/ASIN/0859698203/icongroupinterna

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Management of Crohn's Disease by Emma Greig, David Rampton (2003); ISBN: 1841840866; http://www.amazon.com/exec/obidos/ASIN/1841840866/icongroupinterna

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Managing Your Child's Crohn's Disease and Ulcerative Colitis by Keith J. Benkov, Harland S. Winter; ISBN: 1571010238; http://www.amazon.com/exec/obidos/ASIN/1571010238/icongroupinterna

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Positive Options for Crohn's Disease: Self-Help and Treatment by Joan Gomez (2000); ISBN: 0897932781; http://www.amazon.com/exec/obidos/ASIN/0897932781/icongroupinterna

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Recent Advances in Crohn's Disease. Ed by A.S. Pena (Developments in Gastroenterology, 1) by A. S. Pena (Editor) (1981); ISBN: 9024724759; http://www.amazon.com/exec/obidos/ASIN/9024724759/icongroupinterna

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Straight from the Gut: Living With Crohn's Disease & Ulcerative Colitis (PatientCentered Guides) by Cliff Kalibjian (2003); ISBN: 059650005X; http://www.amazon.com/exec/obidos/ASIN/059650005X/icongroupinterna

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The Angry Gut: Coping With Colitis and Crohn's Disease by W. Grant Thompson (1993); ISBN: 0306444704; http://www.amazon.com/exec/obidos/ASIN/0306444704/icongroupinterna

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The Clinician's Guide to Ulcerative Colitis and Crohn's Disease by P. P. Jewell, et al; ISBN: 0443048037; http://www.amazon.com/exec/obidos/ASIN/0443048037/icongroupinterna

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The Complete Crohnie Handbook: A Comprehensive Guide for the Crohn's Disease Patient by Robert R. Pilkington; ISBN: 0971887101; http://www.amazon.com/exec/obidos/ASIN/0971887101/icongroupinterna

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The Crohn's Disease and Ulcerative Colitis Fact Book by Crohn's & Colitis Foundation (Editor), et al (1983); ISBN: 0684179679; http://www.amazon.com/exec/obidos/ASIN/0684179679/icongroupinterna

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The Daily Telegraph: Crohn's Disease and Ulcerative Colitis (The Daily Telegraph) by Fred Saibil; ISBN: 1841196711; http://www.amazon.com/exec/obidos/ASIN/1841196711/icongroupinterna

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The First Year---Crohn's Disease and Ulcerative Colitis: An Essential Guide for the Newly Diagnosed by Jill Sklar, Manuel Sklar; ISBN: 1569245320; http://www.amazon.com/exec/obidos/ASIN/1569245320/icongroupinterna

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The Good Gut Guide: Help for Ibs, Ulcerative Colitis, Crohn's Disease, Diverticulitis, Food Allergies, Other Gut Problems by Stephanie Zinser, R. John Nicholls (2003); ISBN: 0007138059; http://www.amazon.com/exec/obidos/ASIN/0007138059/icongroupinterna

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The management of Crohn's disease : proceedings of the Workshop on Crohn's Disease, Leyden, 23-25 October, 1975; ISBN: 0444152210; http://www.amazon.com/exec/obidos/ASIN/0444152210/icongroupinterna

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The New Eating Right for a Bad Gut : The Complete Nutritional Guide to Ileitis, Colitis, Crohn's Disease, and Inflammatory Bowel Disease by James Scala; ISBN: 0452279763; http://www.amazon.com/exec/obidos/ASIN/0452279763/icongroupinterna

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The Official Patient's Sourcebook on Crohn's Disease: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833869; http://www.amazon.com/exec/obidos/ASIN/0597833869/icongroupinterna

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The Surgical Management of Crohn's Disease & Ulcerative Joints by Devinder Kumar, John Alexander-Williams (1993); ISBN: 3540197303; http://www.amazon.com/exec/obidos/ASIN/3540197303/icongroupinterna

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Ulcerative colitis and Crohn's disease : and other diseases of the alimentary system in childhood; ISBN: 0806715111; http://www.amazon.com/exec/obidos/ASIN/0806715111/icongroupinterna

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Yet I Will Praise Him: Our Spiritual Odyssey of Living With Crohn's Disease by Bev Burk, Dorsey Burk (2000); ISBN: 1567224520; http://www.amazon.com/exec/obidos/ASIN/1567224520/icongroupinterna

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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 “Crohn’s disease” (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 •

Clinical and economic assessment: infliximab for the treatment of Crohn's disease. Author: Canadian Coordinating Office for Health Technology Assessment.; Year: 1996; Ottawa, Ont.: CCOHTA, [2002]

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Crohn's disease: clinical, immunological and genetic aspects Author: Meuwissen, Stephanus Gerard Maria.; Year: 1977; [Amsterdam?: s.n.], 1977

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Crohn's disease in Stockholm County, 1955-1974: a study of epidemiology, results of surgical treatment and long-term prognosis Author: Hellers, Göran.; Year: 1979; Stockholm: Distributed by the Almqvist; Wiksell Periodical Co., 1979

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Crohn's disease. Bryan N. Brooke, guest editor. Author: Brooke, Bryan N.; Year: 1972; London, Saunders [c1972]

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Crohn's workshop: a global assessment of Crohn's disease Author: Lee, Emanoel C. G.; Year: 1971; London: HM+M Publishers, c1981; ISBN: 0856020850

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Germ free animal studies on the aetiology of Crohn's disease Author: Bergstrand, Lars Olof.; Year: 1981; Stockholm: [s.n.], 1981

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Guidance on the use of infliximab for Crohn's disease Author: National Institute for Clinical Excellence (Great Britain).; Year: 1974; London: National Institute for Clinical Excellence, c200x; ISBN: 1842571672

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Idiopathic inflammatory bowel disease: Crohn's disease and chronic ulcerative colitis: the past, present, and future prospectives Author: Thomson, A. B. R. (Alan Bryan Robert),; Year: 1982; Ottawa, Ont., Canada: Canadian Public Health Association, 1982; ISBN: 0919245145

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Infliximab for the treatment of Crohn's disease: a systematic review and cost-utility analysis Author: Marshall, John K.,; Year: 2002; Ontario: Canadian Coordinating Office for Health Technology Assessment, [2002]; ISBN: 189462033X

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Is Crohn's disease a mycobacterial disease? Author: Mulder, C. J. J. (Chris J. J.); Year: 2002; Dordrecht; Boston: Kluwer Academic Publishers, c1992; ISBN: 0792320633

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Regional enteritis (Crohn's disease): symposium September 29-October 1, 1970 Author: Engel, Arthur,; Year: 1971; Stockholm, Nordiska bokhandelns förlag, 1971

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Studies on Crohn's disease: epidemiology, roentgenology of the colon, angiology, and angiography Author: Brahme, Folke.; Year: 1975; Malmö, [Sweden: s.n.], 1975

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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Terminale jejuno-ileitis bij het varken: in vergelijking met de ziekte van Crohn bij de mens = Terminal jejuno-ileitis in pigs: in comparison with Crohn's disease in man Author: Westendorp, Johannes Franciscus.; Year: 1965; Oss [Netherlands]: [s.n.], 1965?

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The effective management of Crohn's disease Author: Hawkey, C. J.; Year: 2002; London; San Francisco: Aesculapius Medical Press, 2001; ISBN: 1903044200

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

Treatment [for Ulcerative Colitis and Crohn's Disease] Source: in Zonderman, J. and Vender, R.S. Understanding Crohn Disease and Ulcerative Colitis. Jackson, MS: University Press of Mississippi. 2000. p. 56-76. Contact: Available from University Press of Mississippi. 3825 Ridgewood Road, Jackson, MS 39211-6492. (601) 432-6205. Fax (601) 432-6217. E-mail: [email protected]. PRICE: $28.00 plus shipping and handling. ISBN: 1578062039. Summary: Crohn's disease and ulcerative colitis, together known as inflammatory bowel disease (IBD), are chronic illnesses of unknown origin. This chapter on treatment of IBD is from a book that provides timely information about how to obtain and maintain the highest quality of life possible while living with IBD. The authors offer a patient's perspective on coping with IBD. The authors note that until the root causes of ulcerative colitis and Crohn disease are discovered and cures are found, these two maladies are best managed by an internist with some extra training in gastroenterology or by a gastroenterologist. For ulcerative colitis (UC), surgery (which is radical) is curative; once the diseased colon is removed, there is no more colitis. But the surgical removal of the colon is also life changing and is not a decision to be taken lightly. In the case of Crohn disease, surgery only corrects an immediate problem, such as obstruction, fistula, bleeding, abscess, severe perianal disease, or severe and persistent symptoms that do not respond to medical management. In Crohn disease, the disease tends to recur after surgery, sometimes quickly and sometimes many years later, usually above the place where the two portions of healthy bowel are sewn together. Drug therapy is used in IBD to reduce the symptoms of a flareup, and to induce and then maintain remission. The surgical options are illustrated with simple line drawings. 5 figures.

•

History of Crohn's Disease Source: in Chen, T.S., and Chen, P.S., eds. History of Gastroenterology: Essays on Its Development and Accomplishments. New York, NY: Parthenon Publishing Group, Inc. 1995. p. 195-199. Contact: Available from Parthenon Publishing. 1 Blue Hill Plaza, P.O. Box 1564, Pearl River, NY 10965. (800) 735-4744 or (914) 735-9363. Fax (914) 735-1385. PRICE: $88.00 (as of 1996). ISBN: 1850703655.

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Summary: This chapter on the history of Crohn's disease is from a compilation of essays that relate the emergence and history of the field of gastroenterology. The authors review the history of regional enteritis (Crohn's disease), trace the development of the condition, and discuss whether it is a new disease or merely one that is being diagnosed more frequently. Topics include early history, the work of Crohn, Ginzburg, and Oppenheimer, and the acceptance of granulomatous colitis as an entity distinct from ulcerative colitis. 5 figures. 39 references. •

Diagnosing Inflammatory Bowel Disease Source: in Zonderman, J. and Vender, R.S. Understanding Crohn Disease and Ulcerative Colitis. Jackson, MS: University Press of Mississippi. 2000. p. 3-22. Contact: Available from University Press of Mississippi. 3825 Ridgewood Road, Jackson, MS 39211-6492. (601) 432-6205. Fax (601) 432-6217. E-mail: [email protected]. PRICE: $28.00 plus shipping and handling. ISBN: 1578062039. Summary: Crohn's disease and ulcerative colitis, together known as inflammatory bowel disease (IBD), are chronic illnesses of unknown origin. This chapter on diagnosing IBD is from a book that provides timely information about how to obtain and maintain the highest quality of life possible while living with IBD. The authors offer a patient's perspective on coping with IBD. They caution that the diagnosis of IBD may be made quickly or may take a relatively long time, depending on the symptoms people have when they first visit a doctor because of distress. IBD is most commonly diagnosed in two age groups: young adulthood (ages 15 to 30 years), and middle age (ages 50 to 65 years). Prompt diagnosis and treatment of IBD is important; these are chronic, lifelong conditions that demand medical vigilance. In addition, those in their fifties are entering the age at which colorectal cancer becomes more prevalent; it is important that individuals be evaluated by a physician who can distinguish colitis from cancer. The chapter discusses the three classic symptoms that a doctor considers when assessing whether an individual has IBD: persistent or recurrent diarrhea (with or without rectal bleeding), pain, and fever. The authors review the laboratory tests and other diagnostic procedures that may be used, including sigmoidoscopy, colonoscopy, barium enema, and upper gastrointestinal (GI) x ray. The authors also describe the nine varieties (subtypes) of IBD: ulcerative proctitis, proctosigmoiditis, left sided colitis, pancolitis, gastroduodenal Crohn disease, jejunoileitis, ileitis, ileocolitis, and granulomatous colitis. 5 figures.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to Crohn’s disease 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

12 You will need to limit your search to “Directory” and “crohn’s disease” 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 “crohn’s disease” (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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NACC Directory 2000/01 Source: St. Albans, England: National Association for Colitis and Crohn's Disease (NACC). 2001. 13 p. Contact: Available from National Association for Colitis and Crohn's Disease (NACC). 4 Beaumont House, Sutton Road, St. Albans, Hertfordshire, AL1 5HH. 01727 844296. Email: [email protected]. Website: www.nacc.org.uk. PRICE: Single copy free to members. Summary: This booklet offers the Directory of the National Association for Colitis and Crohn’s disease (NACC), an organization based in England. The purpose of the directory is to provide information about NACC to its members. The directory covers NACC services, group details, involvement and fundraising, and membership. NACC services include support groups, NACC in Contact (a telephone network service), an information line, publications, a website (www.nacc.org.uk), a newsletter, the Welfare Fund, disability benefits, and a counseling project. Involvement and fundraising activities can include attending group meetings, becoming a committee member, offering to be a helper at events or activities, commenting on articles and sharing experiences in the newsletter, helping to raise funds for NACC research and other activities, and offering to share personal experiences with the media. The bulk of the directory lists group chairpeople and committee contacts, organized by location. The final section of the directory describes how to join NACC and the benefits of membership, then lists contact telephone numbers for other sources of help in England.

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CHAPTER 8. MULTIMEDIA ON CROHN’S DISEASE Overview In this chapter, we show you how to keep current on multimedia sources of information on Crohn’s disease. 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.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio 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 “Sound Recordings.” Type “Crohn’s disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on Crohn’s disease: •

Novel Therapies for Inflammatory Bowel Disease Source: Timonium, MD: Milner-Fenwick, Inc. 199x. (audiocassette). Contact: Available from Milner-Fenwick, Inc. 2125 Greenspring Drive, Timonium, MD 21093-9989. (800) 638-8652 or (301) 252-1700. PRICE: $14.95. Order number CAS 20. Summary: This audiocassette includes four programs about novel therapies for inflammatory bowel disease (IBD). Chaired by Dr. Richard P. MacDermott, the topics are: the use of Plauquenil (Dr. Lloyd F. Mayer, New York, NY); the use of methotrexate (Dr. Richard A. Kozarek, Seattle, WA); the use of cyclosporin (Dr. Simon Lichtiger, New York); and future directions in the therapy of IBD (Dr. Stephen B. Hanauer, Chicago, IL). (AA-M).

Bibliography: Multimedia on Crohn’s Disease 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

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multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in Crohn’s disease (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 Crohn’s disease (for more information, follow the hyperlink indicated): •

Anorectal Crohn's disease with extensive perineal sepsis [videorecording] Source: video produced by Audio-Visual Communications, the University of Chicago; Year: 1992; Format: Videorecording; [United States] F.M. Michelassi, L. Gottlieb, c1992

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Conservative surgical management of Crohn's disease [videorecording] Source: from the Film Library and Clinical Congress of ACS; University of Bologna, Clinica Chirugica II; Year: 1995; Format: Videorecording; Woodbury, Conn.: Ciné-Med, [1995]

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Crohn's disease [videorecording] Source: presented by the Department of Pediatrics, Emory University, School of Medicine; Year: 1987; Format: Videorecording; Atlanta, Ga: The University, c1987

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Crohn's disease [videorecording]. Year: 2002; Format: Videorecording; Carrollton, TX: HSTN, c2002

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Crohn's disease ileal-ileal, ileal-cecal, ileal-sigmoid fistulae [videorecording]: resections x 2 on-table colonic lavage primary anastomoses Source: from the Film Library and Clinical Congress of ACS; Year: 1995; Format: Videorecording; Woodbury, CT: CinéMed, [1995]

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Ileocolic resection for Crohn's disease [videorecording] Source: Videosurgery; Year: 1977; Format: Videorecording; Don Mills, Ont.: Southam Business Publications, c1977

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Inflammatory bowel disease [electronic resource] Source: Stefan Schreiber... [et. al.]; Year: 1999; Format: Electronic resource; Berlin: Springer, c1999

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Inflammatory bowel disease [videorecording] Source: a presentation of Films for the Humanities & Sciences; Information Television Network; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c2000

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Inflammatory bowel disease [videorecording]: diagnosis and management of Crohn's disease and ulcerative colitis Source: Daniel H. Present; Year: 1998; Format: Videorecording; Clifton, N.J.: Network for Continuing Medical Education, c1998

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Inflammatory bowel disease [videorecording]: medical, nutritional, and surgical management Source: presented by the American Dietetic Association, Division of Continuing Education, the American Medical Association, Division of Continuing Medical Studies, and t; Year: 1979; Format: Videorecording; Chicago, Ill.: American Medical Association, c1979

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Inflammatory bowel diseases [electronic resource] Source: the American Gastroenterological Association; Year: 2002; Format: Electronic resource; Timonium, MD: Distributed by Milner-Fenwick, c2002

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Laparoscopic ileocecectomy with intracorporeal anastomosis in Crohn's disease [videorecording] Source: from the Film Library and the Clinical Congress of ACS; Section of General Surgery, the University of Chicago; produced by Audio-Visual Communications, the; Year: 1993; Format: Videorecording; [Chicago, Ill.]: F. Michelassi: University of Chicago, c1993

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Laparoscopic management of complicated Crohn's disease [videorecording] Source: from the Film Library and the Clinical Congress of ACS, the Cleveland Clinic, Department of Colorectal Surgery, Minimally Invasive Surgery Center; Year: 2000; Format: Videorecording; [Woodbury, Conn.]: Ciné-Med, [2000]

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Laparoscopic-assisted ileocecectomy for Crohn's disease [videorecording] Source: from the Film Library and the Clinical Congress of ACS; a production of Mayo Clinic Video Communications and Audiovisual Services; Year: 1999; Format: Videorecording; [Woodbury, Conn.]: Ciné-Med, c1999

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Management dilemmas in inflammatory bowel disease [electronic resource]: interactive case studies with expert faculty Source: sponsored by Scienta Healthcare Education; Year: 1998; Format: Electronic resource; Washington, DC: Capital Education Corp. Bethesda, MD: Interactive Drama, c1998

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Medical & surgical management of Crohn's disease [videorecording]. Year: 2002; Format: Videorecording; Carrollton, TX: HSTN, c2002

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Operations for the complications of Crohn's disease [motion picture] Source: George E. Block; produced by Davis & Geck; Year: 1971; Format: Motion picture; Danbury, Conn.: Davis & Geck, [1971]

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Recurrent Crohn's disease [sound recording]: predictable patterns and clinical implications: recorded at DDW 1991 in New Orleans. Year: 1991; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, [1991]

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Stricturoplasty for Crohn's disease [videorecording] Source: author, Victor W. Fazio; produced by DG, Davis & Geck, Medical Device Division; Year: 1987; Format: Videorecording; [Wayne, N.J.]: American Cyanamid, c1987

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Surgical management of Crohn's disease; Distal pancreatectomy for chronic pancreatitis [videorecording] Source: Medicom International Incorporated; produced by Gregory Luque Productions, Inc; Year: 1987; Format: Videorecording; [Sarasota, Fla.]: Medicom, c1987

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Surgical treatment of anorectal complications in Crohn's disease [videorecording] Source: from the Film Library and the Clinical Congress of ACS; video produced by Audio-Visual Communications, the University of Chicago; Year: 1993; Format: Videorecording; [United States]: Fabrizio Michelassi, George Block, c1993

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Surgical treatment of small bowel Crohn's disease with multiple segments of involv[e]ment [videorecording] Source: produced by DG, Davis & Geck; Year: 1982; Format: videorecording; Danbury, Conn.: American Cyanamid, c1982

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The spectrum of disease and treatment of suppurative perianal Crohn's disease [videorecording] Source: American College of Surgeons; an educational service provided by DG, Davis+Geck; from the Division of Colon and Rectal Surgery, University of Minnesota; produc; Year: 1994; Format: Videorecording; [Wayne, N.J.]: American Cyanamid Co., c1994

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Ulcerative colitis & Crohn's disease [videorecording] Source: presented by the Warren Magnuson Clinical Center, National Institutes of Health, Office of Clinical Reports & Inquiries; a production of AVP Inc; Year: 1985; Format: Videorecording; [Los Angeles, Calif.]: Hospital Satellite Network, c1985

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CHAPTER 9. PERIODICALS AND NEWS ON CROHN’S DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Crohn’s disease.

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

Fracture risk increased in Crohn's disease patients who use corticosteroids Source: Reuters Medical News Date: September 10, 2003 http://www.reutershealth.com/archive/2003/09/10/professional/links/20030910epid 001.html

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Schering to start phase III trials of Leukine for Crohn's disease Source: Reuters Medical News Date: August 28, 2003

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M. avium implicated in Crohn's disease, perhaps also irritable bowel syndrome Source: Reuters Medical News Date: August 06, 2003

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British study links Crohn's disease to milk-borne bug Source: Reuters Health eLine Date: August 06, 2003

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Enzo says Crohn's disease drug effective in phase I Source: Reuters Industry Breifing Date: May 20, 2003

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Crohn's disease marker associated with spondyloarthropathies Source: Reuters Medical News Date: May 02, 2003

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FDA clears Remicade for expanded Crohn's disease indication Source: Reuters Medical News Date: April 03, 2003

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FDA clears JJ's Remicade for expanded Crohn's disease indication Source: Reuters Industry Breifing Date: April 03, 2003

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Refractory inflammatory bowel disease responds to pulse cyclophosphamide Source: Reuters Industry Breifing Date: March 03, 2003

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Triglycerides decrease effectiveness of elemental diet for Crohn's disease Source: Reuters Medical News Date: February 03, 2003

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Appendectomy linked to increased risk of Crohn's disease Source: Reuters Medical News Date: January 17, 2003

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Drug may treat multiple sclerosis, Crohn's disease Source: Reuters Health eLine Date: January 01, 2003

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Kidney can be target of pathology in Crohn's disease Source: Reuters Medical News Date: December 25, 2002

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Lactobacilli reduce inflammatory factors in Crohn's disease in vitro Source: Reuters Medical News Date: November 29, 2002

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High prevalence of osteoporotic vertebral fracture seen in Crohn's disease Source: Reuters Medical News Date: November 27, 2002

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Prior appendicectomy associated with less severe inflammatory bowel disease Source: Reuters Medical News Date: November 14, 2002

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Celltech arthritis drug works well in Crohn's disease study Source: Reuters Industry Breifing Date: October 17, 2002

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Fracture risk increased in patients with inflammatory bowel disease Source: Reuters Medical News Date: September 23, 2002

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Nonsmokers respond better to Crohn's disease drug Source: Reuters Health eLine Date: September 12, 2002

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Smoking reduces efficacy of infliximab for Crohn's disease Source: Reuters Industry Breifing Date: September 11, 2002

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No link found between Crohn's disease and increased fracture risk Source: Reuters Medical News Date: August 26, 2002

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Early-onset Crohn's disease per se does not seem to affect adult height Source: Reuters Medical News Date: August 06, 2002

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Cell Pathways begins pilot phase II study of Crohn's disease drug Source: Reuters Industry Breifing Date: July 22, 2002

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JJ's Remicade gets new Crohn's disease indication Source: Reuters Industry Breifing Date: July 01, 2002

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Isis launches second phase II trial for Crohn's disease drug Source: Reuters Industry Breifing Date: June 25, 2002

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Inflammatory bowel disease risk differentially affected by childhood factors Source: Reuters Medical News Date: June 14, 2002

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Crohn's disease drug shows long-term benefits Source: Reuters Health eLine Date: May 03, 2002

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Maintenance infliximab therapy can sustain clinical remission of Crohn's disease Source: Reuters Industry Breifing Date: May 02, 2002

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Maternal inflammatory bowel disease linked to adverse pregnancy outcomes Source: Reuters Medical News Date: April 23, 2002

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JJ's Remicade wins US priority review for new Crohn's disease indication Source: Reuters Industry Breifing Date: March 22, 2002

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Ivax plans to advance investigational Crohn's disease, post-menopausal symptom drugs Source: Reuters Industry Breifing Date: March 21, 2002

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Percutaneous drainage of Crohn's disease abscess often obviates surgery Source: Reuters Medical News Date: March 08, 2002

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Infliximab targets mucosal T cells that cause Crohn's disease Source: Reuters Industry Breifing Date: February 25, 2002

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Induction of interferon explains low efficacy of IL-10 therapy in Crohn's disease Source: Reuters Industry Breifing Date: February 04, 2002

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Elevated lipoprotein (a) may have role in thrombosis in Crohn's disease Source: Reuters Medical News Date: January 08, 2002

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Ultraviolet B radiation treats vitamin D deficiency due to Crohn's disease Source: Reuters Medical News Date: January 03, 2002

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Dietary triglyceride level of no import in Crohn's disease Source: Reuters Medical News Date: December 07, 2001

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Isis launches pivotal trial of Crohn's disease therapeutic Source: Reuters Industry Breifing Date: November 29, 2001

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Abnormal intestinal permeability seen in some spouses of Crohn's disease patients Source: Reuters Medical News Date: November 12, 2001

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Infliximab dosing should be individualized for Crohn's disease Source: Reuters Industry Breifing Date: October 23, 2001

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Potential new target identified for treatment of Crohn's disease Source: Reuters Medical News Date: October 22, 2001

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Birthday linked to Crohn's disease: Report Source: Reuters Health eLine Date: October 19, 2001

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Paediatric Crohn's disease risk may be linked to month of birth Source: Reuters Industry Breifing Date: October 18, 2001 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.

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

Newsletters on Crohn’s Disease Find newsletters on Crohn’s disease 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 “Crohn’s disease.” 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 “Crohn’s disease” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Role of Radiology in Evaluation of Inflammatory Bowel Disease Source: Pediatric Crohn's and Colitis Association Newsletter. p. 1, 3. May 1994.

Periodicals and News 313

Contact: Available from Pediatric Crohn's and Colitis Association, Inc. P.O. Box 188, Newton, MA 02168. (617) 244-6678. Summary: This newsletter article considers the role of radiology in the evaluation of inflammatory bowel disease (IBD). The author stresses that, while new diagnostic modalities are useful in many cases, the main tools for evaluation of IBD continue to be barium contrast studies of the gastrointestinal (GI) tract. The author explores the use of both the upper GI series and the barium enema. For each test, the author reviews the advantages and drawbacks and provides recommendations. The final section of the article summarizes the indications for newer modalities in evaluating IBD. Options reviewed include computerized tomography (CT scan), ultrasound, and nuclear medicine techniques. The author concludes that the pediatrician working together in consultation with the radiologist can decide the best test for the quickest and most accurate evaluation of IBD with the least morbidity.

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 “Crohn’s disease” (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 Crohn’s disease: •

Crohn's Disease and Ulcerative Colitis: Taming Painful Inflammatory Bowel Disease Source: Mayo Clinic Women's Healthsource. 4(6): 4-5. June 2000. Contact: Available from Mayo Foundation for Medical Education and Research. 200 First Street SW, Rochester, MN 55905. Summary: This health newsletter article describes inflammatory bowel disease (IBD), an umbrella term for Crohn's disease and ulcerative colitis (UC). The author notes that the cause of IBD is unclear, but abnormalities of the immune system are associated with these diseases. IBD is an inflammatory disease, and it is this inflammation that results in pain and diarrhea. Symptoms can also include weight loss, fatigue, rectal bleeding, and anemia. The location of the inflammation within the digestive tract is one of the features that differentiates Crohn's disease from ulcerative colitis. Crohn's disease can affect any part of the digestive tract, from the mouth to the anus, although inflammation is usually in the small intestine. With UC, inflammation is usually in the large intestine and rectum, and ulcers often form. These disorders may also cause other health complications, including an increased risk for developing colon cancer. The symptoms of Crohn's disease are similar to irritable bowel syndrome (IBS), so diagnostic tests to differentiate the diseases may include blood tests, flexible sigmoidoscopy, colonoscopy, and barium enema. Treatment of IBD depends on the severity of disease and the associated complications. Treatment strategies can include diet, medications, counseling, and surgery. While there is no cure for IBD, some people have long periods of remission when their symptoms are well controlled. One sidebar describes current research efforts on Crohn's disease and ulcerative colitis. 1 figure.

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•

Inflammatory Bowel Disease Source: Intestinal Fortitude. 10(3): 1-3. 2000. Contact: Available from Intestinal Disease Foundation. 1323 Forbes Avenue, Suite 200, Pittsburgh, PA 15219. (412) 261-5888. Summary: This article reviews the epidemiology and etiology of inflammatory bowel disease (IBD) which is generally divided into two main categories: ulcerative colitis (UC) and Crohn's disease (CD). UC involves inflammation of the mucosal lining of the rectum and colon (large intestine). The most common presenting symptom is bloody diarrhea with or without abdominal pain. CD, on the other hand, may involve all layers of the intestinal wall and can occur anywhere in the gastrointestinal tract. Bloody diarrhea can be a symptom of Crohn's disease, but more often the presenting symptoms are pain, fever, weight loss, nausea, vomiting, and general fatigue. Although there is clearly no one triggering factor identified as a cause of IBD, current research suggests there may be certain environmental, immunologic, or infective processes at hand. The author discusses smoking and UC, smoking and CD, diet, medications, genetic factors, immunology, and infectious factors. IBD occurs with a higher incidence in developed countries and generally manifests itself early in life (most cases occur between the ages of 10 to 40 years).

Academic Periodicals covering Crohn’s Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Crohn’s disease. In addition to these sources, you can search for articles covering Crohn’s disease 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 Crohn’s disease. 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 Crohn’s disease. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Crohn’s disease: Azathioprine •

Systemic - U.S. Brands: Imuran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202077.html

Corticosteroids •

Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html

•

Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Decadron Respihaler; Pulmicort Respules; Pulmicort Turbuhaler; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html

•

Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html

•

Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P. HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html

•

Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html

•

Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectosol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html

Cyclosporine •

Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202176.html

Infliximab •

Systemic - U.S. Brands: Remicade http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203667.html

Mercaptopurine •

Systemic - U.S. Brands: Purinethol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202350.html

Mesalamine •

Oral - U.S. Brands: Asacol; Pentasa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202734.html

•

Rectal - U.S. Brands: Canasa; Rowasa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202351.html

Researching Medications 317

Metronidazole •

Systemic - U.S. Brands: Flagyl; Protostat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202365.html

•

Vaginal - U.S. Brands: MetroGel-Vaginal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202704.html

Sulfasalazine •

Systemic - U.S. Brands: Azulfidine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202537.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. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to Crohn’s disease by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page

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(http://www.rarediseases.org/search/noddsearch.html), type “Crohn’s disease” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for Crohn’s disease: •

Florham Park, NJ 07932 http://www.rarediseases.org/nord/search/nodd_full?code=537

•

Chimeric A2 (human-murine) IgG monoclonal anti-TNF http://www.rarediseases.org/nord/search/nodd_full?code=629

•

CDP571 http://www.rarediseases.org/nord/search/nodd_full?code=860

•

TAK-603 http://www.rarediseases.org/nord/search/nodd_full?code=921

•

Infliximab (trade name: Remicade) http://www.rarediseases.org/nord/search/nodd_full?code=958

•

Thalidomide (trade name: Thalidomid) http://www.rarediseases.org/nord/search/nodd_full?code=982

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

321

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

13

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

322 Crohn’s Disease

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources 323

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Crohn’s disease” (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 19771 199 3 8 0 19981

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 “Crohn’s disease” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

16

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

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 20

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

Physician Resources 325

Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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/.

The Genome Project and Crohn’s Disease In the following section, we will discuss databases and references which relate to the Genome Project and Crohn’s disease. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual

21 Adapted 22

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 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. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “Crohn’s disease” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for Crohn’s disease: •

Inflammatory Bowel Disease 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?266600 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

Physician Resources 327

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “Crohn’s disease” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “Crohn’s disease” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

25

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 Crohn’s disease 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 Crohn’s disease. 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 Crohn’s disease. 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 “Crohn’s disease”:

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Other Guides Alzheimer's Disease http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html Ankylosing Spondylitis http://www.nlm.nih.gov/medlineplus/ankylosingspondylitis.html Autoimmune Diseases http://www.nlm.nih.gov/medlineplus/autoimmunediseasesgeneral.html Behcet's Syndrome http://www.nlm.nih.gov/medlineplus/behcetssyndrome.html Colonic Diseases http://www.nlm.nih.gov/medlineplus/colonicdiseasesgeneral.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/tutorials/crohnsdiseasloader.html Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseasesgeneral.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseasesgeneral.html Immune System and Disorders http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html Peptic Ulcer http://www.nlm.nih.gov/medlineplus/pepticulcer.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html Vasculitis http://www.nlm.nih.gov/medlineplus/vasculitis.html

Within the health topic page dedicated to Crohn’s disease, the following was listed: •

General/Overviews Crohn's Disease http://www.nlm.nih.gov/medlineplus/tutorials/crohnsdiseasloader.html Inflammatory Bowel Disease Source: American Gastroenterological Association http://www.gastro.org/public/brochures/ibd.html Introduction to Crohn's Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/aboutcd.html

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Diagnosis/Symptoms Abdominal Pain, Acute: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/527.html 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 Lower GI Series Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/lowergi/index.htm Upper GI Series Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/uppergi/index.htm

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Treatment Colostomy http://www.nlm.nih.gov/medlineplus/tutorials/colostomyloader.html Ileostomy, Colostomy and Ileoanal Reservoir Surgery Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/ileostomy/index.htm Laparoscopic Intestinal Surgery: A Guide for Patients Source: Cleveland Clinic Foundation http://www.clevelandclinic.org/health/healthinfo/docs/0900/0962.asp?index=4356 Surgery for Crohn's Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/surgerycd.html Treatment Options in IBD Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/treatmentoptions.html Types of Medications for Inflammatory Bowel Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/medications.html

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Nutrition Diet and Nutrition Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/diet.html

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Specific Conditions/Aspects Extraintestinal Complications of IBD: Arthritis Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/arthritis.html Extraintestinal Complications: Bone Loss Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/bone.html Extraintestinal Complications: Eye Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/eye.html Extraintestinal Complications: Kidney Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/kidney.html Extraintestinal Complications: Liver Disease Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/liver.html Extraintestinal Complications: Skin Disorders Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/skin.html Measles Vaccine and Inflammatory Bowel Disease (IBD) Source: National Immunization Program http://www.cdc.gov/nip/vacsafe/concerns/autism/ibd.htm Short Bowel Syndrome Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/shortbowel/index.htm

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Children Inflammatory Bowel Disease Source: Nemours Foundation http://kidshealth.org/parent/medical/digestive/ibd.html Treating IBD in Children and Adolescents Source: Crohn's & Colitis Foundation of America http://www.ccfa.org/medinfo/medinfo/kidsmeds.html

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From the National Institutes of Health Crohn's Disease Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/index.htm Crohn's Disease Source: National Institutes of Health http://www.nih.gov/news/WordonHealth/dec2001/story02.htm

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Latest News Steroids for Bowel Disease Up Fracture Risk Source: 09/10/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_13937 .html

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Organizations American Gastroenterological Association http://www.gastro.org/ Crohn's & Colitis Foundation of America http://www.ccfa.org/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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Pictures/Diagrams Atlas of the Body: The Digestive System Source: American Medical Association http://www.medem.com/MedLb/article_detaillb.cfm?article_ID=ZZZ7C4T46JC&s ub_cat=338

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Research Challenges in IBD Research: Updating the Scientific Agendas 2002 http://www.ccfa.org/medinfo/research/laychallenges.pdf

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Teenagers Inflammatory Bowel Disease Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/digestive/ibd.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Crohn’s disease. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive:

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Crohn's Disease. [Enfermedad de Crohn] Source: Camp Hill, PA: Chek-Med Systems, Inc. 1996. 2 p. Contact: Available from Chek-Med Systems, Inc. 200 Grandview Avenue, Camp Hill, PA 17011. (800) 451-5797. Fax (717) 761-0216. PRICE: $22 per pack of 50 pamphlets for order of 3-10 packs; 3 packet minimum. Discounts available for larger quantities and complete kits of gastroenterology pamphlets. Summary: This patient brochure, available in English and Spanish, provides information about Crohn's disease, a chronic, recurrent inflammatory disease of the intestinal tract, the cause of which is unknown. Information is included on potential causes, high risk groups, symptoms, diagnosis, disease course, complications, and treatment. Dietary and emotional factors associated with the management of this disease are discussed, as well as surgery. While there is no known cure for Crohn's disease, it can be managed with present treatments such as cortisone or steroids, antibiotics, and immune system suppressors. The importance of followup care as an essential part of treatment is stressed.

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 “Crohn’s disease” (or synonyms). The following was recently posted: •

ACR Appropriateness Criteriaâ„¢ for imaging recommendations for patients with Crohn's disease Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3255&nbr=2481&a mp;string=Crohn''s+AND+disease

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Management of Crohn's disease in adults Source: American College of Gastroenterology - Medical Specialty Society; 2001 March; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2802&nbr=2028&a mp;string=Crohn''s+AND+disease Healthfinder™

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

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Crohn's Disease Summary: Crohn's disease usually involves the small intestine, most often the lower part (the ileum). In some cases, both the small and large intestine (colon or bowel) are affected. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=735

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Crohn's Disease: New Drug May Help When Others Fail Summary: This FDA Consumer magazine article discusses the drug Remicade (infliximab), the first treatment licensed by the Food and Drug Administration specifically for Crohn's disease. Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4953 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Crohn’s disease. 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. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources

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

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

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

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

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

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

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

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

Associations and Crohn’s Disease The following is a list of associations that provide information on and resources relating to Crohn’s disease: •

American Celiac Society-Dietary Support Coalition Telephone: (973) 325-8837 Fax: (973) 669-8808 Email: [email protected] Background: The American Celiac Society-Dietary Support Coalition is a nonprofit selfhelp organization that provides support, education, and encouragement for people with Celiac Sprue and other dietary disorders and food allergies, including Dermatitis Herpetiformis, Crohn s Disease, Lactose Intolerance, and Wheat Intolerance. Through patient and general education, nationwide support groups, networking, referrals, and research, ACS/DCS works to increase the awareness of dietary disorders and to identify food products that may contain gluten-gliaden, lactose, corn or soya. ACS/DCS also publishes a newsletter, patient packets, brochures, and offers audio-visual aids for its members. The society offers some Spanish language materials, and has limited Spanish and Italian speaking resources. Relevant area(s) of interest: Crohn's Disease

•

Crohn's and Colitis Foundation of America Telephone: (212) 685-3440 Toll-free: (800) 932-2423 Fax: (212) 779-4098 Email: [email protected] Web Site: http://www.ccfa.org Background: The Crohn s and Colitis Foundation of America is a not-for-profit voluntary health organization dedicated to raising funds for research to determine the cause of and the cure for Crohn s Disease and colitis. Crohn s Disease and ulcerative colitis, collectively known as inflammatory bowel disease, are chronic digestive diseases of unknown cause. While Crohn s Disease may affect any part of the gastrointestinal tract and often results in swelling, soreness, and inflammation of layers of the large and/or small intestinal wall, Ul ulcerative colitis affects only the colon (large intestine), causing inflammation of the inner lining and resulting in diarrhea, often mixed with blood, cramping abdominal pain, and other symptoms. Established in 1967, the Crohn s and Colitis Foundation of America seeks to educate affected individuals, physicians, and the public about these disorders in order to increase awareness about the nature of these chronic disorders and help affected individuals confront their unique problems. In addition, the Foundation establishes support groups, engages in patient advocacy, plays an active role in government legislation, and provides medical referrals. Educational materials produced by the organization include a regular newsletter, reports, and informative brochures.

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Relevant area(s) of interest: Crohn's Disease •

Crohn's and Colitis Foundation of Canada Telephone: (416) 920-5035 Toll-free: (800) 387-1479 Fax: (416) 929-0364 Email: [email protected] Web Site: http://www.ccfc.ca Background: The Crohn s and Colitis Foundation of Canada (CCFC) is a not-for-profit voluntary health organization dedicated to raising funds for research to determine the cause of and the cure for Crohn s disease and colitis. Crohn s disease and ulcerative colitis, known as inflammatory bowel diseases, are chronic digestive disorders of unknown cause. Crohn s disease may affect any part of the digestive tract and often results in swelling, soreness, and inflammation of layers of the large and/or small intestinal wall. Ulcerative colitis affects the colon (large intestine), causing inflammation of the inner lining and resulting in diarrhea, often mixed with blood, cramping abdominal pain, and other symptoms. Established in 1974, CCFC s mission is to help find the cure for Crohn s disease and ulcerative colitis. The Foundation provides educational programs for affected individuals, their families, health professionals, and the general public. In addition, the Foundation provides educational and awareness initiatives through approximately 75 local CCFC volunteer groups and CCFC community education events, featuring leading IBD specialists. The Foundation publishes a brochure series in both French and English. Titles include 'Surgery and Inflammatory Bowel Disease,' 'Nutrition, Diet and Inflammatory Bowel Disease,' 'Medication for Inflammatory Bowel Disease,' 'Sexuality, Fertility, Pregnancy and Inflammatory Bowel Disease,' and 'Living with Inflammatory Bowel Disease.' 'The Journal,' a regularly published newsletter, is also available.

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Gastro-Intestinal Research Foundation Telephone: (312) 332-1350 Fax: (312) 332-4757 Background: The Gastro-Intestinal Research Foundation (GIRF) is a not-for-profit voluntary organization dedicated to raising funds to help promote ongoing gastroenterologic research. Gastroenterology is the study of the digestive system and the disorders that affect the digestive tract. Established in 1962 and consisting of 600 members, the Foundation has a registry and provides information to interested individuals. The Foundation also conducts two seminars on gastro-intestinal health issues each year. These seminars are free and open to the public. The Foundation has a variety of educational materials including a regular newsletter and produces brochures on inflammatory bowel disease and women s health issues relating to gastro-intestinal conditions.

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Hermansky-Pudlak Syndrome Network, Inc Telephone: (516) 922-3440 Toll-free: (800) 789-9477 Fax: (516) 922-4022 Email: [email protected] or [email protected] Web Site: http://www.medhelp.org/web/hpsn.htm

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Background: The Hermansky-Pudlak Syndrome (HPS) Network, a special interest group of the National Organization of Albinism and Hypopigmentation, is a voluntary not-for-profit support group for people and families affected by Hermansky-Pudlak syndrome. This is an inherited form of albinism that is characterized by lack of pigmentation in the skin, hair, and eyes; visual abnormalities; poor blood clotting due to platelet abnormalities; and abnormal storage of a wax-like material, called ceroid, in certain organs of the body. Established in 1992, the HPS Network is dedicated to networking individuals, families, and physicians for the purposes of education and research. The HPS Network is in frequent communication with researchers and communicates information concerning developments to its members. In addition, the Hermansky-Pudlak Syndrome Network provides a variety of educational and support materials through its database, reports, brochures, pamphlets, and regular newsletter. Please note that individuals who wish to communicate with the organization via fax should notify the Network before initiating transmission. •

Intestinal Disease Foundation Telephone: (412) 261-5888 Toll-free: (877) 587-9606 Fax: (412) 471-2722 Email: [email protected] Web Site: www.intestinalfoundation.org Background: The Intestinal Disease Foundation (IDF) is a nonprofit organization, located in pittsburgh, PA, whose mission is to improve the quality of life of adults and children affected by chronic digestive illness through information, guidance and support. These illnesses include inflammatory bowel disease (Crohn's disease and ulcerative colitis), short bowel syndrome, diverticular disease, gastroesophageal reflux disease (GERD), irritable bowel syndrome and other functional gastroiontestinal disorders. Services provided include a quarterly newsletter, 'Intestinal Fortitude', informational brochures, educational materials, and a volunteer phone network in which trained volunteers will talk on the phone with others sharing similar illnesses and experiences.

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National Association for Colitis and Crohn's Disease (UK) Telephone: 44(0) 1727 844296 Fax: 44(0) 1727 862550 Email: [email protected] Web Site: http://www.nacc.org.uk/ Background: The National Association for Colitis and Crohn's Disease (UK) is a national voluntary association in the United Kingdom dedicated to providing information and support services to people who are living with ulcerative colitis or Crohn's disease, which are both forms of inflammatory bowel disease (IBD). The Association is also committed to promoting and supporting research into the medical, health care, social, and psychological aspects of IBD. Ulcerative colitis is characterized by chronic inflammation and ulceration of the large intestine and the rectum. Affected individuals may experience associated pain; episodes of urgent, bloody diarrhea; fatigue; and other symptoms. Crohn's disease may affect any area of the gastrointestinal tract from the mouth to the rectum; however, in most cases, it is characterized by chronic inflammation, ulceration, and scarring of the wall of the small intestine. Associated

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symptoms and findings may include pain, fatigue, weight loss, episodes of urgent diarrhea, and other symptoms and findings. The National Association for Colitis and Crohn's Disease (UK) was established in 1979 and currently consists of over 27,000 members including affected individuals, their families and friends, health care professionals, and anyone who wishes to support the group's activities. The Association conducts regular meetings; offers local support through its area groups; has a network of trained volunteer counselors who provide telephone support; and offers information and support to families with children affected by IBD through its 'Smilie's People Network.' In addition, the Association has a fund for people in financial difficulty due to IBD and supports local hospitals through its area groups. The National Association for Colitis and Crohn's Disease (UK) also offers brochures, publishes a quarterly newsletter, and has a web site on the Internet. •

Pediatric Crohn's and Colitis Association, Inc Telephone: (617) 489-5854 Fax: (617) 489-5854 Email: [email protected] Web Site: http://pcca.hypermart.net Background: The Pediatric Crohn s and Colitis Association, Inc. (PCCA) is an international not-for-profit service organization dedicated to providing information and emotional support to families of children with inflammatory bowel disease (IBD) to help ensure that affected children reach their potential in today s society. Crohn s Disease and Ulcerative Colitis, collectively known as Inflammatory Bowel Disease, are chronic digestive diseases of unknown cause. While Crohn s Disease may affect any part of the gastrointestinal tract and often results in swelling, soreness, and inflammation of layers of the large and/or small intestinal wall, Ulcerative Colitis affects only the colon (large intestine), causing inflammation of the inner lining and resulting in diarrhea, often mixed with blood, cramping abdominal pain, and other symptoms. The Association was founded in 1988 by a group of parents with children affected by IBD to address the broad range of issues faced by the pediatric population with these disorders. Currently consisting of over 1,200 members, PCCA is dedicated to promoting pediatric research; providing educational, emotional, social, academic, and psychological support; and addressing the role of family dynamics in dealing with a chronic illness. The organization s services include a parent hotline; support groups; patient advocacy; networking services; and medical, educational, and psychological symposia. The organization also provides a variety of educational materials including brochures, pamphlets, an information packet, and a regular newsletter. Relevant area(s) of interest: Crohn's Disease, Ileitis, Inflammatory Bowel Disease, Regional Enteritis

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Reach Out for Youth with Ileitis and Colitis, Inc Telephone: (631) 293-3102 Fax: (631) 293-3103 Email: [email protected] Web Site: www.reachoutforyouth.org Background: Reach Out for Youth with Ileitis and Colitis, Inc. is a non-profit support organization dedicated to assisting families whose children have Inflammatory Bowel

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Disease (IBD) such as Ileitis or Colitis. Ulcerative Colitis is an inflammatory disease of the large intestine and is characterized by diarrhea, abdominal pain, fever, and bleeding from the rectum. Decreased appetite and weight loss may also occur. Ileitis or Crohn s Disease, also an inflammatory bowel disorder, can affect any portion of the digestive system and has symptoms that are similar to those of Colitis. Established in 1979 and consisting of approximately 400 members, the organization has helped hundreds of families cope with the effects of IBD. The group's goals include providing educational materials and emotional support to affected individuals and their families and organizing fundraising efforts to promote research into the causes and treatment of IBD. Educational seminars and a quarterly newsletter entitled 'Inner Circle' assist members by keeping them informed of current activities. A hotline offers interested individuals the opportunity to communicate on a one-to-one basis, especially when acute symptoms are present. Reach Out also continues to support the IBD clinical database established 13 years ago as a crucial research tool. Our educational brochure, 'The Inside Story' is available upon request. Relevant area(s) of interest: Crohn's Disease, Ileitis, Inflammatory Bowel Disease •

Spondylitis Association of America Telephone: (818) 981-1616 Toll-free: (800) 777-8189 Fax: (818) 981-9826 Email: [email protected] Web Site: http://www.spondylitis.org Background: The Spondylitis Association of America (SAA) is a national memberdirected, nonprofit organization dedicated to empowering persons living with ankylosing spondylitis (AS) through education, advocacy and support for patients, families and health professionals. Spondylitis is the most overlooked cause of persistent back pain in young adults and can affect over one million adults nationally. Established in 1983, the SAA takes a proactive, leadership role in promoting, funding and conducting research into the causes of AS. In 1988, in collaboration with NIAMS and ten major medical centers and universities in North America, the SAA co-founded the North American Spondylitis Consortium (NASC) to lead the North American fight in uncovering the genetic causes of spondylitis and related diseases. Among other educational activities, the SAA produces a bi-monthly newsletter and other publications.

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

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see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Crohn’s disease” (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 “Crohn’s disease”. 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 “Crohn’s disease” (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 “Crohn’s disease” (or a synonym) into the search box, and click “Submit Query.”

343

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.27

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

27

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

344 Crohn’s Disease

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)28: •

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/

28

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

Finding Medical Libraries 345

•

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/

346 Crohn’s Disease

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries 347

•

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/

348 Crohn’s Disease

•

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

349

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 Crohn’s disease: •

Basic Guidelines for Crohn’s Disease Amebiasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000298.htm Chlamydia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001345.htm Crohn's disease (regional enteritis) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000249.htm Ischemic colitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000258.htm LGV Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000634.htm Lymphoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001086.htm

350 Crohn’s Disease

•

Signs & Symptoms for Crohn’s Disease Abdominal fullness, gaseous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003124.htm Abdominal mass Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003274.htm Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Abdominal sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003137.htm Bowel sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003137.htm Clubbing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003282.htm Clubbing of the fingers or toes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003282.htm Constipation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003125.htm Delayed growth Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003021.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Erythema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Gastrointestinal bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003133.htm Gums, swollen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003066.htm Hematochezia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003130.htm Hyperactive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003256.htm

Online Glossaries 351

Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Joint pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Joint swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003262.htm Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Painful stools Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003131.htm Stools - foul smelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003132.htm Stools, bloody Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003130.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Tenesmus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003131.htm Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •

Diagnostics and Tests for Crohn’s Disease Albumin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003480.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Barium enema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003817.htm Colonoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003886.htm Endoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003338.htm

352 Crohn’s Disease

Fecal fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003588.htm HCT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003646.htm Hgb Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003645.htm Sedimentation rate 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 Small bowel biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003889.htm Stool culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003758.htm Stool guaiac Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003393.htm Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.htm Upper GI series Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003816.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Nutrition for Crohn’s Disease Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm Vitamin B12 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002403.htm Vitamins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002399.htm

•

Background Topics for Crohn’s Disease Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Endoscopic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002360.htm

Online Glossaries 353

Hyperbaric Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002375.htm Hyperbaric oxygen therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002375.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Vagina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002342.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

355

CROHN’S DISEASE 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 Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acute-Phase Proteins: Proteins that are secreted into the blood in increased or decreased quantities by hepatocytes in response to trauma, inflammation, or disease. These proteins can serve as inhibitors or mediators of the inflammatory processes. Certain acute-phase proteins have been used to diagnose and follow the course of diseases or as tumor markers.

356 Crohn’s Disease

[NIH]

Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] 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] Aetiology: Study of the causes of disease. [EU] 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] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albinism: General term for a number of inherited defects of amino acid metabolism in which there is a deficiency or absence of pigment in the eyes, skin, or hair. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of

Dictionary 357

osteoporosis. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits trypsin, neutrophil elastase, and other proteolytic enzymes. Commonly referred to as alpha 1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the PI (protease inhibitor) system. Hereditary A1PI deficiency is associated with pulmonary emphysema. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration.

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Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [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-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anal Fistula: A channel that develops between the anus and the skin. Most fistulas are the result of an abscess (infection) that spreads to the skin. [NIH] 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] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH]

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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] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioneurotic: Denoting a neuropathy affecting the vascular system; see angioedema. [EU] Angioneurotic Edema: Recurring attacks of transient edema suddenly appearing in areas of the skin or mucous membranes and occasionally of the viscera, often associated with dermatographism, urticaria, erythema, and purpura. [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] Anisakis: A genus of nematodes of the superfamily Ascaridoidea. Its organisms are found in the stomachs of marine animals and birds. Human infection occurs by ingestion of raw fish that contain larvae. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] 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] 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 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] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH]

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Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antispasmodics: Medicines that help reduce or stop muscle spasms in the intestines. Examples are dicyclomine (dy-SY-klo-meen) (Bentyl) and atropine (AH-tro-peen) (Donnatal). [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortitis: Inflammation of the wall of the aorta. [NIH] Apocrine Glands: Large, branched, specialized sweat glands that empty into the upper portion of a hair follicle instead of directly onto the skin. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA

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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] Appendicitis: Acute inflammation of the vermiform appendix. [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] Argipressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, cyclic 1-6 disulfide. The usual mammalian antidiuretic hormone, it is a cyclic nonapeptide with arginine in position 8 of the chain. Argipressin is used to treat diabetes insipidus and as hemostatic because of its vasoconstrictor action. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthralgia: Pain in the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Ascending Colon: The part of the colon on the right side of the abdomen. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] 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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to

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strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] 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] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Avian: A plasmodial infection in birds. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] 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

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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] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] 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] 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] Belladonna Alkaloids: Alkaloids obtained from various plants, especially the deadly nightshade (Atropa belladonna) variety acuminata; hyoscyamine and scopolamine atropine are classical, specific antimuscarinic agents with many pharmacologic actions; used mainly as antispasmodics. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzamides: Benzoic acid amides. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] 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] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH]

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Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] 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] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [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 Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and

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is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Bronchial: Pertaining to one or more bronchi. [EU] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Caecum: The blind pouch in which the large intestine begins and into which the ileum opens from one side. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the

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endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [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] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] 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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] 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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH]

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Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and 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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] 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] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [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] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangitis: Inflammation of a bile duct. [NIH]

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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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic 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] Cicatricial: Ectropion due to scar tissue on the margins or the surrounding surfaces of the eyelids. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which

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causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colectomy: An operation to remove the colon. An open colectomy is the removal of the colon through a surgical incision made in the wall of the abdomen. Laparoscopic-assisted colectomy uses a thin, lighted tube attached to a video camera. It allows the surgeon to remove the colon without a large incision. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collagenous Colitis: A type of colitis. Caused by an abnormal band of collagen, a threadlike protein. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] 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] 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

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and the hepatic duct. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative 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] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [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 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

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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] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constipation: Infrequent or difficult evacuation of feces. [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] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] 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] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Controlled study: group. [NIH]

An experiment or clinical trial that includes a comparison (control)

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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH]

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Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] 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] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystitis: Inflammation of the urinary bladder. [EU]

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Cystoid: Like a bladder or a cyst. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH]

Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [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]

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]

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Dermatitis: Any inflammation of the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Descending Colon: The part of the colon where stool is stored. Located on the left side of the abdomen. [NIH] Desmopressin: A synthetic analog of the natural hormone 8-arginine vasopressin (argipressin). Its action is mediated by the vasopressin receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating factor VIII and von Willebrand factor. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [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] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] 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] 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] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [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]

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Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] 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] 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] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] 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]

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Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] 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

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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] 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] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Enteric bacteria: Single-celled microorganisms that lack chlorophyll. Some bacteria are capable of causing human, animal, or plant diseases; others are essential in pollution control because they break down organic matter in the air and in the water. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] 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] Enteroscopy: An examination of the small intestine with an endoscope. The endoscope is inserted through the mouth and stomach into the small intestine. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a

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slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU]

Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Episiotomy: An incision of the posterior vaginal wall and a portion of the pudenda which enlarges the vaginal introitus to facilitate delivery and prevent lacerations. [NIH] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erysipelas: An acute infection of the skin caused by species of streptococcus. This disease most frequently affects infants, young children, and the elderly. Characteristics include pink-to-red lesions that spread rapidly and are warm to the touch. The commonest site of involvement is the face. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Infectiosum: Contagious infection with human B19 Parvovirus most commonly seen in school age children and characterized by fever, headache, and rashes of the face, trunk, and extremities. It is often confused with rubella. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known

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as a 'ghost' after hemolysis. [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 Perforation: A dilated vessel in the lower end of the esophagus that result from portal hypertension. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Exanthema: Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] 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] 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] Extracorporeal: Situated or occurring outside the body. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Familial polyposis: An inherited condition in which numerous polyps (tissue masses) develop on the inside walls of the colon and rectum. It increases the risk for colon cancer. [NIH]

Family Planning:

Programs or services designed to assist the family in controlling

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reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [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] 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] 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] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such

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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] 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] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [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 Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] 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] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [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

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between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [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 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] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Hemorrhage: Bleeding in the gastrointestinal tract. [NIH] Gastrointestinal stromal tumor: GIST. A type of tumor that usually begins in cells in the wall of the gastrointestinal tract. It can be benign or malignant. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] 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

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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] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] 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] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] 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] 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] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

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Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Goiter: Enlargement of the thyroid gland. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulomatous Colitis: Another name for Crohn's disease of the colon. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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]

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Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] 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] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis:

The process which spontaneously arrests the flow of blood from vessels

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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] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [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] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hidradenitis: The inflammation of a sweat gland (usually of the apocrine type). The condition can be idiopathic or occur as a result of or in association with another underlying condition. Neutrophilic eccrine hidradenitis is a relatively rare variant that has been reported in patients undergoing chemotherapy, usually for non-Hodgkin lymphomas or leukemic conditions. [NIH] Hidradenitis Suppurativa: A chronic suppurative and cicatricial disease of the apocrine glands occurring chiefly in the axillae in women and in the groin and anal regions in men. It is characterized by poral occlusion with secondary bacterial infection, evolving into abscesses which eventually rupture. As the disease becomes chronic, ulcers appear, sinus tracts enlarge, fistulas develop, and fibrosis and scarring become evident. Hormonal mechanisms are expected in its pathogenesis. [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] 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]

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Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [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] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH]

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Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypoxic: Having too little oxygen. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [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] Ileitis: Inflammation of the ileum. [EU] Ileocecal Valve: A valve that connects the lower part of the small intestine and the upper part of the large intestine (ileum and cecum). Controls the flow of fluid in the intestines and prevents backflow. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Ileus: Obstruction of the intestines. [EU] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: (antigens). [NIH]

The activity of the immune system against foreign substances

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances. [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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]

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Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]

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

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

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Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace

Dictionary 391

macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH]

Intestinal Obstruction: Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anus. [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] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intramuscular: IM. Within or into muscle. [NIH]

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Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intussusception: A rare disorder. A part of the intestines folds into another part of the intestines, causing blockage. Most common in infants. Can be treated with an operation. [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] Iodoacetamide: An alkylating sulfhydryl reagent. Its actions are similar to those of iodoacetate. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] 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] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacerations: Torn, ragged, mangled wounds. [NIH] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring

Dictionary 393

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] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH]

Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH] Library Services: circulation. [NIH]

Services offered to the library user. They include reference and

Lichen Nitidus: A chronic inflammatory disease characterized by shiny, flat-topped, usually flesh-colored micropapules no larger than the head of a pin. Lesions are localized in the early stages, found chiefly on the lower abdomen, penis, and inner surface of the thighs. Distribution may become generalized as the disease progresses. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or

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spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linoleic Acids: Eighteen-carbon essential fatty acids that contain two double bonds. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and 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 Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL

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increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] 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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphocyte Transformation: Morphologic alteration of small lymphocytes in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by interleukins, mitogens such as phytohemagglutinins, and by specific antigens. It may also occur in vivo, as in graft rejection and chronic myelogenous leukemia. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival,

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proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [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] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammogram: An x-ray of the breast. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [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]

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

Dictionary 397

substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: illnesses. [NIH]

Recording of pertinent information concerning patient's illness or

MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] 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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder:

A condition in which normal metabolic processes are disrupted,

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usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. [NIH] Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] Methylmethacrylate: The methyl ester of methacrylic acid. It polymerizes easily to form polymethyl methacrylate. It is used as a bone cement. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH]

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Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] 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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [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] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucosal Lining: The lining of GI tract organs that makes mucus. [NIH] Mucosal Ulceration: Skin ulceration in workers who work with lime and lime solutions. [NIH]

Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [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]

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Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [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] Mycobacterial disease: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myenteric: On stimulation of an intestinal segment, the segment above contracts and that below relaxes. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nafarelin: 6-(3-(2-Naphthalenyl)-D-alanine)luteinizing hormone-releasing factor (pig). A gonadorelin analog agonist. It has been used in the treatment of central precocious puberty and endometriosis. [NIH]

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Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [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] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [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] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel

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across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [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] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of

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nutrients. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] 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] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Opacity: Degree of density (area most dense taken for reading). [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornidazole: A nitroimidazole antiprotozoal agent used in ameba and trichomonas infections. It is partially plasma-bound and also has radiation-sensitizing action. [NIH] Orofacial: Of or relating to the mouth and face. [EU] 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] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [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] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the

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electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatectomy: Surgery to remove the pancreas. In a total pancreatectomy, a portion of the stomach, the duodenum, common bile duct, gallbladder, spleen, and nearby lymph nodes also are removed. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [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] 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] Paratuberculosis: An infectious disease caused by Mycobacterium paratuberculosis. Characteristics include chronic debilitation and weight loss. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH]

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Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pars Planitis: Form of granulomatous uveitis occurring in the region of the pars plana. This disorder is a common condition with no detectable focal pathology. It causes fibrovascular proliferation at the inferior ora serrata. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perianal: Located around the anus. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels.

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[NIH]

Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phorbol: Class of chemicals that promotes the development of tumors. [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]

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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] Photochemotherapy: Therapy using oral or topical photosensitizing agents with subsequent exposure to light. [NIH] Photopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (methoxsalen) and ultraviolet light - a procedure known as PUVA therapy. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases. [NIH] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Phytohemagglutinins: Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Piloerection: Involuntary erection or bristling of hairs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plant Diseases: Diseases of plants. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen:

Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of

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molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarthritis: An inflammation of several joints together. [EU] 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] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH]

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Polymethyl Methacrylate: Polymerized methyl methacrylate monomers which are used as sheets, moulding, extrusion powders, surface coating resins, emulsion polymers, fibers, inks, and films (From International Labor Organization, 1983). This material is also used in tooth implants, bone cements, and hard corneal contact lenses. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [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] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [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] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH]

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Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [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] Preoperative: Preceding an operation. [EU] Prepuce: A covering fold of skin; often used alone to designate the preputium penis. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Proctitis: Inflammation of the rectum. [EU] Proctocolectomy: An operation to remove the colon and rectum. Also called coloproctectomy. [NIH] Proctocolitis: Inflammation of the rectum and colon. [NIH] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH] Proctosigmoidoscopy: An examination of the rectum and the lower part of the colon using a thin, lighted tube called a sigmoidoscope. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] 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

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severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [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] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] 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] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] 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]

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Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] 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] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH]

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Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] 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] Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent. [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] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH]

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Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectovaginal Fistula: Abnormal communication between the rectum and the vagina. [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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional enteritis: Inflammation of the intestines, but usually only of the small intestine. Also called Crohn's disease. [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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative

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risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] 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] Reproduction Techniques: Methods pertaining to the generation of new individuals. [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] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticulata: Part of substantia nigra. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] 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] 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] 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] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH]

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Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Salicylic: A tuberculosis drug. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] 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] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [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] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of

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old age. [NIH] Senna: Preparations of Cassia senna L. and C. angustifolia of the Leguminosae. They contain sennosides, which are anthraquinone type cathartics and are used in many different preparations as laxatives. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Seton: A thin strand of linen or silk drawn through a cutaneus wound in order to lay down the foundations of a drain. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: female or male. [NIH]

The biological characteristics which distinguish human beings as

Sex Ratio: The number of males per 100 females. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] 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] Sigmoidoscope: A thin, lighted tube used to view the inside of the colon. [NIH] 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

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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] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [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, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Rectal Ulcer: A rare type of ulcer in the rectum. May develop because of straining to have a bowel movement. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH]

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Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [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,

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bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]

Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU]

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Sulfapyridine: Antibacterial, potentially toxic, used to treat certain skin diseases. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppository: A medicated mass adapted for introduction into the rectal, vaginal, or urethral orifice of the body, suppository bases are solid at room temperature but melt or dissolve at body temperature. Commonly used bases are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [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] 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] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Testicle: The male gonad where, in adult life, spermatozoa develop; the testis. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH]

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Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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]

Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone,

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which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH] Total pancreatectomy: Surgery to remove the entire pancreas. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Tributyrin: A triglyceride drug that may inhibit cell growth and induce cell differentiation.

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Differentiating agents may be effective in changing cancer cells back into normal cells. [NIH] Trichomonas: A genus of parasitic flagellate protozoans distinguished by the presence of four anterior flagella, an undulating membrane, and a trailing flagellum. [NIH] Trichomonas Infections: Infections in birds and mammals produced by various species of Trichomonas. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trivalent: Having a valence of three. [EU] Trophic: Of or pertaining to nutrition. [EU] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [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] Unsaturated Fats: A type of fat. [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

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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]

Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] 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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [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] 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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginal Fistula: An abnormal passage communicating with the vagina. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [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

426 Crohn’s Disease

body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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]

427

INDEX A Abdomen, 357, 364, 369, 374, 380, 392, 400, 402, 403, 404, 416, 417, 434, 435, 437, 442 Aberrant, 275, 286, 357 Ablation, 248, 357 Abortion, 357, 422 Abscess, 269, 272, 300, 310, 357, 361 Acceptor, 357, 403, 415 Acetylcholine, 357, 372, 413 Acetylglucosamine, 258, 357 Acidosis, 273, 357 Acute leukemia, 357, 423, 437 Acute lymphoblastic leukemia, 357 Acute lymphocytic leukemia, 357 Acute renal, 358, 393 Acute-Phase Proteins, 358 Adaptability, 358, 371 Adenocarcinoma, 358 Adipose Tissue, 358 Adolescence, 72, 358 Adrenal Cortex, 358, 377, 395, 423 Adrenal Glands, 358, 360 Adverse Effect, 6, 242, 358, 432 Aerobic, 358, 411 Aetiology, 270, 279, 284, 290, 297, 299, 358 Affinity, 280, 358, 406, 433 Age Groups, 301, 358 Age of Onset, 248, 358 Aged, 80 and Over, 358 Agonist, 358, 411, 413 Airway, 359 Alanine, 359, 411 Albinism, 340, 359 Alendronate, 359 Algorithms, 359, 368 Alkaline, 357, 359, 360, 366, 369 Alkaloid, 359, 365, 413, 430 Alleles, 359, 394 Allergen, 359, 431 Allergic Rhinitis, 359, 369 Allogeneic, 359, 392, 393 Alopecia, 359, 378 Alpha 1-Antitrypsin, 359 Alpha Particles, 359, 427 Alternative medicine, 312, 359 Aluminum, 265, 360 Amebiasis, 351, 360, 408 Ameliorating, 267, 272, 283, 360 Amine, 360, 394 Amino Acid Sequence, 360, 362, 390, 423

Amino-terminal, 360, 423 Ammonia, 360, 391, 436 Ampulla, 272, 360, 383 Amylase, 360 Amyloid, 360 Amyloidosis, 231, 360 Anaerobic, 269, 360, 411 Anaesthesia, 361, 398 Anal, 212, 361, 384, 388, 394, 404, 410 Anal Fistula, 361 Analgesic, 361, 396 Analog, 361, 380, 411 Anaphylatoxins, 361, 375 Anastomosis, 304, 361 Anatomical, 361, 368, 372, 397, 430 Androgens, 358, 361, 377 Anemia, 276, 277, 313, 327, 361, 388, 406 Anesthesia, 359, 361, 362 Angioedema, 361 Angiography, 300, 361 Angioneurotic, 361 Angioneurotic Edema, 361 Animal model, 265, 266, 271, 274, 282, 362 Anisakis, 362 Annealing, 362, 421 Anorectal, 304, 305, 362 Anorexia, 259, 263, 362, 389, 440 Anti-Anxiety Agents, 362, 423 Antibacterial, 362, 434, 436 Antibiotic, 241, 242, 362, 378, 423, 434, 435 Antibiotic Prophylaxis, 362, 423 Antibody therapy, 274, 362 Anticoagulant, 362, 425 Antidiuretic, 362, 364, 380 Antigen-Antibody Complex, 363, 375 Antigen-presenting cell, 363, 379 Anti-infective, 363, 395, 433 Anti-Inflammatory Agents, 287, 363, 377 Antimetabolite, 363, 408, 437 Antimicrobial, 270, 284, 363, 373, 380 Antimycotic, 363, 373 Antineoplastic, 363, 377, 378, 389, 408, 437 Antioxidant, 210, 217, 225, 268, 363, 364, 415 Antispasmodics, 363, 367 Antiviral, 363, 389, 399 Anus, 259, 276, 277, 288, 313, 361, 362, 363, 366, 369, 374, 383, 400, 418, 428 Anxiety, 244, 245, 362, 363 Aorta, 363, 408, 442 Aortitis, 363

428 Crohn’s Disease

Apocrine Glands, 363, 394 Apolipoproteins, 363, 404 Apoptosis, 292, 363, 370 Appendectomy, 308, 364 Appendicitis, 364 Aqueous, 364, 366, 378, 395 Arachidonic Acid, 364, 424 Arginine, 233, 264, 361, 364, 380, 413, 439 Argipressin, 364, 380 Arterial, 364, 372, 396, 425 Arteries, 363, 364, 368, 377, 404, 408, 409, 411, 438 Arteriolar, 364, 369 Arteritis, 364 Artery, 364, 368, 377, 416, 426, 442 Arthralgia, 364 Articular, 364, 415 Ascending Colon, 260, 364 Ascorbic Acid, 218, 228, 364, 395 Assay, 260, 262, 364 Asymptomatic, 226, 360, 364, 416 Ataxia, 327, 364, 437 Atmospheric Pressure, 365, 396 Atrophy, 269, 326, 327, 365 Atropine, 363, 365, 367, 430 Atypical, 270, 284, 292, 365 Autoantibodies, 292, 365 Autoantigens, 365 Autodigestion, 261, 365, 416 Autoimmune disease, 285, 365, 410, 419 Autoimmunity, 263, 273, 281, 365 Autologous, 248, 365, 393 Autologous bone marrow transplantation, 365, 393 Autonomic, 357, 365, 367, 418 Autonomic Nervous System, 365, 367, 418 Avian, 274, 365 B Back Pain, 342, 365 Bacteremia, 366 Bacterium, 270, 284, 285, 366, 376, 393 Barbiturate, 366, 437 Barium, 245, 275, 301, 313, 353, 366 Barium enema, 245, 275, 301, 313, 353, 366 Basal Ganglia, 365, 366 Basal Ganglia Diseases, 365, 366 Base, 248, 272, 366, 379, 387, 388, 390, 402, 440 Base Sequence, 366, 388, 390 Basement Membrane, 366, 386, 402 Basophils, 366, 392, 403 Belladonna, 265, 365, 367 Belladonna Alkaloids, 265, 367 Benign, 367, 390, 392, 412, 427

Benzamides, 257, 268, 367 Beta-pleated, 360, 367 Beta-Thromboglobulin, 367, 400 Bile, 282, 283, 367, 372, 389, 390, 395, 401, 404, 423, 434 Bile Acids, 367, 390, 434 Bile Acids and Salts, 367 Bile duct, 367, 372, 389, 423 Bile Pigments, 367, 401 Biliary, 220, 367, 370, 375, 416 Biliary Tract, 367, 370, 416 Bilirubin, 367, 389, 396 Bioavailability, 239, 367 Biochemical, 264, 359, 363, 367, 386, 402, 415 Biological response modifier, 368, 399 Biopsy, 73, 244, 245, 285, 354, 368 Biopsy specimen, 368 Biotechnology, 71, 299, 312, 323, 326, 327, 328, 368 Biotransformation, 368 Biphasic, 273, 368 Bismuth, 265, 368 Bladder, 368, 378, 410, 425, 441 Blood Coagulation, 368, 370, 438 Blood Glucose, 273, 368, 393, 399 Blood Platelets, 368, 437 Blood pressure, 368, 396, 409, 422, 433 Blood vessel, 361, 368, 372, 383, 391, 393, 401, 405, 408, 432, 433, 435, 437, 438, 441 Body Composition, 220, 368 Body Fluids, 368, 382, 433, 440 Body Regions, 368, 374 Bone Marrow, 357, 365, 368, 373, 378, 392, 393, 397, 405, 411, 423, 432, 435 Bowel Movement, 369, 380, 433, 435 Bradykinin, 264, 369, 401, 413 Branch, 349, 369, 405, 417, 426, 433, 437 Bronchial, 369, 394 Bronchoalveolar Lavage, 369 Buccal, 369, 404 Budesonide, 369 Bullous, 369 Butyric Acid, 269, 369 C Caecum, 259, 369 Calcification, 369 Calcium, 204, 369, 375, 409, 432 Calculi, 370, 391 Capillary, 369, 370 Capillary Permeability, 369, 370 Capsules, 240, 258, 273, 370, 381, 384, 390 Carbohydrate, 211, 219, 225, 273, 370, 377, 391, 421 Carcinogen, 370, 409

Index 429

Carcinogenic, 370, 398, 414, 424, 434 Carcinoma, 370 Cardiac, 370, 389, 411, 434 Carnitine, 370 Carotenoids, 370 Case report, 72, 217, 370 Caspase, 370 Catheter, 246, 370 Causal, 7, 270, 284, 370, 384, 393 Cecum, 370, 396, 402 Celiac Disease, 224, 370 Cell, 72, 74, 228, 240, 243, 244, 245, 248, 260, 265, 269, 278, 280, 287, 289, 292, 309, 326, 327, 358, 361, 363, 365, 366, 368, 370, 371, 372, 373, 375, 376, 377, 378, 379, 380, 382, 383, 386, 390, 392, 393, 395, 397, 398, 399, 400, 401, 402, 403, 405, 409, 410, 411, 412, 413, 414, 418, 419, 420, 424, 427, 429, 431, 432, 435, 436, 437, 438, 439, 440, 442 Cell Adhesion, 278, 289, 371, 399 Cell Death, 72, 363, 371, 390 Cell Differentiation, 371, 432, 439 Cell Division, 326, 366, 371, 409, 420, 431 Cell Lineage, 371 Cell membrane, 371, 373, 379, 419 Cell proliferation, 371, 400, 432 Cell Transplantation, 371, 393 Cellulose, 371, 420 Central Nervous System, 357, 359, 365, 371, 391, 393, 410, 430 Central Nervous System Infections, 371, 393 Centrifugation, 371, 409 Cerebellar, 365, 371, 428 Cerebral, 365, 366, 371, 372, 406, 433 Cerebral Cortex, 365, 371 Cerebral Palsy, 372, 433 Cerebrum, 371, 372, 440 Ceroid, 340, 372, 403 Character, 372, 379, 391 Cheilitis, 372 Chemotactic Factors, 372, 375 Chemotaxis, 222, 372 Chemotherapy, 221, 372, 394 Chin, 372, 407 Chlorophyll, 372, 383 Cholangitis, 7, 372 Cholelithiasis, 7, 372 Cholesterol, 367, 372, 373, 389, 404, 407, 434 Cholesterol Esters, 372, 404 Cholinergic, 372, 413 Chromatin, 364, 372, 384 Chromosomal, 286, 372, 373 Chromosome, 286, 373, 376, 392, 403, 431 Chronic myelogenous leukemia, 373, 405

Chronic renal, 373, 421, 440 Chylomicrons, 373, 404 Cicatricial, 373, 394 Ciprofloxacin, 287, 373 Cirrhosis, 7, 373, 422, 423 Citrus, 287, 364, 373 Clear cell carcinoma, 373, 379 Clinical Medicine, 226, 373, 422 Clinical trial, 7, 226, 239, 242, 247, 252, 323, 373, 377, 378, 381, 410, 425, 427 Cloning, 73, 368, 373 Clotrimazole, 242, 373 Coagulation, 368, 373, 393, 438 Coenzyme, 364, 374 Cofactor, 374, 425, 438 Cohort Studies, 374, 384 Colectomy, 242, 259, 278, 289, 374 Colic, 374 Collagen, 360, 366, 374, 387, 390, 395, 420, 423, 424 Collagen disease, 374, 395 Collagenous Colitis, 266, 270, 284, 374 Colonoscopy, 244, 245, 275, 301, 313, 333, 353, 374 Colorectal Cancer, 231, 260, 301, 374 Commensal, 267, 283, 374 Common Bile Duct, 375, 416 Complement, 292, 361, 375, 399, 406, 431 Complementary and alternative medicine, 217, 236, 375 Complementary medicine, 217, 375 Complete remission, 375, 428 Complete response, 375 Computational Biology, 323, 326, 375 Computed tomography, 376 Computerized tomography, 313, 376 Conception, 357, 376, 422, 434 Concomitant, 4, 376 Conjugation, 368, 376 Connective Tissue, 364, 369, 374, 376, 379, 387, 390, 405, 408, 429, 430, 436 Constipation, 285, 352, 376, 388, 418 Consultation, 245, 313, 376 Consumption, 204, 208, 212, 219, 376, 380, 389, 414, 429 Contamination, 376, 394 Contraception, 376, 403 Contraindications, ii, 376 Contrast medium, 361, 376 Controlled study, 240, 377 Conventional therapy, 4, 377 Conventional treatment, 377 Coordination, 377, 410 Coronary, 377, 409, 411

430 Crohn’s Disease

Coronary Thrombosis, 377, 409, 411 Corpuscle, 377, 385 Cortex, 233, 377, 428 Corticosteroid, 206, 243, 265, 377, 422 Cortisone, 336, 377, 422 Cranial, 377, 392, 401, 418 Craniocerebral Trauma, 366, 377, 393, 437 Cross-Sectional Studies, 377, 384 Crystallization, 378 Curative, 223, 263, 300, 378, 437 Cutaneous, 243, 378, 402, 404, 419 Cyanide, 378, 408 Cyclic, 212, 364, 378, 392, 413, 424 Cycloheximide, 264, 378 Cyclophosphamide, 248, 308, 378 Cyclosporine, 6, 278, 287, 289, 316, 378 Cyst, 378 Cystitis, 207, 378 Cystoid, 378 Cytokine, 225, 243, 260, 264, 280, 287, 378, 400, 437 Cytomegalovirus, 378 Cytoplasm, 364, 366, 371, 378, 384 Cytoskeleton, 378, 399 Cytotoxic, 264, 273, 281, 378, 397, 400, 427, 432 Cytotoxicity, 208, 210, 378 D Decarboxylation, 378, 394 Defense Mechanisms, 379, 399 Degenerative, 379, 394, 415, 429 Deletion, 364, 379 Demyelinating Diseases, 273, 379 Denaturation, 379, 421 Dendrites, 379, 413 Dendritic, 379, 407 Dendritic cell, 379 Density, 371, 379, 404, 414, 421, 433 Dental Caries, 379, 433 Depolarization, 379, 432 Dermatitis, 213, 226, 338, 379 Dermis, 361, 379 DES, 213, 361, 379 Descending Colon, 379 Desmopressin, 380 Detergents, 380, 387 Deuterium, 380, 395 Developed Countries, 277, 314, 380 Diagnostic procedure, 255, 301, 312, 380 Diarrhoea, 270, 273, 284, 380, 389 Diathesis, 380 Dietary Fats, 380, 403 Dietary Fiber, 226, 380

Digestion, 359, 367, 369, 380, 401, 403, 404, 417, 435 Digestive system, 204, 253, 339, 342, 380, 389 Digestive tract, 271, 277, 285, 295, 313, 339, 380, 432 Dihydrotestosterone, 380, 428 Dihydroxy, 274, 380 Dilatation, 357, 361, 380 Dilation, 267, 369, 380 Diploid, 381, 420 Direct, iii, 266, 275, 315, 373, 381, 390, 422, 428 Disease Progression, 7, 381 Disease Susceptibility, 381 Dissociation, 358, 381 Distal, 206, 269, 271, 305, 381, 390, 425 Diverticula, 381 Diverticulitis, 271, 298, 381 Diverticulum, 381 Dizziness, 276, 277, 381 Dominance, 281, 381, 385 Dosage Forms, 274, 278, 279, 381 Double-blind, 208, 240, 381 Drug Delivery Systems, 258, 381 Drug Interactions, 317, 381 Duct, 220, 360, 375, 382, 386, 430, 434 Duodenal Ulcer, 261, 382 Duodenum, 259, 261, 279, 290, 367, 382, 383, 389, 401, 416, 435 Dyes, 360, 366, 382 Dysplasia, 256, 257, 261, 327, 382 Dystrophic, 382, 385 Dystrophy, 327, 382 E Edema, 361, 382, 401, 412, 440 Effector, 3, 264, 357, 375, 382 Effector cell, 382 Efficacy, 4, 6, 207, 212, 228, 229, 240, 247, 248, 249, 250, 252, 287, 309, 310, 382 Elastic, 382, 391, 433 Electrocardiogram, 243, 244, 251, 382 Electrolyte, 226, 377, 382, 409, 433, 440 Embryo, 357, 371, 382, 398, 422, 434 Embryo Transfer, 382, 422 Emphysema, 359, 382 Encapsulated, 259, 382 Endemic, 382, 406, 434 Endogenous, 282, 283, 365, 382 Endometrial, 383 Endometriosis, 383, 403, 412, 414 Endometrium, 383 Endoscope, 244, 383, 384 Endoscopic, 7, 354, 374, 383, 432 Endoscopy, 220, 353, 383

Index 431

Endothelial cell, 383, 400, 438 Endothelium, 264, 276, 278, 288, 289, 383, 413, 420 Endothelium, Lymphatic, 383 Endothelium, Vascular, 383 Endothelium-derived, 383, 413 Endotoxin, 264, 280, 383, 440 End-stage renal, 373, 383, 421 Enema, 242, 247, 268, 274, 383 Enteral Nutrition, 204, 220, 221, 224, 228, 383 Enteric bacteria, 263, 383 Enteric-coated, 220, 258, 383 Enteritis, 271, 297, 341, 384 Enterocolitis, 72, 384 Enteroscopy, 384 Environmental Exposure, 384, 414 Environmental Health, 322, 324, 384 Enzymatic, 360, 370, 375, 379, 384, 394, 407, 421 Eosinophilia, 384, 386 Eosinophilic, 384, 386 Eosinophils, 267, 384, 392, 403 Epidemic, 384, 434 Epidemiologic Studies, 5, 384 Epidermal, 7, 261, 384, 402, 407 Epidermal Growth Factor, 7, 384 Epidermis, 379, 384, 402, 426 Epidermolysis Bullosa, 385 Epidural, 385 Episiotomy, 385 Epistasis, 73, 385 Epithelial, 221, 256, 257, 268, 358, 384, 385, 391, 394, 402, 416 Epithelial Cells, 256, 257, 268, 384, 385, 394, 402 Epithelium, 4, 256, 257, 267, 269, 271, 279, 290, 366, 383, 385, 389 Epitopes, 74, 385 Erection, 385, 419 Erysipelas, 385 Erythema, 352, 362, 385, 386, 441 Erythema Infectiosum, 385, 386 Erythrocyte Membrane, 227, 385 Erythrocytes, 361, 369, 385, 393, 419, 428, 431 Esophageal, 385 Esophageal Perforation, 385 Esophagus, 271, 276, 279, 285, 288, 290, 380, 385, 389, 390, 404, 419, 435 Essential Tremor, 327, 386 Ethanol, 386, 387 Ethnic Groups, 6, 386 Ethylmaleimide, 266, 386 Eukaryotic Cells, 386, 397, 415 Evacuation, 376, 386

Exanthema, 263, 386 Excipient, 273, 274, 386 Exhaustion, 386, 406 Exocrine, 386, 415 Exogenous, 368, 382, 386 Extensor, 386, 426 Extracellular, 360, 376, 386, 387, 399, 433 Extracellular Matrix, 376, 386, 387, 399 Extracorporeal, 243, 386, 419 F Faecal, 380, 386 Familial polyposis, 269, 386 Family Planning, 323, 386 Fasciitis, 386 Fatigue, 258, 313, 314, 341, 387 Fatty acids, 7, 208, 210, 224, 225, 269, 292, 387, 391, 403, 424, 433 Feces, 282, 283, 376, 386, 387, 435 Fermentation, 269, 387 Fertilization in Vitro, 387, 423 Fibrin, 368, 387, 418, 420, 437, 438 Fibrinogen, 387, 420, 437 Fibroblasts, 387, 400 Fibrosarcoma, 387 Fibrosis, 256, 257, 327, 387, 394, 430 Fish Oils, 204, 205, 387 Fistula, 207, 244, 285, 300, 387, 389 Fixation, 387, 431 Fluorescence, 388 Folate, 207, 215, 216, 388 Fold, 388, 408, 423 Folic Acid, 214, 215, 216, 388 Forearm, 368, 387, 388 Frameshift, 388 Frameshift Mutation, 388 Free Radicals, 363, 381, 388 Functional Disorders, 272, 388 G Gadolinium, 388 Gallbladder, 7, 357, 367, 380, 389, 416 Gallstones, 7, 367, 372, 389 Gamma Rays, 389, 427 Gamma-interferon, 208, 389, 399 Gas, 360, 388, 389, 395, 406, 413 Gasoline, 268, 389 Gastric, 261, 263, 365, 370, 381, 384, 389, 394, 414, 417 Gastric Juices, 389, 417 Gastric Mucosa, 389, 417 Gastrin, 389, 395 Gastritis, 231, 261, 389 Gastroduodenal, 301, 389 Gastroenteritis, 389 Gastroenterologist, 300, 389

432 Crohn’s Disease

Gastroesophageal Reflux, 340, 389 Gastrointestinal Hemorrhage, 390 Gastrointestinal stromal tumor, 390 Gastrostomy, 383, 390 Gelatin, 390, 391, 436 Gene Expression, 328, 390 Genetic Code, 390, 414 Genetic testing, 390, 421 Genetics, 376, 381, 390 Genital, 373, 390 Genotype, 390, 419 Giant Cells, 390, 430 Giardiasis, 390, 408 Gland, 358, 377, 390, 394, 405, 415, 416, 420, 425, 430, 435, 438 Glomerular, 391, 429 Glomerulus, 391, 412 Glucocorticoid, 291, 369, 391, 395, 422 Glucose, 264, 326, 364, 368, 371, 391, 393, 399, 430 Glutamic Acid, 388, 391, 413, 424 Glutamine, 7, 220, 221, 234, 391 Gluten, 338, 370, 391 Glycerol, 369, 391, 419 Glycerophospholipids, 391, 419 Glycine, 360, 367, 391, 413 Glycoprotein, 278, 359, 387, 390, 391, 402, 406, 410, 438, 440 Goblet Cells, 267, 391 Goiter, 391 Gonad, 391, 437 Gonadal, 391, 434 Gonadorelin, 391, 411 Gout, 260, 391 Governing Board, 392, 422 Graft, 392, 395, 405, 411 Graft Rejection, 392, 405 Graft-versus-host disease, 392, 411 Gram-negative, 273, 392, 411 Gram-positive, 392, 402, 411, 435 Granulocyte, 392, 400 Granuloma, 392 Granulomatous Colitis, 287, 301, 392 Groin, 392, 394 Guanylate Cyclase, 264, 392, 413 H Habitat, 392, 411 Haploid, 392, 420 Haplotypes, 392 Haptens, 358, 392 Headache, 263, 385, 392, 393 Headache Disorders, 393 Health Status, 246, 393

Hematopoietic Stem Cell Transplantation, 393 Heme, 367, 393, 415 Hemoglobin, 361, 385, 393, 402 Hemoglobinuria, 326, 393 Hemolysis, 385, 393 Hemolytic, 387, 393 Hemorrhage, 204, 205, 267, 377, 392, 393, 426, 435 Hemorrhoids, 285, 393 Hemostasis, 393, 399 Hepatic, 375, 393, 404 Hepatitis, 7, 394 Hepatitis A, 7, 394 Hepatocytes, 358, 394 Hepatovirus, 394 Hereditary, 359, 391, 394, 429 Heredity, 390, 394 Herpes, 394 Herpes virus, 394 Herpes Zoster, 394 Heterodimers, 394, 399 Heterogeneity, 358, 394 Heterozygotes, 381, 394 Hidradenitis, 394 Hidradenitis Suppurativa, 394 Histamine, 264, 361, 394, 395 Histidine, 394, 395 Homologous, 359, 394, 395, 431, 436 Hormonal, 365, 377, 394, 395 Hormone, 207, 246, 291, 364, 377, 379, 380, 389, 391, 395, 399, 403, 407, 411, 423, 429, 432, 437, 438 Hormone therapy, 395 Host, 5, 72, 237, 375, 395, 397, 441, 442 Humoral, 222, 281, 392, 395 Humour, 395 Hybrid, 395 Hybridoma, 260, 395 Hydrocortisone, 208, 395 Hydrogen, 357, 360, 366, 370, 379, 380, 395, 403, 409, 413, 415, 425 Hydrogen Peroxide, 395, 403 Hydrolysis, 368, 395, 419, 425, 439 Hydrophobic, 380, 391, 395, 404 Hydroxyproline, 360, 374, 395 Hyperbaric, 222, 224, 355, 396 Hyperbaric oxygen, 222, 224, 355, 396 Hyperbilirubinemia, 396, 401 Hypersensitivity, 359, 396, 429, 431 Hypertension, 396, 401, 422, 440 Hyperuricemia, 391, 396 Hypnotic, 366, 396, 437 Hypotensive, 273, 396, 402

Index 433

Hypoxic, 396, 408 I Ibuprofen, 396 Id, 214, 230, 336, 337, 348, 350, 396 Idiopathic, 258, 266, 271, 299, 394, 396, 426, 430 Ileitis, 242, 260, 266, 271, 276, 287, 288, 297, 298, 300, 301, 341, 342, 396 Ileocecal Valve, 259, 396 Ileostomy, 333, 396, 412 Ileus, 396 Imidazole, 373, 394, 396 Immune function, 396, 397 Immunity, 267, 281, 283, 359, 397, 400 Immunization, 334, 397, 431 Immunodeficiency, 326, 397 Immunoglobulin, 73, 262, 285, 362, 397, 410 Immunohistochemistry, 397 Immunologic, 3, 292, 314, 372, 397, 427 Immunosuppressant, 4, 263, 397, 408 Immunosuppressive, 4, 6, 241, 242, 245, 278, 289, 378, 391, 397, 436 Immunosuppressive Agents, 6, 397 Immunosuppressive therapy, 4, 397 Impairment, 364, 397, 400, 407 In situ, 397 In Situ Hybridization, 73, 397 In vitro, 205, 208, 211, 224, 309, 382, 397, 421, 436 In vivo, 224, 278, 281, 289, 397, 405, 436, 438 Incision, 374, 385, 398, 401 Incompetence, 390, 398 Indicative, 296, 398, 417, 441 Induction, 240, 280, 310, 361, 398, 400 Infant, Newborn, 358, 398 Infarction, 398 Infertility, 398 Infiltration, 260, 267, 272, 398 Infusion, 241, 246, 398 Ingestion, 362, 398, 420 Initiation, 398, 435 Initiator, 398, 400 Inlay, 398, 429 Inorganic, 398, 410, 433 Insight, 5, 398 Insulator, 399, 410 Insulin, 399, 401, 430 Insulin-dependent diabetes mellitus, 399 Insulin-like, 399 Integrins, 399 Intercellular Adhesion Molecule-1, 399 Interferon, 268, 279, 290, 310, 389, 399, 400, 405 Interferon-alpha, 399

Interleukin-1, 251, 260, 264, 281, 399, 400 Interleukin-10, 281, 399 Interleukin-12, 251, 400 Interleukin-18, 400 Interleukin-2, 211, 399, 400 Interleukin-4, 400 Interleukin-6, 260, 280, 400 Interleukin-8, 268, 400 Interleukins, 280, 397, 400, 405 Intermittent, 275, 400 Internal Medicine, 205, 206, 207, 208, 209, 210, 211, 213, 229, 266, 285, 389, 400 Interstitial, 207, 400, 412, 429 Intestinal Mucosa, 245, 370, 384, 400 Intestinal Obstruction, 400 Intracellular, 398, 399, 401, 407, 413, 424, 432 Intracranial Hypertension, 393, 401 Intraepithelial, 279, 290, 401 Intramuscular, 285, 401, 416 Intravenous, 208, 218, 241, 285, 398, 401, 416 Intrinsic, 269, 275, 286, 358, 366, 401 Intussusception, 401 Invasive, 72, 73, 276, 277, 304, 397, 401, 406 Involuntary, 366, 386, 401, 411, 419 Iodoacetamide, 266, 401 Ionizing, 359, 384, 401, 427 Ions, 366, 381, 382, 395, 401 Ischemia, 365, 401 Islet, 264, 401 Isozymes, 401 J Jaundice, 7, 396, 401 Jejunostomy, 383, 401 Jejunum, 259, 401 Joint, 246, 258, 353, 364, 373, 401, 415, 436 K Kallidin, 369, 401 Kb, 322, 402 Keratinocytes, 400, 402 Kidney Disease, 240, 247, 253, 322, 327, 335, 337, 402 L Labile, 375, 402 Lacerations, 385, 402 Lactobacillus, 213, 223, 224, 229, 402 Laminin, 366, 402 Laparoscopy, 402 Latent, 260, 402 Lavage, 304, 402 Lectin, 210, 402, 407 Leishmaniasis, 281, 402 Leprosy, 281, 402 Leucine, 229, 402, 417 Leucocyte, 204, 403, 405

434 Crohn’s Disease

Leukapheresis, 243, 244, 245, 403 Leukemia, 222, 326, 373, 403, 423 Leukocytes, 243, 278, 279, 289, 290, 366, 369, 372, 384, 399, 400, 403, 440 Leukopenia, 263, 276, 277, 403 Levonorgestrel, 403, 414 Library Services, 348, 403 Lichen Nitidus, 403 Life cycle, 368, 403 Ligament, 403, 425 Ligands, 277, 278, 289, 399, 403 Linkage, 403 Linoleic Acids, 7, 403 Lipase, 235, 403 Lipid, 363, 370, 372, 391, 399, 403, 404, 410, 415, 439 Lipid Peroxidation, 403, 415 Lipofuscin, 372, 403 Lipopolysaccharide, 273, 392, 403 Lipoprotein, 311, 392, 404 Liver Cirrhosis, 230, 404 Liver Transplantation, 7, 404 Localization, 279, 290, 397, 404 Localized, 265, 360, 361, 379, 382, 388, 398, 402, 403, 404, 420, 430, 440, 441 Locomotion, 404, 420 Longitudinal study, 404 Low-density lipoprotein, 404 Lower Esophageal Sphincter, 390, 404 Lubricants, 404, 418 Lumbar, 365, 404 Lumen, 259, 261, 383, 404 Lupus, 260, 291, 292, 404, 436 Lymph, 377, 383, 395, 404, 405, 416, 430, 435 Lymph node, 405, 416, 430 Lymphatic, 383, 398, 404, 405, 408, 434, 438 Lymphatic system, 405, 434, 438 Lymphoblastic, 405 Lymphoblasts, 357, 405 Lymphocyte, 211, 274, 363, 405, 406, 407 Lymphocyte Subsets, 274, 405 Lymphocyte Transformation, 211, 405 Lymphoid, 362, 403, 405 Lymphoma, 5, 221, 222, 243, 326, 351, 405, 419 Lymphoproliferative, 405 Lysine, 405, 423, 439 Lytic, 405, 431 M Macrophage, 279, 290, 399, 405 Macrophage Colony-Stimulating Factor, 405 Magnetic Resonance Imaging, 206, 406 Maintenance therapy, 244, 406

Major Histocompatibility Complex, 392, 400, 406 Malabsorption, 232, 326, 370, 406, 432 Malabsorption syndrome, 406, 432 Malaria, 406 Malaria, Falciparum, 406 Malaria, Vivax, 406 Malignancy, 269, 406 Malignant, 326, 358, 363, 387, 390, 406, 412, 427, 430 Malnutrition, 6, 365, 406, 410 Mammogram, 369, 406, 409 Measles Virus, 406 Meat, 270, 284, 380, 407 Mediate, 264, 280, 407 Mediator, 400, 407 Medical Records, 243, 244, 251, 407, 429 MEDLINE, 323, 326, 327, 407 Melanocytes, 407 Melanoma, 326, 407 Membrane Lipids, 407, 419 Membrane Proteins, 407, 425 Memory, 362, 407 Mental, iv, 253, 322, 324, 328, 372, 381, 387, 398, 407, 426, 440, 441 Mental Disorders, 253, 407 Mental Health, iv, 253, 322, 324, 407, 426 Mercaptopurine, 4, 6, 207, 221, 278, 289, 316, 408 Mesenchymal, 384, 405, 408 Mesenteric, 408, 422 Mesenteric Arteries, 408 Mesentery, 408, 418, 434 Meta-Analysis, 408 Metabolic disorder, 391, 408 Metabolite, 263, 368, 408, 419, 423 Metastasis, 408 Metastatic, 408 Methotrexate, 4, 239, 246, 287, 291, 303, 408 Methoxsalen, 408, 419 Methylene Blue, 408 Methylmethacrylate, 278, 408 Methyltransferase, 408 Metronidazole, 6, 238, 263, 287, 317, 408 MI, 283, 355, 409 Microbe, 409, 438 Microbiology, 365, 409 Microcalcifications, 369, 409 Microcirculation, 404, 409, 420 Microorganism, 374, 409, 417, 442 Microscopy, 366, 409 Microsomal, 409 Migration, 399, 409 Mineralocorticoids, 358, 377, 409

Index 435

Mitosis, 364, 409 Modification, 224, 360, 409, 426 Monitor, 282, 283, 409, 414 Monoclonal, 73, 250, 251, 252, 259, 260, 318, 410, 427, 430 Monocyte, 406, 410 Mononuclear, 230, 387, 392, 405, 410, 440 Morbillivirus, 406, 410 Motility, 285, 388, 410 Motion Sickness, 410, 412, 430 Mucins, 391, 410 Mucocutaneous, 402, 410 Mucolytic, 369, 410 Mucosa, 73, 256, 257, 269, 272, 279, 285, 290, 389, 404, 410 Mucosal Lining, 314, 410 Mucosal Ulceration, 260, 410 Mucus, 271, 272, 282, 283, 410, 440 Multicenter study, 410 Multiple sclerosis, 273, 308, 410 Multivariate Analysis, 410 Muscle Fibers, 410 Muscular Atrophy, 327, 410 Muscular Dystrophies, 382, 411 Mutagens, 388, 411 Mycobacterial disease, 299, 411 Mycophenolate mofetil, 207, 411 Mycoplasma, 371, 411 Mydriatic, 380, 411, 430 Myelin, 379, 410, 411 Myelodysplastic syndrome, 205, 411, 432 Myeloma, 395, 411 Myelosuppression, 411 Myenteric, 411 Myocardial infarction, 367, 377, 409, 411 Myocarditis, 411 Myocardium, 409, 411 Myotonic Dystrophy, 327, 411 N Nafarelin, 411 Nasogastric, 383, 412 Natural killer cells, 400, 412 Nausea, 263, 276, 277, 314, 381, 389, 412, 426, 440 NCI, 1, 252, 321, 412 Necrotizing Enterocolitis, 412 Neoplasia, 326, 412 Neoplasm, 412, 430, 440 Neoplastic, 260, 395, 405, 412 Nephritis, 412 Nephropathy, 402, 412 Nephrosis, 412 Nephrotic, 412 Nephrotic Syndrome, 412

Nerve, 361, 365, 372, 377, 379, 388, 407, 410, 412, 416, 422, 426, 429, 430, 435 Nervous System, 327, 365, 371, 407, 412, 413, 418, 436 Neural, 264, 360, 395, 412 Neurons, 379, 413, 436 Neuropathy, 361, 413 Neurotoxicity, 413 Neurotransmitter, 357, 360, 369, 391, 395, 413, 432, 435, 436 Neutrons, 359, 413, 427 Neutrophil, 222, 256, 257, 262, 275, 286, 359, 399, 413 Neutrophil Infiltration, 256, 257, 413 Nicotine, 258, 413 Nitric Oxide, 263, 264, 413 Nitrogen, 359, 360, 361, 378, 388, 391, 413 Nonverbal Communication, 413, 426 Norgestrel, 403, 413 Nuclear, 212, 313, 366, 376, 386, 389, 414, 440 Nuclear Medicine, 212, 313, 414 Nuclei, 359, 376, 406, 409, 413, 414, 425 Nucleic acid, 267, 283, 366, 390, 397, 411, 413, 414 Nucleus, 364, 365, 366, 372, 378, 380, 384, 386, 389, 410, 413, 414, 425, 435, 437 Nutritional Status, 6, 414 O Occult, 414 Odds Ratio, 414, 428 Ointments, 381, 414, 433 Omeprazole, 261, 414, 425 Oncogene, 326, 414 Oncogenic, 399, 414 Opacity, 379, 414 Opportunistic Infections, 273, 414 Organ Transplantation, 6, 415 Organelles, 371, 378, 407, 415 Ornidazole, 415 Orofacial, 204, 212, 415 Osteoarthritis, 415 Osteonecrosis, 415 Osteoporosis, 359, 415 Oxidation, 264, 269, 357, 363, 368, 403, 415 Oxidation-Reduction, 368, 415 Oxidative Stress, 217, 238, 415 Oxygenase, 415 Oxygenation, 415 P Paediatric, 209, 212, 213, 229, 258, 311, 415 Palliative, 415, 437 Pancreas, 357, 380, 389, 399, 401, 403, 415, 416, 434, 438, 439, 440 Pancreatectomy, 305, 416

436 Crohn’s Disease

Pancreatic, 232, 264, 326, 370, 390, 416 Pancreatic cancer, 326, 416 Pancreatic Juice, 390, 416 Pancreatitis, 230, 305, 416 Paneth Cells, 416 Paralysis, 416, 433 Parasite, 416, 439 Parasitic, 271, 416, 439 Paratuberculosis, 73, 74, 226, 270, 284, 416 Parenteral, 7, 220, 221, 224, 227, 228, 285, 416 Parenteral Nutrition, 7, 227, 416 Parietal, 414, 416, 418 Parotid, 416, 430 Paroxysmal, 326, 393, 417 Pars Planitis, 417 Partial remission, 417, 428 Pathogen, 237, 417 Pathogenesis, 5, 265, 266, 267, 275, 282, 283, 286, 287, 289, 297, 394, 417 Pathologic, 265, 279, 290, 357, 364, 368, 377, 396, 417, 422, 426 Pathologic Processes, 364, 417 Pathophysiology, 72, 207, 210, 266, 417 Patient Advocacy, 338, 341, 417 Patient Education, 335, 346, 348, 355, 417 Pelvic, 383, 417, 425 Pelvis, 357, 404, 417 Penis, 403, 417, 423 Pepsin, 417 Pepsin A, 417 Peptic, 261, 332, 417 Peptic Ulcer, 261, 332, 417 Peptide, 224, 272, 273, 280, 360, 417, 423, 425 Perforation, 265, 267, 418 Perianal, 222, 224, 259, 300, 305, 418 Pericarditis, 418 Pericardium, 418, 436 Perineal, 222, 304, 418 Perineum, 418 Perioperative, 210, 418 Peripheral blood, 248, 393, 399, 418, 419, 423 Peripheral Nervous System, 379, 413, 418, 435 Peritoneum, 408, 418 Peritonitis, 232, 265, 418 Peroxide, 418 Petroleum, 268, 389, 418 Phagocyte, 405, 418 Pharmaceutical Solutions, 381, 418 Pharmacokinetic, 238, 239, 418 Pharmacologic, 361, 367, 418, 438 Pharynx, 390, 418 Phenotype, 419 Phenyl, 277, 419

Phorbol, 210, 419 Phospholipases, 419, 432 Phospholipids, 387, 404, 407, 419 Phosphorus, 369, 419 Photochemotherapy, 419 Photopheresis, 243, 419 Photosensitizing Agents, 419 Physical Examination, 243, 244, 245, 246, 251, 419 Physiologic, 358, 419, 424, 427 Physiology, 389, 419 Phytohemagglutinins, 405, 419 Pigmentation, 340, 419 Piloerection, 273, 419 Pilot study, 228, 229, 247, 420 Pituitary Gland, 377, 391, 420 Plana, 417, 420, 431 Plant Diseases, 383, 420 Plants, 287, 359, 365, 367, 373, 391, 402, 408, 420, 421, 430, 439 Plasma cells, 267, 281, 362, 411, 420 Plasmin, 420 Plasminogen, 420 Plasminogen Activators, 420 Platelet Activation, 420, 432 Platelet Aggregation, 361, 413, 420, 438 Platelets, 219, 367, 411, 413, 420, 437, 438 Pneumonia, 376, 420 Poisoning, 389, 408, 412, 420 Polyarthritis, 420 Polycystic, 327, 421 Polyethylene, 421, 436 Polyethylene Glycols, 421, 436 Polymerase, 206, 421 Polymerase Chain Reaction, 206, 421 Polymers, 268, 421, 425 Polymethyl Methacrylate, 408, 421 Polymorphism, 421 Polyposis, 374, 421 Polysaccharide, 237, 363, 371, 421, 425 Polyunsaturated fat, 212, 219, 227, 229, 421, 438 Portal Hypertension, 385, 422 Portal Vein, 422 Posterior, 361, 365, 385, 416, 422 Postmenopausal, 359, 415, 422 Postoperative, 6, 422 Postoperative Complications, 422 Postsynaptic, 422, 432, 436 Potentiates, 399, 422 Potentiating, 270, 284, 422 Potentiation, 422, 432 Practice Guidelines, 324, 336, 422 Precursor, 364, 378, 382, 384, 420, 422, 423

Index 437

Predictive factor, 422 Prednisolone, 206, 263, 273, 274, 422 Prednisone, 241, 422 Pregnancy Outcome, 310, 422 Preleukemia, 411, 423, 432 Premedication, 423, 430 Preoperative, 423 Prepuce, 423 Prevalence, 73, 256, 257, 277, 287, 309, 414, 423 Primary Biliary Cirrhosis, 423 Primary Sclerosing Cholangitis, 7, 213, 423 Procollagen, 423 Proctitis, 232, 259, 271, 275, 301, 423 Proctocolectomy, 423 Proctocolitis, 258, 423 Proctosigmoiditis, 275, 301, 423 Proctosigmoidoscopy, 245, 423 Prodrug, 291, 423 Progesterone, 403, 414, 423, 434 Prognostic factor, 424 Progression, 362, 424 Progressive, 211, 276, 277, 278, 288, 289, 371, 373, 392, 411, 415, 420, 424, 429, 440 Progressive disease, 278, 289, 424 Proline, 374, 395, 423, 424 Promoter, 424 Prophylaxis, 6, 256, 257, 265, 424, 441 Prospective study, 404, 424 Prostaglandin, 424, 438 Prostaglandins A, 287, 424 Prostaglandins D, 424 Prostate, 326, 425, 440 Protease, 359, 425 Protein C, 241, 360, 363, 404, 425 Protein S, 264, 299, 327, 328, 368, 378, 390, 425, 435 Proteinuria, 263, 412, 425 Proteoglycans, 366, 425 Proteolytic, 359, 375, 387, 420, 425 Protocol, 72, 245, 249, 250, 251, 425 Proton Pump, 261, 414, 425 Proton Pump Inhibitors, 261, 425 Protons, 359, 395, 401, 425, 427 Protozoa, 376, 402, 409, 425 Protozoan, 371, 390, 406, 425, 439 Proximal, 271, 279, 290, 381, 425 Pseudotumor Cerebri, 401, 426 Psoriasis, 419, 426 Psychic, 407, 426, 431 Psychotherapy, 426 Puberty, 246, 412, 426 Public Health, 299, 324, 426 Public Policy, 323, 426

Pulmonary, 359, 368, 369, 376, 384, 426, 442 Pulse, 308, 409, 426 Pupil, 380, 411, 426 Purpura, 362, 426 Purulent, 357, 426 Pyoderma, 426 Pyoderma Gangrenosum, 426 Pyrazinamide, 270, 284, 426 Q Quality of Life, 6, 72, 240, 242, 247, 276, 277, 300, 301, 340, 426 Quiescent, 269, 426 R Race, 403, 409, 414, 426, 427 Racemic, 403, 414, 427 Radiation, 311, 384, 388, 389, 396, 401, 408, 415, 419, 427, 442 Radiation therapy, 396, 427 Radioactive, 395, 414, 427, 437, 440 Radioimmunotherapy, 427 Radiologist, 313, 427 Radiology, 205, 209, 312, 313, 336, 414, 427 Radiotherapy, 273, 427 Reagent, 386, 401, 427 Receptor, 211, 278, 292, 363, 380, 406, 427, 432 Recombinant, 208, 273, 427 Rectovaginal Fistula, 428 Recur, 300, 428 Red blood cells, 243, 385, 393, 411, 415, 428, 430 Red Nucleus, 365, 428 Reductase, 266, 408, 428 Refer, 1, 369, 375, 381, 388, 394, 404, 413, 427, 428 Refraction, 428, 434 Refractory, 4, 219, 308, 428 Regimen, 246, 249, 382, 428, 429 Regional enteritis, 258, 259, 260, 272, 287, 300, 301, 351, 428 Regurgitation, 390, 428 Relapse, 5, 227, 277, 428 Relative risk, 5, 428 Remission, 4, 5, 205, 206, 207, 208, 210, 211, 218, 221, 224, 225, 226, 240, 243, 248, 249, 275, 276, 277, 286, 287, 288, 300, 310, 313, 406, 428 Renal failure, 429 Reproduction Techniques, 422, 429 Respiration, 409, 429 Restoration, 3, 269, 429, 442 Reticulata, 287, 429 Retina, 429, 430, 431, 441 Retinoblastoma, 326, 429

438 Crohn’s Disease

Retinopathy, 429 Retreatment, 429 Retrospective, 5, 429 Retrospective study, 429 Rheumatism, 396, 429 Rheumatoid, 73, 205, 246, 260, 374, 429 Rheumatoid arthritis, 73, 205, 246, 260, 374, 429 Rigidity, 420, 429 Risk factor, 5, 275, 384, 424, 428, 429 Rituximab, 430 Rod, 366, 402, 430 Rosiglitazone, 240, 430 S Salicylic, 265, 269, 430 Salivary, 378, 380, 416, 430, 435 Salivary glands, 378, 380, 430 Sanitation, 430 Saponins, 430, 434 Sarcoidosis, 430 Sarcoma, 387, 430 Scleroderma, 386, 430 Sclerosis, 327, 374, 410, 430 Scopolamine, 367, 430 Screening, 245, 373, 430 Secretion, 224, 261, 377, 384, 391, 394, 395, 399, 400, 409, 410, 414, 430, 431 Secretory, 414, 430, 436 Sedative, 245, 366, 431 Segregation, 431 Seizures, 417, 431 Semen, 425, 431 Senile, 415, 431 Senna, 235, 431 Sensitization, 431 Sepsis, 205, 304, 431 Septic, 273, 431 Sequencing, 421, 431 Serologic, 431 Serous, 383, 431 Serrata, 417, 431 Seton, 431 Sex Characteristics, 358, 361, 426, 431, 437 Sex Determination, 327, 431 Sex Ratio, 431 Shock, 273, 395, 432, 439 Short Bowel Syndrome, 334, 340, 432 Side effect, 4, 243, 244, 251, 266, 274, 276, 277, 288, 315, 318, 358, 378, 396, 411, 432, 438 Sigmoid, 271, 285, 304, 423, 432 Sigmoid Colon, 423, 432 Sigmoidoscope, 423, 432

Sigmoidoscopy, 240, 242, 275, 301, 313, 354, 432 Signal Transduction, 432 Signs and Symptoms, 428, 432, 440 Skeleton, 401, 424, 432 Skin graft, 432, 434 Small intestine, 259, 266, 271, 276, 285, 288, 292, 313, 337, 341, 370, 373, 382, 384, 390, 395, 396, 401, 412, 428, 432, 439, 442 Smoldering leukemia, 411, 432 Smooth muscle, 361, 394, 432, 435 Soaps, 387, 433 Social Environment, 426, 433 Social Support, 296, 433 Sodium, 227, 274, 391, 409, 433, 436 Sodium Fluoride, 433 Soft tissue, 368, 387, 432, 433 Solitary Rectal Ulcer, 266, 433 Somatic, 358, 395, 409, 418, 433 Sound wave, 427, 433 Soybean Oil, 421, 433 Spastic, 271, 272, 433 Spasticity, 433 Spatial disorientation, 381, 433 Specialist, 343, 380, 433 Specificity, 358, 423, 434 Spectrum, 258, 285, 305, 373, 434 Sperm, 221, 361, 373, 434 Spinal cord, 371, 372, 385, 412, 413, 418, 434 Spleen, 360, 378, 395, 405, 416, 430, 434 Splenic Vein, 422, 434 Spondylitis, 332, 342, 434 Spontaneous Abortion, 422, 434 Sporadic, 269, 429, 434 Standard therapy, 246, 419, 434 Stem Cells, 392, 393, 434 Stenosis, 434, 435 Stents, 434 Sterility, 378, 398, 434 Steroid, 4, 6, 208, 242, 243, 244, 263, 274, 367, 377, 430, 434 Stillbirth, 422, 434 Stimulant, 394, 402, 434 Stimulus, 382, 400, 435 Stomach, 232, 245, 259, 261, 271, 276, 279, 285, 288, 290, 357, 365, 380, 384, 385, 389, 390, 395, 402, 404, 412, 416, 417, 419, 425, 432, 434, 435 Stool, 244, 245, 251, 269, 354, 374, 379, 402, 435 Strand, 421, 431, 435 Streptococcus, 385, 387, 435 Streptomycin, 270, 284, 378, 435

Index 439

Stress, 229, 237, 365, 388, 389, 412, 415, 429, 435, 441 Stricture, 7, 434, 435 Stroke, 253, 322, 435 Stromal, 383, 435 Subacute, 398, 435 Subarachnoid, 392, 435 Subclinical, 5, 398, 431, 435 Subcutaneous, 361, 382, 416, 435 Submaxillary, 384, 435 Subspecies, 226, 433, 435 Substance P, 408, 430, 435 Substrate, 436 Sulfapyridine, 263, 436 Supplementation, 210, 213, 217, 218, 221, 225, 226, 227, 229, 230, 436 Support group, 302, 338, 340, 341, 436 Suppository, 242, 263, 421, 436 Suppression, 377, 436 Sweat, 363, 379, 394, 436 Symphysis, 372, 425, 436 Symptomatic, 265, 282, 362, 416, 436 Synaptic, 413, 432, 436 Synaptic Transmission, 413, 436 Systemic, 73, 242, 260, 274, 278, 280, 289, 291, 316, 317, 360, 363, 368, 374, 398, 401, 422, 427, 430, 436 Systemic lupus erythematosus, 291, 374, 436 T Tachycardia, 366, 436 Tachypnea, 366, 436 Tacrolimus, 436 Technetium, 437 Telangiectasia, 327, 437 Testicle, 246, 391, 437 Testis, 437 Testosterone, 428, 437 Thalamic, 365, 437 Thalamic Diseases, 365, 437 Thalidomide, 318, 437 Thermal, 381, 413, 421, 437 Thioguanine, 292, 437 Thoracic, 210, 365, 437, 442 Thorax, 357, 404, 437 Thrombin, 387, 420, 425, 437, 438 Thrombocytes, 420, 437 Thrombocytopenia, 437 Thromboembolism, 437 Thrombolytic, 420, 437 Thrombomodulin, 425, 438 Thrombophlebitis, 438 Thrombosis, 219, 311, 367, 399, 425, 435, 438 Thromboxanes, 287, 364, 438 Thrombus, 377, 398, 420, 437, 438

Thymus, 397, 405, 438 Thyroid, 391, 438 Thyroid Gland, 391, 438 Tin, 211, 438 Tomography, 376, 438 Topical, 206, 242, 266, 274, 386, 395, 419, 433, 438 Total pancreatectomy, 416, 438 Toxic, iv, 266, 365, 376, 378, 382, 384, 397, 413, 436, 438 Toxicity, 4, 266, 381, 438 Toxicology, 324, 438 Toxins, 266, 363, 398, 427, 438 Trace element, 438, 439 Trachea, 418, 438, 439 Transduction, 432, 439 Transfection, 368, 439 Translation, 360, 439 Translational, 439 Translocation, 439 Transplantation, 7, 373, 382, 397, 406, 439 Trauma, 358, 416, 439 Treatment Failure, 439 Tributyrin, 268, 439 Trichomonas, 415, 439 Trichomonas Infections, 415, 439 Trichomoniasis, 408, 439 Triglyceride, 311, 439 Trivalent, 265, 439 Trophic, 7, 439 Trypsin, 359, 439, 442 Tuberous Sclerosis, 327, 439 Tumor marker, 358, 440 Tumor Necrosis Factor, 3, 4, 218, 251, 260, 268, 280, 437, 440 Tumour, 223, 273, 440 Tunica, 410, 440 U Ulcer, 261, 263, 279, 290, 382, 417, 433, 440 Ulceration, 261, 268, 271, 272, 285, 340, 410, 440 Ultrasonography, 440 Unconscious, 379, 396, 440 Unsaturated Fats, 387, 440 Uraemia, 416, 440 Uranium, 437, 440 Uremia, 429, 440 Ureters, 441 Urethra, 417, 425, 441 Uric, 391, 396, 441 Urinary, 370, 373, 378, 430, 441 Urinary tract, 441 Urine, 218, 243, 244, 246, 251, 362, 368, 384, 393, 425, 441

440 Crohn’s Disease

Urticaria, 362, 441 Uveitis, 232, 417, 441 V Vaccination, 441 Vaccine, 334, 425, 441 Vagina, 355, 379, 402, 428, 441 Vaginal, 317, 385, 436, 441 Vaginal Fistula, 441 Vascular, 264, 278, 289, 361, 379, 383, 393, 398, 404, 409, 413, 420, 438, 441 Vascular endothelial growth factor, 441 Vasculitis, 332, 416, 441 Vasoactive, 264, 441 Vasodilator, 264, 369, 394, 441 Vein, 243, 244, 245, 246, 263, 401, 414, 416, 422, 434, 438, 441 Venous, 367, 393, 425, 441 Ventricle, 426, 442 Ventricular, 72, 442 Vertebrae, 434, 442 Vertebral, 309, 420, 442 Vesicular, 394, 409, 442

Veterinary Medicine, 323, 442 Villi, 442 Villous, 370, 442 Viral, 280, 390, 414, 439, 442 Virulence, 438, 442 Virus, 285, 371, 390, 399, 400, 439, 442 Viscera, 361, 408, 433, 442 Visceral, 365, 402, 418, 442 Vitro, 237, 442 Vivo, 223, 442 W Windpipe, 418, 438, 442 Wound Healing, 399, 442 X Xenograft, 362, 442 X-ray, 245, 246, 251, 285, 354, 366, 376, 377, 388, 389, 406, 414, 427, 442 Y Yeasts, 419, 442 Z Zymogen, 425, 442

Index 441

442 Crohn’s Disease

Index 443

444 Crohn’s Disease

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