CROHN DISEASE A
3-in-1
Medical
Reference
A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers TO INTERNET REFERENCES
CROHN DISEASE A BIBLIOGRAPHY AND DICTIONARY FOR PHYSICIANS, PATIENTS, AND GENOME RESEARCHERS
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. 7404 Trade Street San Diego, CA 92121 USA Copyright ©2007 by ICON Group International, Inc. Copyright ©2007 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 Disease: A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers/ James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-11361-9 1. Crohn 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:
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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 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 Chaired Professor of Management Science 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. 7404 Trade Street San Diego, CA 92121 USA Fax: 858-635-9414 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON CROHN DISEASE ....................................................................................... 3 Overview........................................................................................................................................ 3 Genetics Home Reference ............................................................................................................... 3 What Is Crohn Disease?................................................................................................................. 3 How Common Is Crohn Disease? .................................................................................................. 4 What Genes Are Related to Crohn Disease?.................................................................................. 4 How Do People Inherit Crohn Disease? ........................................................................................ 5 Where Can I Find Additional Information about Crohn Disease? ................................................ 5 References....................................................................................................................................... 6 What Is the Official Name of the CARD15 Gene?......................................................................... 7 What Is the Normal Function of the CARD15 Gene? ................................................................... 7 What Conditions Are Related to the CARD15 Gene? ................................................................... 8 Where Is the CARD15 Gene Located?........................................................................................... 8 References....................................................................................................................................... 9 Federally Funded Research on Crohn Disease ............................................................................. 10 The National Library of Medicine: PubMed ................................................................................ 29 CHAPTER 2. ALTERNATIVE MEDICINE AND CROHN DISEASE ....................................................... 72 Overview...................................................................................................................................... 72 National Center for Complementary and Alternative Medicine.................................................. 72 Additional Web Resources ........................................................................................................... 80 General References ....................................................................................................................... 85 CHAPTER 3. PATENTS ON CROHN DISEASE .................................................................................... 86 Overview...................................................................................................................................... 86 Patent Applications on Crohn Disease ........................................................................................ 86 Keeping Current .......................................................................................................................... 88 CHAPTER 4. BOOKS ON CROHN DISEASE ....................................................................................... 89 Overview...................................................................................................................................... 89 Book Summaries: Online Booksellers........................................................................................... 89 CHAPTER 5. RESEARCHING MEDICATIONS .................................................................................... 92 Overview...................................................................................................................................... 92 U.S. Pharmacopeia....................................................................................................................... 92 Commercial Databases ................................................................................................................. 93 Researching Orphan Drugs ......................................................................................................... 93 APPENDIX A. HELP ME UNDERSTAND GENETICS ......................................................................... 96 Overview...................................................................................................................................... 96 The Basics: Genes and How They Work....................................................................................... 96 Genetic Mutations and Health................................................................................................... 107 Inheriting Genetic Conditions ................................................................................................... 113 Genetic Consultation ................................................................................................................. 121 Genetic Testing .......................................................................................................................... 123 Gene Therapy ............................................................................................................................. 129 The Human Genome Project and Genomic Research................................................................. 132 APPENDIX B. PHYSICIAN RESOURCES ........................................................................................... 135 Overview.................................................................................................................................... 135 NIH Guidelines.......................................................................................................................... 135 NIH Databases........................................................................................................................... 136 Other Commercial Databases..................................................................................................... 139 APPENDIX C. PATIENT RESOURCES .............................................................................................. 140 Overview.................................................................................................................................... 140 Patient Guideline Sources.......................................................................................................... 140
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Finding Associations.................................................................................................................. 144 Resources for Patients and Families........................................................................................... 145 ONLINE GLOSSARIES................................................................................................................ 146 Online Dictionary Directories ................................................................................................... 148 CROHN DISEASE DICTIONARY ............................................................................................. 150 INDEX .............................................................................................................................................. 203
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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 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 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 disease, from the essentials to the most advanced areas of research. Special attention has been paid to present the genetic basis and pattern of inheritance of Crohn disease. 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 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 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. We hope these resources will prove useful to the widest possible audience seeking information on Crohn disease. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/.
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CHAPTER 1. STUDIES ON CROHN DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Crohn disease. For those interested in basic information about Crohn disease, we begin with a condition summary published by the National Library of Medicine.
Genetics Home Reference Genetics Home Reference (GHR) is the National Library of Medicine’s Web site for consumer information about genetic conditions and the genes or chromosomes responsible for those conditions. Here you can find a condition summary on Crohn disease that describes the major features of the condition, provides information about the condition’s genetic basis, and explains its pattern of inheritance. In addition, a summary of the gene or chromosome related to Crohn disease is provided. 2 The Genetics Home Reference has recently published the following summary for Crohn disease:
What Is Crohn Disease?3 Crohn disease is a complex, chronic disorder that primarily affects the digestive system. This condition typically involves abnormal inflammation of the intestinal walls, particularly in the lower part of the small intestine (the ileum) and portions of the large intestine (the colon). Inflammation can occur in any part of the digestive system, however. The inflamed tissues become thick and swollen, and the inner surface of the intestine may develop open sores called ulcers.
2 3
This section has been adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/.
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/condition=crohndisease.
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Crohn disease most commonly appears in a person's late teens or twenties, although the disease can appear at any age. Signs and symptoms tend to flare up (recur) multiple times throughout life. The most common features of this condition are persistent diarrhea, abdominal pain and cramping, loss of appetite, weight loss, and fever. Some people with Crohn disease have chronic bleeding from inflamed tissues in the intestine; over time, this bleeding can lead to a low number of red blood cells (anemia). In some cases, Crohn disease can also cause medical problems affecting the joints, eyes, or skin. Intestinal blockage is a common complication of Crohn disease. Blockages are caused by swelling or a buildup of scar tissue in the intestinal walls. Some affected individuals also develop fistulae, which are abnormal connections between the intestine and other tissues. Fistulae occur when ulcers break through the intestinal wall to form passages between loops of the intestine or between the intestine and nearby structures (such as the bladder, vagina, or skin). Crohn disease is one common form of inflammatory bowel disease (IBD). Another type of IBD, ulcerative colitis, also causes chronic inflammation of the intestinal lining. Unlike Crohn disease, which can affect any part of the digestive system, ulcerative colitis typically causes inflammation only in the colon. In addition, the two disorders involve different patterns of inflammation.
How Common Is Crohn Disease? Crohn disease is most common in western Europe and North America, where it has an estimated incidence of about 7 in 100,000 people. About one million Americans are currently affected by this disorder. Crohn disease occurs more often in Caucasians (whites) and people of eastern and central European (Ashkenazi) Jewish descent than among people of other ethnic backgrounds.
What Genes Are Related to Crohn Disease? Variations of the CARD15 (http://ghr.nlm.nih.gov/gene=card15) gene increase the risk of developing Crohn disease. A variety of genetic and environmental factors likely play a role in causing Crohn disease. Although researchers are studying risk factors that may contribute to this complex disorder, most of these factors remain unknown. Cigarette smoking is thought to increase the risk of developing this disease, and it may also play a role in periodic flare-ups of signs and symptoms. Studies suggest that Crohn disease may result from a combination of certain gene variations, changes in the immune system, and the presence of bacteria in the digestive tract. Most of the genetic changes have not been identified, although variations in one gene, CARD15, have been strongly associated with an increased risk of developing Crohn disease in the ileum. This increased risk has been found only in Caucasian populations. The CARD15 gene provides instructions for making a protein that helps protect the intestinal lining from bacterial infection. Changes in this gene prevent cells in the intestine from responding normally to bacteria, which may lead to the chronic inflammation characteristic of Crohn disease.
Studies
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Several other genes are under study as possible risk factors for Crohn disease. Additional research is needed to determine what role these genes play in the development of this disorder.
How Do People Inherit Crohn Disease? The inheritance pattern of Crohn disease is unclear because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having an affected family member is a significant risk factor for the disease.
Where Can I Find Additional Information about Crohn Disease? You may find the following resources about Crohn disease helpful. These materials are written for the general public. NIH Publications - National Institutes of Health •
National Center for Biotechnology Information: Genes and Disease: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.116
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National Institute of Diabetes and Digestive and Kidney Diseases: http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/ MedlinePlus - Health Information
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Encyclopedia: Crohn's disease: http://www.nlm.nih.gov/medlineplus/ency/article/000249.htm
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Health Topic: Crohn's Disease: http://www.nlm.nih.gov/medlineplus/crohnsdisease.html
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Tutorials: Crohn's Disease: http://www.nlm.nih.gov/medlineplus/tutorials/crohnsdisease/htm/index.htm Educational Resources - Information Pages
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American Academy of Family Physicians: http://familydoctor.org/810.xml
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American Gastroenterological Association: http://www.gastro.org/wmspage.cfm?parm1=851
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Children's Hospital Boston: http://www.childrenshospital.org/az/Site2135/mainpageS2135P0.html
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Cincinnati Children's Hospital Medical Center: http://www.cincinnatichildrens.org/health/info/abdomen/diagnose/crohns.htm
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Cleveland Clinic Health Information Center: http://www.clevelandclinic.org/health/search/showdocuments.asp?mediaID=5&topicId=154&sortId=2
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KidsHealth from the Nemours Foundation: http://kidshealth.org/parent/medical/digestive/ibd.html
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Madisons Foundation: http://www.madisonsfoundation.org/content/3/1/display.asp?did=313
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Mayo Clinic: http://www.mayoclinic.org/crohns/
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Merck Manual of Medical Information, Second Home Edition: http://www.merck.com/mmhe/sec09/ch126/ch126b.html
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Orphanet: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=206 Patient Support - for Patients and Families
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American Autoimmune Related Diseases Association: http://www.aarda.org/
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Crohn's & Colitis Foundation of America: http://www.ccfa.org/
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National Organization for Rare Disorders: http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Crohn\
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Resource list from the University of Kansas Medical Center: http://www.kumc.edu/gec/support/gastroen.html Professional Resources
You may also be interested in these resources, which are designed for healthcare professionals and researchers. •
Gene Tests - DNA tests ordered by healthcare professionals: http://www.genetests.org/query?testid=173599
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ClinicalTrials.gov - Linking patients to medical research: http://clinicaltrials.gov/search/condition=%22Crohn+disease%22?recruiting=false
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PubMed - Recent literature: http://ghr.nlm.nih.gov/condition=crohndisease/show/PubMed;jsessionid=C3AF9CAC CC2528AB1A7DF7CB86A7C617
•
OMIM - Genetic disorder catalog: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=266600
References These sources were used to develop the Genetics Home Reference condition summary on Crohn disease. •
Chamberlin WM, Naser SA. Integrating theories of the etiology of Crohn's disease. On the etiology of Crohn's disease: questioning the hypotheses. Med Sci Monit. 2006 Feb;12(2):RA27-33. Epub 2006 Jan 26. Review. PubMed citation
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•
Gasche C, Grundtner P. Genotypes and phenotypes in Crohn's disease: do they help in clinical management? Gut. 2005 Jan;54(1):162-7. Review. No abstract available. Erratum in: Gut. 2005 Mar;54(3):442. PubMed citation
•
Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, Lees W, Novelli M, Bloom S, Segal AW. Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet. 2006 Feb 25;367(9511):668-78. PubMed citation
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Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002 Aug 8;347(6):417-29. Review. No abstract available. PubMed citation
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Russell RK, Nimmo ER, Satsangi J. Molecular genetics of Crohn's disease. Curr Opin Genet Dev. 2004 Jun;14(3):264-70. Review. PubMed citation
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Schreiber S, Rosenstiel P, Albrecht M, Hampe J, Krawczak M. Genetics of Crohn disease, an archetypal inflammatory barrier disease. Nat Rev Genet. 2005 May;6(5):376-88. Review. PubMed citation
•
Stange EF, Travis SP, Vermeire S, Beglinger C, Kupcinkas L, Geboes K, Barakauskiene A, Villanacci V, Von Herbay A, Warren BF, Gasche C, Tilg H, Schreiber SW, Scholmerich J, Reinisch W; European Crohn's and Colitis Organisation. European evidence based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis. Gut. 2006 Mar;55 Suppl 1:i1-15. No abstract available. PubMed citation
•
Vermeire S, Rutgeerts P. Current status of genetics research in inflammatory bowel disease. Genes Immun. 2005 Dec;6(8):637-45. Review. PubMed citation
A summary of the gene related to Crohn disease is provided below:
What Is the Official Name of the CARD15 Gene?4 The official name of this gene is “caspase recruitment domain family, member 15.” CARD15 is the gene's official symbol. The CARD15 gene is also known by other names, listed below.
What Is the Normal Function of the CARD15 Gene? The CARD15 gene provides instructions for making a protein called caspase recruitment domain family member 15 or, more commonly, NOD2. The NOD2 protein is active in some types of immune system cells (including monocytes, macrophages, and dendritic cells), which help protect the body against foreign invaders such as viruses and bacteria. The NOD2 protein is also active in several types of cells found in the lining of the intestine. These cells play an important role in defending the intestinal wall against bacterial infection. Many types of bacteria commonly live in the digestive system. Most of them are harmless, such as bacteria in the intestine that normally help digest food. Other bacteria, however, can infect the body and cause disease. The NOD2 protein is involved in recognizing certain 4
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=card15;jsessionid=C3AF9CACCC2528AB1A7DF7CB86A7C617.
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bacteria in the intestine and stimulating the immune system to respond properly. In response to specific substances produced by bacteria, NOD2 activates a protein complex called nuclear factor-kappa-B. This protein complex regulates the activity of multiple genes, including genes that control immune responses and inflammatory reactions. By activating nuclear factor-kappa-B, the NOD2 protein helps protect the digestive tract from bacterial invasion.
What Conditions Are Related to the CARD15 Gene? Crohn Disease - Increased Risk from Variations of the CARD15 Gene More than 60 variations in the CARD15 gene have been associated with an increased risk of Crohn disease in the lower part of the small intestine (the ileum). This increased risk has been found only in Caucasian (white) populations. The most common variation, written as 3020insC or 1007fs, leads to the production of a NOD2 protein that is slightly shorter than normal. Other common variations replace one protein building block (an amino acid) with a different amino acid in the NOD2 protein. All of these genetic changes appear to disrupt the protein's protective role in the digestive tract. Researchers believe that changes in the CARD15 gene prevent the NOD2 protein from recognizing bacteria, allowing these microbes to grow unchecked and invade cells lining the intestine. An abnormal immune response to these bacteria may lead to chronic inflammation and the digestive problems characteristic of Crohn disease. Cancers - Associated with the CARD15 Gene More than 60 variations in the CARD15 gene have been associated with an increased risk of Crohn disease in the lower part of the small intestine (the ileum). This increased risk has been found only in Caucasian (white) populations. The most common variation, written as 3020insC or 1007fs, leads to the production of a NOD2 protein that is slightly shorter than normal. Other common variations replace one protein building block (an amino acid) with a different amino acid in the NOD2 protein. All of these genetic changes appear to disrupt the protein's protective role in the digestive tract. Researchers believe that changes in the CARD15 gene prevent the NOD2 protein from recognizing bacteria, allowing these microbes to grow unchecked and invade cells lining the intestine. An abnormal immune response to these bacteria may lead to chronic inflammation and the digestive problems characteristic of Crohn disease. Other Disorders - Associated with the CARD15 Gene A few studies have suggested a possible association between changes in the CARD15 gene, particularly the common variation 3020insC, and the development of certain cancers. Although some of these studies found an increased risk of cancer in people with a CARD15 variation, other research found no such association.
Where Is the CARD15 Gene Located? Cytogenetic Location: 16q21
Studies
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Molecular Location on chromosome 16: base pairs 49,288,550 to 49,324,487
The CARD15 gene is located on the long (q) arm of chromosome 16 at position 21. More precisely, the CARD15 gene is located from base pair 49,288,550 to base pair 49,324,487 on chromosome 16.
References These sources were used to develop the Genetics Home Reference gene summary on the CARD15 gene. •
Buhner S, Buning C, Genschel J, Kling K, Herrmann D, Dignass A, Kuechler I, Krueger S, Schmidt HH, Lochs H. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation? Gut. 2006 Mar;55(3):342-7. Epub 2005 Jul 6. PubMed citation
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Eckmann L, Karin M. NOD2 and Crohn's disease: loss or gain of function? Immunity. 2005 Jun;22(6):661-7. Review. PubMed citation
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Elmaagacli AH, Koldehoff M, Hindahl H, Steckel NK, Trenschel R, Peceny R, Ottinger H, Rath PM, Ross RS, Roggendorf M, Grosse-Wilde H, Beelen DW. Mutations in innate immune system NOD2/CARD 15 and TLR-4 (Thr399Ile) genes influence the risk for severe acute graft-versus-host disease in patients who underwent an allogeneic transplantation. Transplantation. 2006 Jan 27;81(2):247-54. PubMed citation
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Gasche C, Grundtner P. Genotypes and phenotypes in Crohn's disease: do they help in clinical management? Gut. 2005 Jan;54(1):162-7. Review. No abstract available. Erratum in: Gut. 2005 Mar;54(3):442. PubMed citation
•
Holler E, Rogler G, Herfarth H, Brenmoehl J, Wild PJ, Hahn J, Eissner G, Scholmerich J, Andreesen R. Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood. 2004 Aug 1;104(3):889-94. Epub 2004 Apr 15. PubMed citation
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Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):599-603. PubMed citation
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•
Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S, Fuji A, Yuasa T, Manki A, Sakurai Y, Nakajima M, Kobayashi H, Fujiwara I, Tsutsumi H, Utani A, Nishigori C, Heike T, Nakahata T, Miyachi Y. Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood. 2005 Feb 1;105(3):1195-7. Epub 2004 Sep 30. PubMed citation
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Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, Chamaillard M, Zouali H, Thomas G, Hugot JP. CARD15 mutations in Blau syndrome. Nat Genet. 2001 Sep;29(1):19-20. PubMed citation
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Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):603-6. PubMed citation
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Rogler G, Holler E. Can NOD2/CARD15 mutations predict intestinal graft-versus-host disease and aid our understanding of Crohn's disease? Nat Clin Pract Gastroenterol Hepatol. 2004 Dec;1(2):62-3. No abstract available. PubMed citation
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Russell RK, Nimmo ER, Satsangi J. Molecular genetics of Crohn's disease. Curr Opin Genet Dev. 2004 Jun;14(3):264-70. Review. PubMed citation
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Schreiber S. Slipping the barrier: how variants in CARD15 could alter permeability of the intestinal wall and population health. Gut. 2006 Mar;55(3):308-9. Review. No abstract available. PubMed citation
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Schurmann M, Valentonyte R, Hampe J, Muller-Quernheim J, Schwinger E, Schreiber S. CARD15 gene mutations in sarcoidosis. Eur Respir J. 2003 Nov;22(5):748-54. PubMed citation
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Vermeire S, Rutgeerts P. Current status of genetics research in inflammatory bowel disease. Genes Immun. 2005 Dec;6(8):637-45. Review. PubMed citation
•
Wang X, Kuivaniemi H, Bonavita G, Mutkus L, Mau U, Blau E, Inohara N, Nunez G, Tromp G, Williams CJ. CARD15 mutations in familial granulomatosis syndromes: a study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathy. Arthritis Rheum. 2002 Nov;46(11):3041-5. PubMed citation
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Watanabe T, Kitani A, Strober W. NOD2 regulation of Toll-like receptor responses and the pathogenesis of Crohn's disease. Gut. 2005 Nov;54(11):1515-8. Review. No abstract available. PubMed citation
Federally Funded Research on Crohn Disease The U.S. Government supports a variety of research studies relating to Crohn disease. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.5
5
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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CRISP (Computerized Retrieval of Information on Scientific Projects) CRISP 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 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 disease. The following is typical of the type of information found when searching the CRISP database for Crohn disease: •
Project Title: CROHN'S DISEASE GENE MAPPING OF CHROMOSOME 16 Principal Investigator & Institution: Brant, Steven R.; Professor of Gastroenterology; Medicine; Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680 Timing: Fiscal Year 2005; Project Start 01-MAY-2001; Project End 28-FEB-2007 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 pathophysiology of this enigmatic disease, improve genetic counseling and make possible novel preventative and therapeutic strategies.
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Project Title: CROHN'S DISEASE: MICROFLORA ANALYSIS AND HOST RESPONSE Principal Investigator & Institution: Relman, David A.; Associate Professor of Medicine; Microbiology and Immunology; Stanford University 1215 Welch Road, Mod B Stanford, Ca 943055402
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Timing: Fiscal Year 2005; Project Start 01-SEP-2002; Project End 30-JUN-2007 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. •
Project Title: DIETARY TREATMENT OF CROHN'S DISEASE Principal Investigator & Institution: Mutlu, Ece A.; Internal Medicine; Rush University Medical Center 1653 W Congress Pkwy Chicago, Il 60612 Timing: Fiscal Year 2005; Project Start 01-SEP-2005; Project End 31-AUG-2008 Summary: (provided by applicant): Our long-term objective is to show that CAM techniques can improve management of inflammatory bowel disease (ibd) which includes Ulcerative Colitis (UC) and Crohn's Disease (CD). Our immediate objective is to determine whether a specific dietary intervention or a fructooligosaccharide (FOS) supplement has anti-oxidant or prebiotic effects and whether it is beneficial in the treatment of CD. Supporting a strong link between diet and CD, several epidemiological studies and therapeutic observations in the complementary and alternative medicine (CAM) literature suggest that diet is key to development of CD and its treatment. We took advantage of these CAM recommendations and designed a diet encompassing recommendations common to these CAM systems with particular attention to increasing the intake of dietary foodstuffs that have antioxidant and prebiotic effects. Using this diet together with a FOS supplement, our preliminary studies showed that our diet intervention is acceptable and well-tolerated and results in improvement of 66% of patients, reducing symptoms and/or the degree of inflammation. This finding now needs to be validated by a study with a stronger design, and the mechanisms underlying the effects of dietary manipulation-such as potential effects on microfloraneed to be elucidated. In another pilot study using amplicon length heterogeneity, we demonstrated that the intestinal microflora of patients with CD differ significantly from healthy individuals. Whether we can normalize the microflora of CD patients, however, remains to be determined. Accordingly, we designed a study to test the hypotheses that: (1) dietary manipulation with either diet or a FOS supplement is an effective CAM therapy that prevents CD relapse (leads to maintenance of remission) and (2) such dietary manipulation can normalize the microflora of CD patients and decrease mucosal oxidative damage. Aim 1. To determine in a pilot, open-label study, whether dietary
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manipulation with a specific dietary therapy (that encompasses recommendations of various CAM practices) or a FOS supplement prevents flare-up in patients with inactive CD. Aim 2. To determine a) whether the same dietary manipulation with a specific dietary therapy or FOS normalizes colonic microflora and prevents mucosal oxidative damage in CD; and b) whether the observed changes correlate with clinical maintenance of remission. Significance. This study could provide information to suggest diet as a safe therapy for IBD and lay the groundwork for more definitive, randomized, controlled trials. •
Project Title: EFFECTS OF NALTREXONE ON ACTIVE CROHN'S DISEASE Principal Investigator & Institution: Smith, Jill P.; Professor; Medicine; Pennsylvania State Univ Hershey Med Ctr Office of Research Affairs H138 Hershey, Pa 170330850 Timing: Fiscal Year 2006; Project Start 01-AUG-2006; Project End 31-JUL-2008 Summary: (provided by applicant): Crohn's disease is a chronic relapsing and remitting condition causing inflammation of the bowel. The major symptoms of Crohn's disease include abdominal pain, diarrhea, gastrointestinal bleeding, malabsorption, and weight loss. The etiology of Crohn's disease is unknown. Biopsies obtained from the bowel in subjects with Crohn's disease reveal inflammatory cells suggesting that the bowel is either reacting immunologically to a stimulus or the endogenous immune system of the gastrointestinal track is off balance. The treatment of IBD always has been directed toward inflammation. Drugs (e.g., steroids or azathioprine) are used to decrease the inflammatory response in the bowel by suppressing the host immune system. Most recently, anti-tumor necrosis factor (TNF) strategies for Crohn's disease have developed, and a new era of treatment with specific immunotherapy has been developed. These medications are chimeric antibodies that are extremely expensive and have potential side effects. Our research in the basic science laboratory has involved studying the endogenous opioid systems (i.e., enkephalins and endorphins, and opioid receptors), and their role on growth and wound healing. We have shown in a mouse with chemically-induced colitis that naltrexone significantly decreases inflammation of the bowel and improves the inflammatory index. A pilot study tested the clinical response to oral naltrexone in subjects with active Crohn's disease and found significant improvement in the Crohn's Disease Activity Index (CDAI) as well as endoscopic reversal of inflammation. It is hypothesized that oral naltrexone will improve inflammation of the bowel by increasing endogenous enkephalin levels in subjects with active Crohn's disease. In order to test this hypothesis, 40 subjects with active Crohn's disease will be randomized to receive either oral naltrexone (4.5 mg) or placebo daily for 3 months. Subjects' response will be monitored by the CDAI scores, endoscopy, histology, and quality of life surveys. After 3 months of therapy all subjects will be treated in an open-labeled fashion to test the longevity of response and determine if 6 months of therapy is better than 3 months. Durability of response will be evaluated in a 1-month follow-up. This trial is based upon novel innovative preclinical and clinical data and may lead to a larger multi-center trial in the future.
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Project Title: GENES AS IMMUNOPHENOTYPIC SUBGROUPS OF CROHN'S DISEASE Principal Investigator & Institution: Rotter, Jerome I.; Principle Investigator; CedarsSinai Medical Center 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2005; Project Start 30-SEP-2005; Project End 31-AUG-2010 Summary: It has been apparent for some years that a major etiologic risk factor for Crohn's disease (CD) is genetic susceptibility. There is clear increased familial
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aggregation and a number of genetic loci have been identified by genome-wide scans. A major advance was the identification of NOD2/CARD15 as the IBD1 gene, as it implicated the importance of the innate immune system in CD. However, while a number of genes are being identified that predispose to CD, we still know little of the genetic factors that determine the severity. Investigators in this PPG have demonstrated that the presence and magnitude of multiple CD-associated antibodies (ASCA, OMPC, 12) are associated with a more aggressive CD phenotype (termed CD-HighR). We have also demonstrated that at least one of these antibodies, ASCA, is familial, and while linked to specific regions of the genome, it is not linked/associated with NOD2/CARD15 in our data. The goal of this project is to identify the genes that underlie the expression of CD associated serum antibodies and the phenotypic spectrum of CD. We will use a large scale candidate gene approach, with the likely most relevant immunologic pathways (innate immunity, Th1 effector cells, regulatory T and B cells, and co-stimulatory pathways) being elucidated by other Projects in this PPG. To undertake such an approach we need the capability to do large scale genotyping, and to have both hypothesis generating and confirming stages. Both technology and patient resources are now available. Aim 1 is the hypothesis generating step, in which we will proceed to the identification of putative susceptibility genes for immuno-phenotypic subgroups of CD by performing a comprehensive association study in a case/control design. We will study approximately 225-300 genes, for an average of 10 markers per gene, which will be analyzed by a haplotype based approach that captures the common variation in a gene. The genes will be tested against the individual quantitative antibody levels and quartile sums. This will involve testing over 2300 markers, which will be accomplished using the high throughput technology of Illumina Corporation. Aim 2, is the hypothesis confirmatory step, in which the 15 "best" genes from Aim 1 will be tested in a second panel of subjects, an independent family based panel of CD "trios" (affected CD patients and both parents), that also numbers 1200 subjects. In Aim 3, the 3-5 best genes from Aim 2 will be sequenced for additional variation by examining individuals who are simultaneously from the extremes of the antibody distribution and share associated haplotypes of the associated candidate genes. Because of the resources of this PPG, this project provides a unique opportunity to identify genes that determine the severity of CD, thus providing insight into biological pathways potentially leading to improved therapeutics and even prevention. •
Project Title: GENETIC STUDIES IN CROHN'S DISEASE Principal Investigator & Institution: Achkar, Jean-Paul; Medicine; Cleveland Clinic Lerner Col/Med-Cwru 9500 Euclid Avenue Cleveland, Oh 44195 Timing: Fiscal Year 2005; Project Start 15-SEP-2005; Project End 31-AUG-2010 Summary: (provided by applicant): This application is designed to provide Jean-Paul Achkar, MD with a program of mentored, patient-oriented research. The proposed plan of education and training would allow the PI to build on a foundation of research that he has pursued to date and to further develop his research career with the ultimate goal of becoming an independent funded clinical investigator in inflammatory bowel disease genetics. This training would include class work at Case Western Reserve University with the goal of obtaining a Masters degree. This proposal outlines an approach to address our central hypotheses that: 1. defining more homogeneous subgroups of Crohn's disease (CD) will help in finding CD-susceptibility genes and in understanding underlying pathogenesis of CD, 2. phenotypic information can be used to identify more homogeneous subgroups of CD and 3. similar to findings with NOD2/CARD15 variants, abnormalities in innate host defense involving Paneth cells account for susceptibility to CD in different patient subgroups. We propose to address these
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hypotheses by conducting initiatives aimed at identifying more homogeneous CD subgroups by: 1. using an unbiased genetic approach of analyzing stratified genomewide linkage, and 2. performing directed candidate gene studies of Paneth cell products. Our specific aims are: Aim #1: Collect detailed phenotypic information on CD-affected individuals for whom we already have genotypic data from genome scans and then perform stratified genome-wide linkage analyses. Stratification will be based on defining subsets of CD-affected individuals by specific phenotypic parameters. Through collaborative efforts, the PI has access to a large IBD genome scan dataset. The PI will perform detailed phenotyping of CD-affected relative pairs who were part of this genome scan dataset. We will then perform genome-wide linkage analyses of data subsets defined by specific phenotypic parameters. Aim #2: Perform a candidate gene, case-control, haplotype-based association study to identify mutations in Paneth cell products that may predispose to the development of CD in subgroups of patients. The PI will continue to recruit patients and controls for an IBD DMA bank that he recently started. This collection will then be used to pursue a case-control, haplotype-based analysis of Paneth cell candidate genes. •
Project Title: HLA AND KIR IN RHEUMATOID ARTHRITIS AND CROHN'S DISEASE Principal Investigator & Institution: Erlich, Henry A.; Senior Scientist; Children's Hospital & Res Ctr at Oakland 747 52Nd St Oakland, Ca 946091809 Timing: Fiscal Year 2005; Project Start 20-SEP-2005; Project End 28-FEB-2010 Summary: (provided by applicant): The association of specific alleles and haplotypes at the HLA class I and class II loci with a variety of autoimmune diseases is well established. Recently, polymorphisms in the Killer Immunoglobulin-like Receptors (KIR) genes that encode the stimulatory and inhibitory receptors on NK cells have been reported to be associated with a few of the same HLA-associated diseases, (e.g. psoriatic arthritis, scleroderma, and T1D). The ligands recognized by many of these receptors are epitopes on HLA class I molecules. Our goal is to carry out case/control association analyses for Crohn's Disease and Rheumatoid Arthritis using our high resolution HLA and KIR genotyping methods. We have developed high throughput, robust, and high resolution immobilized probe methods for genotyping the HLA class I and class II loci and a high throughput MALDI-TOF method for genotyping the KIR loci. Specific DRB1 alleles have already been associated with each of these diseases (DRB1*0103 for CD and DRB1*0401 and *0404 for RA) but we will evaluate the role of other HLA loci in these diseases. HLA class I typing is also critical in evaluating the role of the KIR genes since the association data must be stratified on the presence or absence of the HLA epitope ligand to examine the effects of KIR-HLA combinations. In addition, we will genotype another well-established disease gene polymorphism, the PTNP22 locus, allowing stratification of the HLA and KIR association data. The analyses of HLA-KIR in population-based studies will add significantly to our understanding of the role of the innate immune system in these complex autoimmune disorders.
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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 2005 Summary: This abstract is not available.
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Project Title: IBD:TNF-ALPHA INFLAMMATION
AND
CROHN'S
DISEASE
MUCOSAL
Principal Investigator & Institution: Targan, Stephan R.; Director; Cedars-Sinai Medical Center 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2005; Project Start 15-AUG-1999; Project End 31-JUL-2009 Summary: (provided by applicant): Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract characterized by an imbalanced TH1 response. IFN-gamma, TNF, and three members of the TNF superfamily (CD40, OX40 and LIGHT) are known to be key factors in the development or regulation of mucosal inflammation in rodents. Production of both TNF and IFN-gamma is exaggerated in the mucosa of patients with Crohn's disease. The effectiveness of agents that bind TNF for the treatment of Crohn's disease is evidence that TNF has an important role in Crohn's disease mucosal inflammation. A very recent pilot study using blocking antibodies to IFN-gamma suggested a dose-dependent, attenuation of disease activity in Crohn's disease patients, implying a major role for mucosal IFN-gamma in disease initiation and severity. Our studies on potentiation of IFN-gamma, production by TNF provided evidence for the existence of a soluble factor(s), produced by LPMC, which augmented IFN-gamma production by activated T-cells, acting independently of IL-12 and IL-18, as well as in synergy with them. The TNF-like molecule (TL1A) is a strong candidate for this factor. TL1A has a predicted N-terminal transmembrane domain and binds the TNF-family receptor, DR3, for which no other ligand had been identified. TL1A augments activation-induced IFN-gamma production, in both PB and LP T-cells, independently of, yet in synergy with IL-12 and IL-18. In contrast to resting PB T-cells, small fractions of Tcells from control and ulcerative colitis mucosa stain for membrane -TL1A and for DR3. In contrast, markedly larger fractions of LP CD4+ T-cells from active Crohn's disease lesions are membrane TL1A (mbTL1A) and DR3 positive. In addition, TL1A mRNA in active lesions of Crohn's disease mucosa is elevated several-fold above normal. Furthermore, only in cells from Crohn's disease lesions is IFN-? production by stimulated LP T-cells partially inhibited by anti-TL1A monoclonal antibody. These data suggest that this TNF-family cytokine plays an important role in increasing the level of IFN-? in Crohn's disease mucosa. Our overall hypothesis is that TL1A and its receptor DR3 act to increase the severity of Crohn's disease pathology by potentiating IFN-? production by LP CD4 T-cells, independently of, or in conjunction with IL-12 and IL-18. We will begin address this hypothesis by 1) determining the cellular events involved in augmentation of IFN-? protein production by TL1A and/or IL-12 and IL-18; 2) determining the molecular events that lead to augmentation of IFN-gamma mRNA expression by TL1A and/or IL-12 and IL-18; and 3) identifying the cellular and molecular mechanisms responsible for increased TL1A expression in Crohn's disease mucosa. •
Project Title: IMMUNOBIOLOGY OF DENDRITIC CELLS IN CROHN'S DISEASE Principal Investigator & Institution: Smythies, Lesley E.; Medicine; University of Alabama at Birmingham 1530 3Rd Avenue South Birmingham, Al 35294 Timing: Fiscal Year 2005; Project Start 30-SEP-2005; Project End 31-AUG-2007 Summary: (provided by applicant): The regulation of macrophage and dendritic cell (DC) responses to ingested antigens and luminal microorganisms is a critical component of homeostasis in the intestinal muosa. We have reported that resident macrophages in normal human intestine are profoundly down-regulated for inflammatory responses due to exposure to mucosal stromal cell products, particularly TGF-beta (Smythies, et al. J. Clin. Invest. 115:66, '05). This down-regulation likely contributes to the near absence of
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inflammation in normal small intestine. Regarding intestinal DCs, our preliminary results suggest that resident DCs in normal human small intestinal mucosa are less prevalent, express lower levels of maturation and activation markers, and release lower levels of cytokines than DCs in the non-inflamed mucosa of patients with Crohn's disease. Thus, DCs in normal intestinal mucosa, like intestinal macrophages, may be down-regulated for inflammatory activity, suggesting that intestinal DCs also contribute to the low level of inflammation in normal intestinal mucosa, DCs in non-inflamed intestinal mucosa of patients with Crohn's disease may be less stringently downregulated and thus able to promote inflammation. Our preliminary results suggest that intestinal lamina propria stroma releases factors that down-regulate the maturity and inflammatory potential of monocyte-derived DCs (M-DCs), indicating a possible mechanism by which intestinal DCs, which likely are derived from the circulation, become down-regulated for inflammatory activity in normal intestinal mucosa. Therefore, to confirm and extend our preliminary results, we propose in this application to test the following two hypotheses: (1) Primary human intestinal DCs from patients with Crohn's disease are more prevalent, more mature and more activated than DCs from normal intestine and (2) The reduced level of maturity and activation of DCs in normal intestinal mucosa compared to that of DCs in Crohn's disease intestinal mucosa is due to intestinal stromal factors on DCs recruited from the circulation into the lamina propria. Using homologous primary intestinal DCs and M-DCs, we propose to test the above hypotheses with the following two Specific Aims: 1. Determine whether small intestinal DCs from patients with Crohn's disease are more prevalent, more mature and more activated than DCs from normal intestine, enabling DCs from Crohn's disease tissue to present antigen more efficiently than DCs from normal intestinal tissue. 2. Determine whether the reduced level of maturity and activation of DCs from normal intestinal mucosa compared to DCs from Crohn's disease mucosa is due to the effects of intestinal stromal factors on DCs. •
Project Title: IMURAN DOSE RANGING STUDY IN CROHN'S DISEASE Principal Investigator & Institution: Sands, Bruce E.; Assistant Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2005; Project Start 30-SEP-2005; Project End 29-SEP-2007 Summary: Abstract Not Provided
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Project Title: MECHANISMS OF BONE LOSS IN PEDIATRIC CROHN DISEASE Principal Investigator & Institution: Sylvester, Francisco A.; St. Francis Hosp/Med Ctr (Hartford, Ct) 114 Woodland Street Hartford, Ct 061051299 Timing: Fiscal Year 2005; Project Start 01-SEP-2004; Project End 31-JUL-2009 Summary: (provided by applicant): Our application proposes to examine the mechanisms by which bone formation is impaired in pediatric Crohn disease. Crohn disease is a chronic inflammatory disorder of the gastrointestinal tract. Bone mineral density is decreased in about 50% of patients at the time of diagnosis, before exposure to corticosteroids. Our studies have shown that biochemical markers of bone turnover are significantly decreased in newly diagnosed children with Crohn disease. We hypothesize that bone formation is reduced in these children, We believe that this is secondary to the inflammatory response present in this disorder. In Crohn disease, CD4+Thl cells are characteristically activated and secrete interferon (IFN)-gamma, among other products. We have shown that IFN-gamma plays a critical role in the inhibition of osteoblast differentiation and function in vitro by activated T cells. We hypothesize that IFN-g blocks the signal transduction of bone morphogenetic protein
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(BMP)-2, a critical factor in early osteoblast development. Our specific aims are: 1. To examine calcium (Ca) absorption, excretion, and incorporation into bone in newly diagnosed children with Crohn disease using stable Ca isotopes. Concurrently we will determine bone mineral density, measure biochemical markers of osteoblast activity and bone matrix degradation and then correlate these parameters with clinical variables such as the pediatric Crohn disease activity index and IFN-gamma synthesis by activated T cells from the peripheral circulation and inflamed colon. 2. To examine the effects of IFN-gamma on components of the BMP-2 signaling cascade in cells of the osteoblast lineage obtained from mice with chronic colonic inflammation (Interleukin-10 knockout mice) and in a mouse bone marrow stromal cell line (ST-2 cells). Our studies will involve a unique collaboration of experts in pediatric gastroenterology, bone cell biology, signal transduction, and human nutrition and will provide important insight into the mechanisms of bone loss in Crohn disease and other childhood diseases characterized by abnormal T cell activation. •
Project Title: MECHANISMS OF EXPERIMENTAL CROHN'S DISEASE Principal Investigator & Institution: Cominelli, Fabio; Director, Digestive Health Center of Exc; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195 Timing: Fiscal Year 2005; Project Start 01-JUL-1999; Project End 30-APR-2007 Summary: (provided by applicant): Crohn's disease (CD) is a debilitating condition of unknown etiology that is poorly responsive to currently available treatments. A working hypothesis suggests that CD may represent a dysregulated immune response to antigens derived from normal intestinal bacteria in a genetically predisposed host. Our studies will take advantage of a new strain of mice referred to as SAMP1/Yit/FC that develops enteritis spontaneously without genetic or immunologic manipulations. Preliminary studies indicate that these mice develop disease only when colonized with normal murine intestinal flora and not when derived under germfree conditions. The central hypothesis of this proposal is that in SAMP1/Yit/FC mice, normal intestinal bacteria are required for the development of ileitis through the induction of antigenspecific immune responses in the gut, and that proper manipulation of the bacterial flora may result in disease amelioration. The overall objective of this proposal is to investigate, in a mechanistic fashion, the role of the bacterial flora in experimental CD. In order to achieve our goals we will: 1) Determine the effects of antibiotic/probiotic administration on the severity of ileitis. The effects of antibiotic administration, as well as that of well-characterized probiotics will be investigated. In addition, the ability of antibiotic/probiotic treatment to maintain remission following initial treatment with anti-TNF or prednisone will be studied; 2) Characterize the composition of the bacterial flora as well as its functional effects on T cell activation. State-of-the-art techniques, including 16S rRNA PCR will be used to characterize the bacterial flora colonizing the ileum versus the colon of SAMP1IYitJFC mice. In addition, a series of in vitro T-cell activation studies as well as adoptive transfer experiments following stimulation with indigenous flora will be used to attempt to define the pathogenesis of ileitis in these mice; 3) Determine the effects of germ-free conditions and the role of specific bacterial species on chronic intestinal inflammation. SAMP1/Yit/FC mice will be re-derived under specific germ-free conditions and specific bacterial species will be re-introduced to determine their ability to induce chronic ileitis in germ-free mice. In addition, adoptive transfer experiments will be performed to define whether the primary abnormality of SAMP1/Yit/FC mice occurs in the T cells or is caused by specific bacterial antigens.
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Project Title: MUCOSAL T-CELLS IN EARLY&LATE PEDIATRIC CROHN'S DISEASE Principal Investigator & Institution: Kugathasan, Subra; Pediatrics; Medical College of Wisconsin 8701 Watertown Plank Rd Milwaukee, Wi 532260509 Timing: Fiscal Year 2005; Project Start 01-APR-2001; Project End 31-MAR-2007 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 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.
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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 2004; Project Start 01-JUL-2003; Project End 30-APR-2009 Summary: (provided by applicant): Azathioprine (AZA) is an effective steroid-sparing therapy for chronically active Crohn's Disease (CD) and prevents relapse of steroid-
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induced 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 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. •
Project Title: MYCOBACTERIUM AVIUM SUBSPECIES IN CROHN'S DISEASE Principal Investigator & Institution: Naser, Saleh A.; Molecular Biol & Microbiology; University of Central Florida 12201 Research Parkway, Suite 501 Orlando, Fl 328263231 Timing: Fiscal Year 2005; Project Start 01-JUN-2002; Project End 31-MAY-2007 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
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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 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. •
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 Street, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2005; Project Start 08-APR-2002; Project End 31-JAN-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
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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. •
Project Title: POLYPEPTIDE CONFORMATION AND INTERACTION WITH HSP70 Principal Investigator & Institution: Cavagnero, Silvia; Chemistry; University of Wisconsin Madison Suite 6401 Madison, Wi 537151218 Timing: Fiscal Year 2005; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The goal of this proposal is to elucidate the conformation of N-terminal polypeptides of increasing length (belonging to the sequence of an all-alpha-helical single domain model protein) in the presence of the cotranslationally active chaperone Hsp70. In order to obtain information at amino-acid specific resolution, multidimensional NMR in the presence of isotopically labeled peptide and unlabeled chaperone will be employed. Other biophysical methods such as isothermal titration calorimetry, size exclusion chromatography and fluorescence spectroscopy will also be used. The work focuses on elongating N-terminal polypeptides derived from apomyoglobin, a relatively small and extremely well characterized system which serves as an excellent model for all-alpha-helical proteins. The proposed investigations will explore whether Hsp70 merely prevents interchain aggregation by holding a statistical coil status, or it also acts by inducing specific polypeptide conformations. This study is not intended to directly mimic intracellular cotranslational and immediately posttranslational folding events. On the other hand, it aims at providing a first order in vitro approximation to how Hsp70 is able to affect the
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conformational space of elongating polypeptides. The expected influence of specific cellrelated effects such as polypeptide tethering (to the ribosome exit channel) and molecular crowding are discussed in the proposal and will be addressed by separate additional experiments. Very little is known about the mechanisms by which Hsp70, the main cotranslationally active chaperone, influences the course of protein folding. Yet, progress is urgently needed in this area since defective action (or insufficient bioavailable amount) of cotranslational chaperones has been linked to the formation of incorrectly folded self-associated species such as those involved in a number of deadly diseases. These include cystic fibrosis, inflammatory heart disease, Crohn disease, P53related cancers, and several neurodegenerative disorders such as Huntington's and Alzheimer's disease. Experiments to be carried out include (a) high resolution secondary structure mapping of isotopically labeled polypeptides by NMR in the presence of unlabeled Hsp70 chaperone; (b) hydrogen/deuterium exchange pulse labeling kinetic experiments to detect the mechanisms of structure formation in the presence of Hsp70; (c) additional studies in the presence of the Hsp40 and Hsp70-nucleotide exchange factor cochaperones. •
Project Title: PROTEIN AND ENERGY USE IN PEDIATRIC CROHN'S DISEASE Principal Investigator & Institution: Steiner, Steven J.; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2006; Project Start 28-SEP-2006; Project End 30-JUL-2011 Summary: (provided by applicant): More than one-third of children with Crohn's disease suffer from growth failure. Given the rising incidence and earlier diagnosis of Crohn's disease, nutrition and growth are critical outcomes for these children. There is a lack of knowledge concerning the response of these parameters to new therapies for Crohn's disease. Infliximab, an anti-tumor necrosis factor-alpha antibody, has revolutionized the care of children with Crohn's disease recalcitrant to corticosteroid therapy or complicated by fistulizing disease. We hypothesize that children with active Crohn's disease will have increased energy expenditure and proteolysis, and that treatment with infliximab will lead to greater improvement in these parameters than traditional corticosteroid therapy. To test these hypotheses, children with active relapsed Crohn's disease will be enrolled in a prospective study. Outpatient metabolic studies will be conducted just before, tow and fourteen weeks after initiation of corticosteroid of infliximab therapy. Using stable essential amino acid isotopes, rates of total body proteolysis and albumin synthesis can be measured in fasting, and enterally and parenterally fed states. Resting energy expenditure, using indirect calorimetry, and total energy expenditure, using doubly-labeled water, will be calculated at each visit. The proposed work is innovative, as it expands the knowledge of protein and energy use in response to traditional and novel therapies for pediatric Crohn's disease. These results will also help allow children with Crohn's disease to reach their true growth potential. The principal investigator, having completed a Masters of Science in Clinical Research, is in an established clinical research environment with a sponsor experienced in metabolic studies in children. Future training in nutrition and metabolic techniques are planned to further the principal investigator's education. This study will allow the principal investigator the opportunity to continue to develop clinical research skills in a mentored environment, with the expectation to expand these studies as an independent investigator in the future.
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Project Title: RECOMBINANT HUMAN DEFENSIN FOR MANAGEMENT OF ILEAL CROHN'S DISEASE Principal Investigator & Institution: Huang, Ning; Ventria Bioscience 4110 N Freeway Blvd Sacramento, Ca 958341219 Timing: Fiscal Year 2006; Project Start 01-AUG-2006; Project End 30-APR-2007 Summary: (provided by applicant): Inflammatory bowel disease (IBD), including Crohn's disease, is a chronic inflammation of the intestine, for which current therapies are inadequate. In industrialized countries, Crohn's disease affects about 1 in 500 individuals, and it is estimated that about one million Americans suffer from some form of IBD. Current hypotheses suggest that in the pathogenesis of all forms of IBD, intestinal microbes trigger inflammatory disease in genetically susceptible individuals. Over the past decade, epithelial cells of the intestine, and other tissues, have been identified as a source of defensins and other antimicrobial peptides. These molecules contribute to innate host defense of epithelial surfaces. One antimicrobial peptide expressed by epithelial cells of the human small intestine, human defensin-5 (HD5), is the prime focus of experiments in this grant proposal. Recent investigations provide strong evidence that deficient expression of HD5 is a predisposing factor for Crohn's disease of the ileum. Human defensins are currently not available commercially. Our aims seek to use a protein expression system, ExpressTec, which has been developed by Ventria Bioscience, to produce HD5 using cereal grains. Our proposed studies will yield a commercial source of HD5 that could be used to augment the deficient levels of this molecule in the intestine of ileal Crohn's disease patients. Thus, our efforts may result in a novel therapeutic strategy for the treatment of IBD,
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Project Title: ROLE OF IL-18 IN CROHN'S DISEASE (CD) Principal Investigator & Institution: Pizarro, Theresa T.; Associate Professor of Medicine; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 229044195 Timing: Fiscal Year 2005; Project Start 01-JUL-2000; Project End 31-AUG-2010 Summary: (provided by applicant): Although the precise etiology is unknown, inflammatory bowel disease (IBD) is thought to occur as a result of a dysregulated mucosal immune response to environmental factors in a genetically predisposed individual. IL-18 is a cytokine that plays an important role in the pathogenesis of several chronic Th1-mediated disorders, including Crohn's disease (CD). In fact, a dramatic shift in IL-18 expression occurs during CD from intestinal epithelial cells (IEC) to mucosal immune cells (i.e. macrophages and dendritic cells), as the severity of disease increases. In addition, recent evidence supports the role of IL-18 as a protective factor during the acute phase of mucosal immune responses, when IEC are the primary source of IL-18. This novel function for IL-18 contrasts with the pathogenic role IL-18 is believed to play in more chronic phases of Th1-mediated inflammation. A genetic basis for differences in IL-18 regulation and expression observed in IBD may exist since recent studies have reported the association of specific single nucleotide polymorphisms (SNPs) in the IL-18 promoter region and several autoimmune diseases. Therefore, using genetic and molecular biology techniques as well as experimental models intestinal inflammation, the present study is designed to investigate the specific genetic factors that regulate IL-18 synthesis and to determine the precise function of epithelial and immune cell-derived IL-18 in the acute versus chronic phases of IBD. The central hypothesis of the present proposal is that IL-18 plays a key role in regulating normal innate immune responses in the gut mucosa and dysregulation of IL-18 may result in chronic intestinal inflammation characteristic of IBD. The following three specific aims
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are proposed to test this hypothesis: 1) Determine the relationship between polymorphisms in the IL-18 promoter region and IBD. The role of IL-18 in IBD susceptibility will be defined using an association approach by screening for recently described IL-18 promoter polymorphisms and performing case association studies of these genetic markers in well-characterized IBD and control populations. IBD multiplex families will also be used to test linkage disequilibrium between these marker loci and putative disease susceptibility loci in order to further characterize the transmission pattern of allelic variants. 2) Define the mechanism(s) of polymorphic IL-18 gene regulation in different mucosal cell populations. The functional relevance of IL-18 promoter polymorphisms will be achieved by creation of reporter constructs, sitedirected mutagenesis experiments, and in vitro transfection assays in epithelial and macrophage cell lines. In addition, differential transcription factor binding and subsequent transcriptional regulation will be assessed in order to determine how the IL18 gene is differentially regulated by IL-18 promoter polymorphisms, and if transcriptional control varies among different intestinal cell types. 3) Evaluate the specific role of IL-18 derived from different gut mucosal cell populations in an in vivo setting using experimental models of intestinal inflammation. The extent and severity of disease will be assessed in mice genetically- and immunologically-manipulated to produce IL-18 in either hematopoietic- (i.e. immune cells) or non-hematopoietic-cells (i.e. epithelial cells) following the induction of acute or chronic intestinal inflammation. These experiments will mechanistically address, in an in vivo setting, if IL-18 derived from specific mucosal cell populations and expressed during the acute versus chronic phases of disease, are involved in the pathogenesis of IBD. 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. •
Project Title: ROLE OF INFECTIOUS AGENTS IN PEDIATRIC CROHN'S DISEASE Principal Investigator & Institution: Gold, Benjamin D.; Associate Professor; Pediatrics; Emory University 1784 North Decatur Road, Suite 510 Atlanta, Ga 30322 Timing: Fiscal Year 2005; Project Start 15-AUG-2004; Project End 31-JUL-2007 Summary: This R03 proposal will develop and standardize an appropriate clinical and laboratory approach to investigating potential infectious etiologies of pediatric Crohn's disease (CD). We aim to standardize specimen procurement, processing and testing with unique, validated laboratory assays to detect select infectious agents in pediatric intestinal biopsies, and evaluate the appropriateness of different control specimens. Future studies to test whether infection(s) cause pediatric CD or determine its morbidity demand these tools and methods. CD pathobiology is unclear. It has been proposed that one or more infectious agents precipitate CD in a genetically susceptible host and it may be easier to identify some agents in childhood CD. Current scientific evidence does not prove causality, despite research on a number of specific microbes (e.g., enteroadherent Escherichiae coli, measles virus). To test infectious hypotheses, valid diagnostic tools must be developed and tested in well-characterized cohorts of children as well as adults employing uniform case and control definitions. Differences between childhood and adult onset CD might signify risk factor differences: children can have more severe intestinal disease, increased risk of colon cancer and earlier complication onset. Children, particularly with new onset disease, may represent a unique population to study environmental factors (e.g., infection), since younger age brings shorter and less complicated exposure histories to confound analyses. The Pediatric IBD Consortium of 6 large, geographically diverse U.S. centers represents an excellent platform to investigate potential infectious triggers of CD, evaluating and recording clinical and epidemiologic
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data on approximately 288 newly diagnosed pediatric CD cases per year in a comprehensive database. Our application proposes that adequate collection of intestinal biopsies from uniformly-defined Consortium cases and controls and validation of sensitive and specific laboratory tools to detect potential infectious triggers of CD in such specimens can be achieved. Our R03 aims to: 1) standardize collection (e.g., anatomic source), processing and banking of gastrointestinal biopsies obtained during clinically-indicated endoscopy of well-characterized children with CD and wellcharacterized controls; 2) define, standardize and verify "appropriate" controls, "nondiseased" biopsies from cases vs. clinically-indicated biopsies from children without IBD (e.g., Hirschsprung's disease); 3) standardize and validate detection of certain infectious agents in these specimens through pathology-based (IHC, ISH), broad-range amplification-based (PCR) and organism-specific (e.g., MAP) molecular analysis complemeted by culture for MAP and localization of pathogens within diseased tissue. Parallel comparisons of intestinal biopsies to gene arrays on stool specimes from cases and controls to ascertain the role of indigenous colonic microflora will also be performed. Subsequent prospective application of methods and systems developed by this proposal to the uniquely large, well characterized Consortium cohort will optimize detecting differences between CD and non-disease. •
Project Title: ROLES OF NOD2 IN THE PATHOGENESIS OF CROHN'S DISEASE Principal Investigator & Institution: Flavell, Richard A.; Professor and Chairman; Immunobiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2005; Project Start 15-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): Crohn's disease is a common illness of the gastrointestinal tract with a prevalence of approximately 0.1-0.2% in many developed countries; it affects approximately half a million Americans. It had been postulated that genetic mechanisms contribute to the pathogenesis of Crohn's disease. The recent finding that mutations of the Nod2 gene are observed in Crohn's disease patients at a high frequency has been one of the great successes of molecular medicine in the inflammatory bowel disease (IBD) field. However this finding by itself cannot make possible prevention or treatment of Crohn's disease since we do not know the mechanism whereby mutation of Nod2 gene leads to susceptibility to the disease. Recently, we found that Nod2 signaling requires the kinase, Rip2/Rick using Rip2 deficient mice. Our goal in this proposal is to elucidate IBD disease mechanisms by using genetically manipulated mice. There are two conceivable scenarios through which mutation of Nod2 could play a role in disease pathogenesis, namely loss or gain of function of Nod2. At this stage both mechanisms are possible. Therefore, by using two different strains of mice, Nod2 deficient mice and Nod2 transgenic mice, we will address this question and try to reveal the underlying mechanisms whereby Nod2 mutation contributes to Crohn's disease. Furthermore, by using mice in which Rip2, the kinase downstream of Nod2, is deficient, we will try to reveal if the IBD pathology caused by Nod2 mutation is dependent on Rip2.
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Project Title: THE NATURAL HISTORY OF PEDIATRIC CROHN'S DISEASE Principal Investigator & Institution: Dubinsky, Marla C.; Cedars-Sinai Medical Center 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2005; Project Start 01-FEB-2004; Project End 30-NOV-2008 Summary: (provided by applicant): This award will afford the candidate an opportunity to acquire the clinical research training, educational tools, scientific techniques and mentorship that will be instrumental for her to succeed as an
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independent investigator in Pediatric IBD research as well as an important contributor to the field of IBD. The career development plan will include didactic learning through the K30 program, local GCRC training and training in the ethical conduct of research as well as the research activities proposed in the research plan. Environment: With the protected time afforded by the K23 award and the institutional commitment, the candidate will be able to devote 75% of her time to the didactic component (K30 program) and to completing the scientific proposal described below The mentors for this award bring with an expertise critical to the success of the career and research plan. The Director of Common Diseases Genetics at Cedars-Sinai will provide the training and resources to acquire a solid understanding of genetic research and the Director of the Immunobiology Institute at Cedars-Sinai, will provide the opportunities to incorporate newfound knowledge in the field of immunology into the proposed research and will direct the immune work to be done in this project. Additionally the GCRC will provide the resources and facilities that will be necessary to conduct all genetic testing. Research: Childhood-onset Crohn's disease is often described as having an aggressive clinical course such that patients develop disease complications early in the disease course, often necessitating aggressive medical and/or surgical management. This project proposes that there are identifiable risk factors that determine or predict a more aggressive disease course of Crohn's disease in children. The objective is to conduct a prospective longitudinal cohort study to define the natural history of childhood-onset Crohn's disease and to analyze the demographic, genetic, immune and environmental influences on aggressive disease phenotypes and disease progression. The specific aims of this project are 1) to establish a clinically well characterized patient cohort from the Western Region of North America to study disease progression or natural history of children with new-onset Crohn's disease and 2) To determine if there are identifiable demographic, genetic, immunologic and/or environmental risk factors that influence aggressive disease phenotypes and disease progression in children with new-onset Crohn's disease. A total of 400 patients from the Western Region of North America will be enrolled. Principal procedures will include data collection on clinical and environmental history as well as blood sampling for genotyping and testing immune response. Collected data will be stored in a secured relational pediatric IBD database. Primary outcome measures include frequency and time to occurrence of complicating disease behaviors and the associations between markers of risk and defined patient outcome. Defining the natural history of childhood-onset Crohn's disease and delineating the potential determinants of aggressive disease progression will lead to long term efforts to define the preclinical natural history of the disease, and to develop intervention studies to prevent progression of clinical disease to clinical complications. •
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 770303498 Timing: Fiscal Year 2005; Project Start 01-MAY-2002; Project End 30-APR-2007 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
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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. •
Project Title: TREATMENT OF CROHN'S DISEASE WITH GROWTH HORMONE Principal Investigator & Institution: Hannon, Tamara S.; Children's Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 152132583
Hosp
Timing: Fiscal Year 2005; 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.
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Crohn disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type Crohn disease (or synonyms) into the search box, and click Go. The following is the type of output you can expect from PubMed for Crohn disease (hyperlinks lead to article summaries): •
A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Author(s): Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL, Reinisch W, Teml A, Schwab M, Lichter P, Radlwimmer B, Stange EF. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16909382&query_hl=14&itool=pubmed_docsum
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A comment. Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease. Author(s): Nielsen P. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15513372&query_hl=14&itool=pubmed_docsum
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A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease. Author(s): Levine A, Weizman Z, Broide E, Shamir R, Shaoul R, Pacht A, Dinari G, On A, Weiss B, Bujanover Y; Israeli Pediatric Gastroenterology Association Budesonide Study Group. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12548062&query_hl=14&itool=pubmed_docsum
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A Gly15Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease. Author(s): van der Linde K, Boor PP, Sandkuijl LA, Meijssen MA, Savelkoul HF, Wilson JH, de Rooij FW. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12825869&query_hl=14&itool=pubmed_docsum
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A group-based patient education programme for high-anxiety patients with Crohn disease or ulcerative colitis. Author(s): Larsson K, Sundberg Hjelm M, Karlbom U, Nordin K, Anderberg UM, Loof L. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12889564&query_hl=14&itool=pubmed_docsum
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A novel approach to a patient with Crohn disease and a high stoma output: a missed opportunity? Author(s): Jones S, Shannon H, Srivastava E, Haboubi N. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15125476&query_hl=14&itool=pubmed_docsum
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A novel NOD2/CARD15 haplotype conferring risk for Crohn disease in Ashkenazi Jews. Author(s): Sugimura K, Taylor KD, Lin YC, Hang T, Wang D, Tang YM, FischelGhodsian N, Targan SR, Rotter JI, Yang H. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12577202&query_hl=14&itool=pubmed_docsum
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A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric Crohn disease. Author(s): Cezard JP, Nouaili N, Talbotec C, Hugot JP, Gobert JG, Schmitz J, Mougenot JF, Alberti C, Goulet O. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12717087&query_hl=14&itool=pubmed_docsum
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Abscesses in Crohn disease: percutaneous drainage. Author(s): Casola G, vanSonnenberg E, Neff CC, Saba RM, Withers C, Emarine CW. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3823434&query_hl=14&itool=pubmed_docsum
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Absence of human herpesvirus 8 in sarcoidosis and Crohn disease granulomas. Author(s): Knoell KA, Hendrix JD Jr, Stoler MH, Patterson JW, Montes CM. Source: Archives of Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16027317&query_hl=14&itool=pubmed_docsum
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Acceleration of linear growth following intestinal resection for Crohn disease. Author(s): Lipson AB, Savage MO, Davies PS, Bassett K, Shand WS, Walker-Smith JA. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2209659&query_hl=14&itool=pubmed_docsum
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Active Crohn disease: CT findings and interobserver agreement for enteric phase CT enterography. Author(s): Booya F, Fletcher JG, Huprich JE, Barlow JM, Johnson CD, Fidler JL, Solem CA, Sandborn WJ, Loftus EV Jr, Harmsen WS. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17032911&query_hl=14&itool=pubmed_docsum
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Activity of Crohn disease assessed by measurement of superior mesenteric artery flow with Doppler US. Author(s): van Oostayen JA, Wasser MN, van Hogezand RA, Griffioen G, de Roos A. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7972778&query_hl=14&itool=pubmed_docsum
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Activity of Crohn disease: value of Color-Power-Doppler and contrast-enhanced ultrasonography. Author(s): Robotti D, Cammarota T, Debani P, Sarno A, Astegiano M. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15162232&query_hl=14&itool=pubmed_docsum
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Acute massive rectal bleeding as a presenting sign of Crohn disease. Author(s): Smith-Behn J, Banez A, Brown T, Simon R, Lin P. Source: N Y State J Med. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3265996&query_hl=14&itool=pubmed_docsum
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Adenocarcinoma of the ileum in Crohn disease. Author(s): Tirkes AT, Duerinckx AJ. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15891804&query_hl=14&itool=pubmed_docsum
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Altered bone mass in children at diagnosis of Crohn disease: a pilot study. Author(s): Harpavat M, Greenspan SL, O'Brien C, Chang CC, Bowen A, Keljo DJ. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15750387&query_hl=14&itool=pubmed_docsum
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An atypical presentation of Crohn disease in the elderly. A case report and Literature review. Author(s): Percivale A, Mattia S, Pasqualini M, Pittaluga M, Paroldi A, Pellicci R. Source: G Chir. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12886751&query_hl=14&itool=pubmed_docsum
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Anorectal strictures and genital Crohn disease: an unusual clinical association. Author(s): Saadah OI, Oliver MR, Bines JE, Stokes KB, Cameron DJ. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12604983&query_hl=14&itool=pubmed_docsum
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Anti-inflammatory and growth-stimulating effects precede nutritional restitution during enteral feeding in Crohn disease. Author(s): Bannerjee K, Camacho-Hubner C, Babinska K, Dryhurst KM, Edwards R, Savage MO, Sanderson IR, Croft NM. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15076624&query_hl=14&itool=pubmed_docsum
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Anti-interleukin-12 antibody treatment for Crohn disease: potential risk of invasive disease due to mycobacteria and salmonellae infection. Author(s): MacLennan C, Lammas DA, Kumararatne DS. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15825052&query_hl=14&itool=pubmed_docsum
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Aphthoid ulcers in Crohn disease: radiographic course and relationship to bowel appearance. Author(s): Ni XY, Goldberg HI. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3945729&query_hl=14&itool=pubmed_docsum
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Are activated T cells regulators of bone metabolism in children with Crohn disease? Author(s): Sylvester FA, Davis PM, Wyzga N, Hyams JS, Lerer T. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16647405&query_hl=14&itool=pubmed_docsum
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Assessment of small bowel Crohn disease: noninvasive peroral CT enterography compared with other imaging methods and endoscopy--feasibility study. Author(s): Wold PB, Fletcher JG, Johnson CD, Sandborn WJ. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12944602&query_hl=14&itool=pubmed_docsum
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Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn disease. Author(s): Yamazaki K, Takazoe M, Tanaka T, Ichimori T, Saito S, Iida A, Onouchi Y, Hata A, Nakamura Y. Source: Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15503241&query_hl=14&itool=pubmed_docsum
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Association of inosine triphosphatase 94C>A and thiopurine S-methyltransferase deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study. Author(s): von Ahsen N, Armstrong VW, Behrens C, von Tirpitz C, Stallmach A, Herfarth H, Stein J, Bias P, Adler G, Shipkova M, Oellerich M, Kruis W, Reinshagen M, Schutz E. Source: Clinical Chemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16214825&query_hl=14&itool=pubmed_docsum
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Association of TNF-alpha polymorphisms in Crohn disease. Author(s): Zipperlen K, Peddle L, Melay B, Hefferton D, Rahman P. Source: Human Immunology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15620462&query_hl=14&itool=pubmed_docsum
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Atopic manifestations are more common in patients with Crohn disease than in the general population. Author(s): Myrelid P, Dufmats M, Lilja I, Grinn C, Lannerstad O, Sjodahl R. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15513357&query_hl=14&itool=pubmed_docsum
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Atypical presentation of Crohn disease in an Asian-Indian patient. Author(s): Nigwekar SU, Casey KJ. Source: Southern Medical Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17195440&query_hl=14&itool=pubmed_docsum
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Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Author(s): Pearson DC, May GR, Fick GH, Sutherland LR. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7778826&query_hl=14&itool=pubmed_docsum
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Bacterial flagellin is a dominant antigen in Crohn disease. Author(s): Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, Fort M, Hershberg RM. Source: The Journal of Clinical Investigation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15124021&query_hl=14&itool=pubmed_docsum
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Ballet dancer with hip and groin pain: Crohn disease and psoas abscess. Author(s): Sauer C, Gutgesell M. Source: Clinical Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16211200&query_hl=14&itool=pubmed_docsum
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Bilateral lid margin ulcers as the initial manifestation of Crohn disease. Author(s): Diaz-Valle D, Benitez del Castillo JM, Fernandez Acenero MJ, Pascual Allen D, Moriche Carretero M. Source: American Journal of Ophthalmology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15289143&query_hl=14&itool=pubmed_docsum
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Bladder involvement in Crohn disease: role of CT in detection and evaluation. Author(s): Merine D, Fishman EK, Kuhlman JE, Jones B, Bayless TM, Siegelman S. Source: Journal of Computer Assisted Tomography. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2910953&query_hl=14&itool=pubmed_docsum
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Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn disease and experimental colitis in vivo. Author(s): Atreya R, Mudter J, Finotto S, Mullberg J, Jostock T, Wirtz S, Schutz M, Bartsch B, Holtmann M, Becker C, Strand D, Czaja J, Schlaak JF, Lehr HA, Autschbach F, Schurmann G, Nishimoto N, Yoshizaki K, Ito H, Kishimoto T, Galle PR, Rose-John S, Neurath MF. Source: Nature Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10802717&query_hl=14&itool=pubmed_docsum
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Blocking lymphocyte adhesion: new treatment for sticky cases of Crohn disease? Author(s): Rhee SJ, Bousvaros A. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12916502&query_hl=14&itool=pubmed_docsum
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Body composition in Crohn disease patients: is it a contradictory issue? Author(s): Capristo E, Addolorato G, Mingrone G, Greco AV, Gasbarrini G. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10232883&query_hl=14&itool=pubmed_docsum
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Body-composition alterations consistent with cachexia in children and young adults with Crohn disease. Author(s): Burnham JM, Shults J, Semeao E, Foster BJ, Zemel BS, Stallings VA, Leonard MB. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16087987&query_hl=14&itool=pubmed_docsum
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Bone density reduction in patients with Crohn disease and associations with demographic and disease variables: cross-sectional data from a population-based study. Author(s): Haugeberg G, Vetvik K, Stallemo A, Bitter H, Mikkelsen B, Stokkeland M. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11444476&query_hl=14&itool=pubmed_docsum
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Bone loss in children with Crohn disease: Evidence of "osteoimmune" alterations. Author(s): Gordon CM. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16647398&query_hl=14&itool=pubmed_docsum
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Bowel ultrasound in Crohn disease: current role and future applications. Author(s): Parente F, Maconi G, Bianchi Porro G. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12229959&query_hl=14&itool=pubmed_docsum
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Carcinoma of the small intestine and colon as a complication of Crohn disease: radiologic manifestations. Author(s): Kerber GW, Frank PH. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6695061&query_hl=14&itool=pubmed_docsum
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CARD15 mutations are rare in Swedish pediatric Crohn disease. Author(s): Idestrom M, Rubio C, Granath F, Finkel Y, Hugot JP. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15795594&query_hl=14&itool=pubmed_docsum
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Chemokine production by buccal epithelium as a distinctive feature of pediatric Crohn disease. Author(s): Damen GM, Hol J, de Ruiter L, Bouquet J, Sinaasappel M, van der Woude J, Laman JD, Hop WC, Buller HA, Escher JC, Nieuwenhuis EE. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16456405&query_hl=14&itool=pubmed_docsum
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Chronobiological aspects of adult-onset Crohn disease. Author(s): Mikulecky M, Rovensky J, Kmecova Z. Source: Wiener Klinische Wochenschrift. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16053199&query_hl=14&itool=pubmed_docsum
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Computed tomography evaluation of the sacroiliac joints in Crohn disease. Radiologic/clinical correlation. Author(s): Scott WW Jr, Fishman EK, Kuhlman JE, Caskey CI, O'Brien JJ, Walia GS, Bayless TM. Source: Skeletal Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2333561&query_hl=14&itool=pubmed_docsum
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Computed tomography in Crohn disease. Author(s): Frager DH, Goldman M, Beneventano TC. Source: Journal of Computer Assisted Tomography. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6886133&query_hl=14&itool=pubmed_docsum
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Computed tomography in the evaluation of Crohn disease. Author(s): Goldberg HI, Gore RM, Margulis AR, Moss AA, Baker EL. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6600342&query_hl=14&itool=pubmed_docsum
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Computed tomography vs barium studies in the acutely symptomatic patient with Crohn disease. Author(s): Orel SG, Rubesin SE, Jones B, Fishman EK, Bayless TM, Siegelman SS. Source: Journal of Computer Assisted Tomography. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3680682&query_hl=14&itool=pubmed_docsum
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Concurrent development of Crohn disease and myelodysplastic syndrome in a child: case report and literature review. Author(s): Nahas SC, Nahas CS, Marques CF, Borba MR, Helito AS, Odoni V. Source: Pediatric Hematology and Oncology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16849278&query_hl=14&itool=pubmed_docsum
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Conservative surgery in Crohn disease. Author(s): Harrison RA, Clark CG. Source: Surg Annu. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3510467&query_hl=14&itool=pubmed_docsum
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Contemporary morphologic definition of backwash ileitis in ulcerative colitis and features that distinguish it from Crohn disease. Author(s): Goldstein N, Dulai M. Source: American Journal of Clinical Pathology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16880149&query_hl=14&itool=pubmed_docsum
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Corneal perforation due to severe peripheral ulcerative keratitis in Crohn disease. Author(s): Tan MH, Chen SD, Rubinstein A, Bron AJ. Source: Cornea. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16783157&query_hl=14&itool=pubmed_docsum
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Crohn disease and intravenous immunoglobulin G. Author(s): Knoflach P, Muller C, Eibl MM. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2306068&query_hl=14&itool=pubmed_docsum
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Crohn disease and the myelodysplastic syndrome. Author(s): Boberg KM, Brinch L, Vatn M. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7847659&query_hl=14&itool=pubmed_docsum
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Crohn disease in an infant with central nervous system thrombosis and proteinlosing enteropathy. Author(s): Mezoff AG, Cohen MB, Maisel SK, Farrell MK. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2202803&query_hl=14&itool=pubmed_docsum
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Crohn disease in systemic lupus erythematosus: a case report. Author(s): Nagata M, Ogawa Y, Hisano S, Ueda K. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2663509&query_hl=14&itool=pubmed_docsum
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Crohn disease in the elderly. Author(s): Feczko PJ, Barbour J, Halpert RD, Ackerman LV. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4048436&query_hl=14&itool=pubmed_docsum
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Crohn disease in the pediatric patient: CT evaluation. Author(s): Jabra AA, Fishman EK, Taylor GA. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2014299&query_hl=14&itool=pubmed_docsum
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Crohn disease obstruction of the biliopancreatic limb in a patient operated for biliopancreatic diversion for morbid obesity. Author(s): Pretolesi F, Camerini G, Marinari GM, Stabilini C, Capaccio E. Source: Emerg Radiol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16362811&query_hl=14&itool=pubmed_docsum
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Crohn disease of the ileocecal region: US visualization of the appendix. Author(s): Puylaert JB, van der Werf SD, Ulrich C, Veldhuizen RW. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3277243&query_hl=14&itool=pubmed_docsum
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Crohn disease of the small bowel: preliminary comparison among CT enterography, capsule endoscopy, small-bowel follow-through, and ileoscopy. Author(s): Hara AK, Leighton JA, Heigh RI, Sharma VK, Silva AC, De Petris G, Hentz JG, Fleischer DE. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16373764&query_hl=14&itool=pubmed_docsum
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Crohn disease of the small intestine: accuracy and relevance of enteroclysis. Author(s): Maglinte DD, Chernish SM, Kelvin FM, O'Connor KW, Hage JP. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1620862&query_hl=14&itool=pubmed_docsum
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Crohn disease of the small intestine: diffuse mucosal granularity. Author(s): Glick SN, Teplick SK. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3966117&query_hl=14&itool=pubmed_docsum
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Crohn disease with sclerosing cholangitis and liver cirrhosis in adolescence. Author(s): Ramelli GP, Tonz O, Zimmermann A, Lentze MJ. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1954960&query_hl=14&itool=pubmed_docsum
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Crohn disease. Author(s): Dworken HJ. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6742651&query_hl=14&itool=pubmed_docsum
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Crohn disease: early recognition and progress of aphthous lesions. Author(s): Hizawa K, Iida M, Kohrogi N, Kuroki F, Yao T, Sakamoto K, Fujishima M. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8284398&query_hl=14&itool=pubmed_docsum
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Crohn Disease: mural attenuation and thickness at contrast-enhanced CT Enterography--correlation with endoscopic and histologic findings of inflammation. Author(s): Bodily KD, Fletcher JG, Solem CA, Johnson CD, Fidler JL, Barlow JM, Bruesewitz MR, McCollough CH, Sandborn WJ, Loftus EV Jr, Harmsen WS, Crownhart BS. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16436815&query_hl=14&itool=pubmed_docsum
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Crohn disease: perirectal and perianal findings at CT. Author(s): Yousem DM, Fishman EK, Jones B. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3357940&query_hl=14&itool=pubmed_docsum
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Crohn disease: prone-angled compression view in radiographic evaluation. Author(s): Yue NC, Jones B. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8475310&query_hl=14&itool=pubmed_docsum
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Cutaneous Crohn disease in a child. Author(s): Pinna AL, Atzori L, Ferreli C, Aste N. Source: Pediatric Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16445412&query_hl=14&itool=pubmed_docsum
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Dermatologic manifestations of Crohn disease in children: response to infliximab. Author(s): Kugathasan S, Miranda A, Nocton J, Drolet BA, Raasch C, Binion DG. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12883301&query_hl=14&itool=pubmed_docsum
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Development of Crohn disease during anti-TNF-alpha therapy in a child with juvenile idiopathic arthritis. Author(s): Ruemmele FM, Prieur AM, Talbotec C, Goulet O, Schmitz J. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15269630&query_hl=14&itool=pubmed_docsum
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Development of lymphoma in patients with Crohn disease. Author(s): Glick SN, Teplick SK, Goodman LR, Clearfield HR, Shanser JD. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6484163&query_hl=14&itool=pubmed_docsum
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Diagnosis and treatment of perianal fistulas in Crohn disease. Author(s): Schwartz DA, Pemberton JH, Sandborn WJ. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11712881&query_hl=14&itool=pubmed_docsum
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Diagnosis of fistulae and sinus tracts in patients with Crohn disease: value of MR imaging. Author(s): Koelbel G, Schmiedl U, Majer MC, Weber P, Jenss H, Kueper K, Hess CF. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2705359&query_hl=14&itool=pubmed_docsum
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Diarrhea after misoprostol in Crohn disease. Author(s): Faich GA, Frick MF, Koffer H. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1899013&query_hl=14&itool=pubmed_docsum
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Direct or indirect association in a complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn disease. Author(s): Fisher SA, Hampe J, Onnie CM, Daly MJ, Curley C, Purcell S, Sanderson J, Mansfield J, Annese V, Forbes A, Lewis CM, Schreiber S, Rioux JD, Mathew CG. Source: Human Mutation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16835882&query_hl=14&itool=pubmed_docsum
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DLG5 variants contribute to Crohn disease risk in a Canadian population. Author(s): Newman WG, Gu X, Wintle RF, Liu X, van Oene M, Amos CI, Siminovitch KA. Source: Human Mutation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16450402&query_hl=14&itool=pubmed_docsum
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Doppler US in patients with Crohn disease: vessel density in the diseased bowel reflects disease activity. Author(s): Spalinger J, Patriquin H, Miron MC, Marx G, Herzog D, Dubois J, Dubinsky M, Seidman EG. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11110944&query_hl=14&itool=pubmed_docsum
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Dynamic color Doppler sonography of intestinal wall in patients with Crohn disease compared with healthy subjects. Author(s): Scholbach T, Herrero I, Scholbach J. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15572893&query_hl=14&itool=pubmed_docsum
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Early bronchopulmonary involvement in Crohn disease: a case report. Author(s): Valletta E, Bertini M, Sette L, Braggion C, Pradal U, Zannoni M. Source: Bmc Gastroenterology [electronic Resource]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11734067&query_hl=14&itool=pubmed_docsum
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Effect of growth hormone therapy in patients with Crohn disease. Author(s): Henker J. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11930104&query_hl=14&itool=pubmed_docsum
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Effectiveness of infliximab in the treatment of refractory perineal cutaneous Crohn disease. Author(s): Geyer AS, Anhalt GJ, Nousari HC. Source: Archives of Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10768643&query_hl=14&itool=pubmed_docsum
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Effects of serum from children with newly diagnosed Crohn disease on primary cultures of rat osteoblasts. Author(s): Varghese S, Wyzga N, Griffiths AM, Sylvester FA. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12454579&query_hl=14&itool=pubmed_docsum
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Efficacy of long-term treatment with thalidomide in children and young adults with Crohn disease: preliminary results. Author(s): Facchini S, Candusso M, Martelossi S, Liubich M, Panfili E, Ventura A. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11321389&query_hl=14&itool=pubmed_docsum
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Elevated diet-induced thermogenesis and lipid oxidation rate in Crohn disease. Author(s): Mingrone G, Capristo E, Greco AV, Benedetti G, De Gaetano A, Tataranni PA, Gasbarrini G. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9989699&query_hl=14&itool=pubmed_docsum
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Elevated plasma (1-->3)-beta-D-glucan, a fungal cell wall constituent, in a subgroup of Crohn disease. Author(s): Chiba M, Mikami K, Iizuka M, Yukawa M, Watanabe S, Takazoe M, Fukushima T, Koganei K, Kishibe T. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11336174&query_hl=14&itool=pubmed_docsum
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Enteral nutrition in Crohn disease: more than just calories. Author(s): Heuschkel R. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15076619&query_hl=14&itool=pubmed_docsum
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Enteroclysis findings of intestinal Behcet disease: a comparative study with Crohn disease. Author(s): Korman U, Cantasdemir M, Kurugoglu S, Mihmanli I, Soylu N, Hamuryudan V, Yazici H. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12719899&query_hl=14&itool=pubmed_docsum
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Enterovenous fistula: unusual complication of Crohn disease. Author(s): Ajzen SA, Gibney RG, Cooperberg PL, Scudamore CH, Miller RR. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3340772&query_hl=14&itool=pubmed_docsum
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Enterovesical fistulas in Crohn disease. Author(s): Badlani G, Sutton AP, Abrams HJ, Buchbinder M, Levin L. Source: Urology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7445307&query_hl=14&itool=pubmed_docsum
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Epidural gas: an unusual complication of Crohn disease. Author(s): Burke V, Mall JC. Source: Ajnr. American Journal of Neuroradiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6421117&query_hl=14&itool=pubmed_docsum
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Erythema elevatum diutinum and Crohn disease: a common pathogenic role for measles virus? Author(s): Orteu CH, McGregor JM, Whittaker SJ, Balzola F, Wakefield AJ. Source: Archives of Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8961895&query_hl=14&itool=pubmed_docsum
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Esophageal Crohn disease in children: a clinical spectrum. Author(s): Ramaswamy K, Jacobson K, Jevon G, Israel D. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12658034&query_hl=14&itool=pubmed_docsum
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Evaluation of Crohn disease activity with magnetic resonance imaging. Author(s): Maccioni F, Viscido A, Broglia L, Marrollo M, Masciangelo R, Caprilli R, Rossi P. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10823437&query_hl=14&itool=pubmed_docsum
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Evaluation of the pediatric Crohn disease activity index: a prospective multicenter experience. Author(s): Hyams J, Markowitz J, Otley A, Rosh J, Mack D, Bousvaros A, Kugathasan S, Pfefferkorn M, Tolia V, Evans J, Treem W, Wyllie R, Rothbaum R, del Rosario J, Katz A, Mezoff A, Oliva-Hemker M, Lerer T, Griffiths A; Pediatric Inflammatory Bowel Disease Collaborative Research Group. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16205508&query_hl=14&itool=pubmed_docsum
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Expressing the differences between Crohn disease and ulcerative colitis. Author(s): Wijmenga C. Source: Plos Med. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16120009&query_hl=14&itool=pubmed_docsum
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Expression of osteopontin (Eta-1) in Crohn disease of the terminal ileum. Author(s): Gassler N, Autschbach F, Gauer S, Bohn J, Sido B, Otto HF, Geiger H, Obermuller N. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12465727&query_hl=14&itool=pubmed_docsum
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Familial occurrence of Lesniowski--Crohn disease and ulcerative colitis. Author(s): Slotwinski R, Waluk R. Source: Acta Med Pol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=883516&query_hl=14&itool=pubmed_docsum
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Favorable response to infliximab treatment in a patient with active Crohn disease and pyoderma gangrenosum. Author(s): Triantafillidis JK, Cheracakis P, Sklavaina M, Apostolopoulou K. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12190104&query_hl=14&itool=pubmed_docsum
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Fecal diversion for Crohn disease of the colon. Author(s): Winslet MC, Keighley MR. Source: Surg Annu. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1858011&query_hl=14&itool=pubmed_docsum
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Fibrofatty proliferation of the mesentery in Crohn disease. Author(s): Herlinger H, Furth EE, Rubesin SE. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9663285&query_hl=14&itool=pubmed_docsum
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Findings at helical CT-enteroclysis in symptomatic patients with Crohn disease: correlation with endoscopic and surgical findings. Author(s): Turetschek K, Schober E, Wunderbaldinger P, Bernhard C, Schima W, Puespoek A, Vogelsang H, Moeschl P, Mostbeck G. Source: Journal of Computer Assisted Tomography. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12218807&query_hl=14&itool=pubmed_docsum
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Fine mapping of the IBD1 locus did not identify Crohn disease-associated NOD2 variants: implications for complex disease genetics. Author(s): van Heel DA, McGovern DP, Cardon LR, Dechairo BM, Lench NJ, Carey AH, Jewell DP. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12210321&query_hl=14&itool=pubmed_docsum
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Fournier gangrene associated with Crohn disease. Author(s): Jiang T, Covington JA, Haile CA, Murphy JB, Rotolo FS, Lake AM. Source: Mayo Clinic Proceedings. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10852429&query_hl=14&itool=pubmed_docsum
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Functional variants of OCTN cation transporter genes are associated with Crohn disease. Author(s): Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, Newman B, Van Oene M, Cescon D, Greenberg G, Griffiths AM, St George-Hyslop PH, Siminovitch KA. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15107849&query_hl=14&itool=pubmed_docsum
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Gallbladder motility in Crohn disease: influence of disease localization and bowel resection. Author(s): Vu MK, Gielkens HA, van Hogezand RA, van Oostayen JA, Lamers CB, Masclee AA. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11145286&query_hl=14&itool=pubmed_docsum
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Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases. Author(s): Fraquelli M, Losco A, Visentin S, Cesana BM, Pometta R, Colli A, Conte D. Source: Archives of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11575976&query_hl=14&itool=pubmed_docsum
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Gastric carcinoma in patients with Crohn disease: report of four cases. Author(s): Glick SN. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1853812&query_hl=14&itool=pubmed_docsum
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Gastritis associated with Crohn disease can be masked by Helicobacter pylori gastritis. Author(s): Herz R, Schaube J, Meining A, Stolte M. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10423061&query_hl=14&itool=pubmed_docsum
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Gastroduodenal Crohn disease. Author(s): Zagoren AJ. Source: Archives of Surgery (Chicago, Ill. : 1960). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=831667&query_hl=14&itool=pubmed_docsum
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Gastroduodenal Crohn disease. Author(s): Tootla F, Lucas RJ, Bernacki EG, Tabor H. Source: Archives of Surgery (Chicago, Ill. : 1960). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=942295&query_hl=14&itool=pubmed_docsum
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General case of the day. Enteropathic arthropathy secondary to Crohn disease. Author(s): Hill SC, Stutley JE, Conway WF. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7569122&query_hl=14&itool=pubmed_docsum
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Genetic evidence for interaction of the 5q31 cytokine locus and the CARD15 gene in Crohn disease. Author(s): Mirza MM, Fisher SA, King K, Cuthbert AP, Hampe J, Sanderson J, Mansfield J, Donaldson P, Macpherson AJ, Forbes A, Schreiber S, Lewis CM, Mathew CG. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12618963&query_hl=14&itool=pubmed_docsum
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Genetic testing in Crohn disease: utility in individualizing patient management. Author(s): Mascheretti S, Schreiber S. Source: American Journal of Pharmacogenomics : Genomics-Related Research in Drug Development and Clinical Practice. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16078858&query_hl=14&itool=pubmed_docsum
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Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Author(s): Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z, Delmonte T, Kocher K, Miller K, Guschwan S, Kulbokas EJ, O'Leary S, Winchester E, Dewar K, Green T, Stone V, Chow C, Cohen A, Langelier D, Lapointe G, Gaudet D, Faith J, Branco N, Bull SB, McLeod RS, Griffiths AM, Bitton A, Greenberg GR, Lander ES, Siminovitch KA, Hudson TJ. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11586304&query_hl=14&itool=pubmed_docsum
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Genetics of Crohn disease, an archetypal inflammatory barrier disease. Author(s): Schreiber S, Rosenstiel P, Albrecht M, Hampe J, Krawczak M. Source: Nature Reviews. Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15861209&query_hl=14&itool=pubmed_docsum
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Genital cutaneous Crohn disease: two cases with unusual clinical and histopathologic features in young men. Author(s): Acker SM, Sahn EE, Rogers HC, Maize JC, Moscatello SA, Frick KA. Source: The American Journal of Dermatopathology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11048982&query_hl=14&itool=pubmed_docsum
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Grafting the unhealed perineal wound after coloproctectomy for Crohn disease. Author(s): Anderson R, Turnbull RB Jr. Source: Archives of Surgery (Chicago, Ill. : 1960). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=176964&query_hl=14&itool=pubmed_docsum
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Granulomatosis cheilitis and Crohn disease. Author(s): Somech R, Harel A, Rotshtein MS, Brazowski E, Reif S. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11345191&query_hl=14&itool=pubmed_docsum
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Granulomatous pneumonitis, sclerosing cholangitis, and pancreatitis in a child with Crohn disease: response to infliximab. Author(s): Silbermintz A, Krishnan S, Banquet A, Markowitz J. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16540804&query_hl=14&itool=pubmed_docsum
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Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn disease. Author(s): Thayu M, Markowitz JE, Mamula P, Russo PA, Muinos WI, Baldassano RN. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15699701&query_hl=14&itool=pubmed_docsum
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High incidence of upper gastrointestinal tract involvement in children with Crohn disease. Author(s): Lenaerts C, Roy CC, Vaillancourt M, Weber AM, Morin CL, Seidman E. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2717294&query_hl=14&itool=pubmed_docsum
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High risk of infectious disease caused by salmonellae and mycobacteria infections in patients with Crohn disease treated with anti-interleukin-12 antibody. Author(s): Fieschi C, Allez M, Casanova JL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15825051&query_hl=14&itool=pubmed_docsum
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High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12. Author(s): Duerr RH, Barmada MM, Zhang L, Pfutzer R, Weeks DE. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10747815&query_hl=14&itool=pubmed_docsum
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High-dose immune suppression and autologous hematopoietic stem cell transplantation in refractory Crohn disease. Author(s): Burt RK, Traynor A, Oyama Y, Craig R. Source: Blood. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12393477&query_hl=14&itool=pubmed_docsum
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Higher proliferative capacity of T lymphocytes from patients with Crohn disease than from ulcerative colitis is disclosed by use of Herpesvirus saimiri-transformed T-cell lines. Author(s): Aguilera-Montilla N, Perez-Blas M, Valeri AP, Lopez-Santalla M, RodriguezJuan C, Mencia A, Castellano G, Manzano ML, Casis B, Sanchez F, Martin-Villa JM. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15743001&query_hl=14&itool=pubmed_docsum
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Highly destructive perianal Crohn disease. Author(s): Eradi B, Sandhu BK, Spray C, Cusick E. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16254528&query_hl=14&itool=pubmed_docsum
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How NOD-ing off leads to Crohn disease. Author(s): O'Neill LA. Source: Nature Immunology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15282558&query_hl=14&itool=pubmed_docsum
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Hyperthyroidism in two patients with Crohn disease and Takayasu arteritis. Author(s): Kettaneh A, Prevot S, Biaggi A, Stirnemann J, Fain O, Hocqueloux L, Mouas H, Levy VG, Thomas M. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12940446&query_hl=14&itool=pubmed_docsum
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Iatrogenic Trichuris suis infection in a patient with Crohn disease. Author(s): Kradin RL, Badizadegan K, Auluck P, Korzenik J, Lauwers GY. Source: Archives of Pathology & Laboratory Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16683891&query_hl=14&itool=pubmed_docsum
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IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis. Author(s): Giallourakis C, Stoll M, Miller K, Hampe J, Lander ES, Daly MJ, Schreiber S, Rioux JD. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12776251&query_hl=14&itool=pubmed_docsum
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IgA nephropathy and thin basement membrane disease in association with Crohn disease. Author(s): McCallum D, Smith L, Harley F, Yiu V. Source: Pediatric Nephrology (Berlin, Germany). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9323297&query_hl=14&itool=pubmed_docsum
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Improvement of Pyoderma gangrenosum and psoriasis associated with Crohn disease with anti-tumor necrosis factor alpha monoclonal antibody. Author(s): Tan MH, Gordon M, Lebwohl O, George J, Lebwohl MG. Source: Archives of Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11453813&query_hl=14&itool=pubmed_docsum
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In vitro release of eosinophil cationic protein from peripheral eosinophils reflects disease activity in childhood Crohn disease and ulcerative colitis. Author(s): Luck W, Becker M, Niggemann B, Wahn U. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9453373&query_hl=14&itool=pubmed_docsum
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Incidence of Crohn disease in the Czech Republic in the years 1990 to 2001 and assessment of pediatric population with inflammatory bowel disease. Author(s): Pozler O, Maly J, Bonova O, Dedek P, Fruhauf P, Havlickova A, Janatova T, Jimramovsky F, Klimova L, Klusacek D, Kocourkova D, Kolek A, Kotalova R, Marx D, Nevoral J, Petro R, Petru O, Plasilova I, Seidl Z, Sekyrova I, Semendak N, Schreierova I, Stanek J, Sykora J, Sulakova A, Toukalkova L, Travnickova R, Volf V, Zahradnicek L, Zeniskova I. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16456413&query_hl=14&itool=pubmed_docsum
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Increased expression of TCR vbeta5.1 and 8 in mucosal T-cell lines cultured from patients with Crohn disease. Author(s): Kelsen J, Agnholt J, Hoffmann HJ, Kaltoft K, Dahlerup JF. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15074393&query_hl=14&itool=pubmed_docsum
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Increased intestinal permeability in Crohn disease. Author(s): Grossman CM. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3826977&query_hl=14&itool=pubmed_docsum
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Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohn disease. Author(s): Nielsen HJ, Mortensen T, Holten-Andersen M, Brunner N, Sorensen S, RaskMadsen J. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11305513&query_hl=14&itool=pubmed_docsum
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Increased response of blood eosinophils to various chemotactic agents in quiescent Crohn disease. Author(s): Denis MA, Louis R, Malaise M, Belaiche J, Louis E. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11252412&query_hl=14&itool=pubmed_docsum
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Infantile Crohn disease presenting with diarrhea and pyoderma gangrenosum. Author(s): Dinulos JG, Darmstadt GL, Len MK, Rutledge JC, Murray KF. Source: Pediatric Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16445411&query_hl=14&itool=pubmed_docsum
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Infliximab as first-line therapy in severe pediatric Crohn disease. Author(s): de Ridder L, Benninga MA, Taminiau JA, Hommes DW. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16954965&query_hl=14&itool=pubmed_docsum
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Infliximab therapy in 30 patients with refractory pediatric Crohn disease with and without fistulas in The Netherlands. Author(s): de Ridder L, Escher JC, Bouquet J, Schweizer JJ, Rings EH, Tolboom JJ, Houwen RH, Norbruis OF, Derkx BH, Taminiau JA. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15187780&query_hl=14&itool=pubmed_docsum
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Infliximab treatment of Crohn disease ileovesical fistula. Author(s): Game X, Malavaud B, Alric L, Mouzin M, Sarramon JP, Rischmann P. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14621288&query_hl=14&itool=pubmed_docsum
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Interaction of polymorphisms in the CARD15 and CD14 genes in patients with Crohn disease. Author(s): Klein W, Tromm A, Griga T, Folwaczny C, Hocke M, Eitner K, Marx M, Duerig N, Epplen JT. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12940436&query_hl=14&itool=pubmed_docsum
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Interleukin-10 expression in intestine of Crohn disease. Author(s): Akagi S, Hiyama E, Imamura Y, Takesue Y, Matsuura Y, Yokoyama T. Source: International Journal of Molecular Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10719056&query_hl=14&itool=pubmed_docsum
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International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn disease and chromosome 16. Author(s): Cavanaugh J; IBD International Genetics Consortium. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11309682&query_hl=14&itool=pubmed_docsum
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Intracranial sinus thrombosis in a patient with Crohn disease and factor V Leiden mutation. Author(s): Maag J, Prayson RA. Source: Archives of Pathology & Laboratory Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12873183&query_hl=14&itool=pubmed_docsum
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Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial. Author(s): Gasche C, Dejaco C, Waldhoer T, Tillinger W, Reinisch W, Fueger GF, Gangl A, Lochs H. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9148651&query_hl=14&itool=pubmed_docsum
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Inverted Meckel's diverticulum masquerading Crohn disease in the small intestine. Author(s): Henneberg Holmboe C, Thorlacius-Ussing O, Teglbjaerg PS, Vinter-Jensen L. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12678342&query_hl=14&itool=pubmed_docsum
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Involvement of Meckel diverticulum in Crohn disease associated with pancreatic heterotopia. Author(s): Mourra N, Tiret E, Caplin S, Gendre JP, Parc R, Flejou JF. Source: Archives of Pathology & Laboratory Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12562264&query_hl=14&itool=pubmed_docsum
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Isolated cerebral thrombo-embolism and Crohn disease. Author(s): Gormally SM, Bourke W, Kierse B, Monaghan H, McMenamin J, Drumm B. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8529679&query_hl=14&itool=pubmed_docsum
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Jumping translocations involving chromosome 1q in a patient with Crohn disease and acute monocytic leukemia: a review of the literature on jumping translocations in hematological malignancies and Crohn disease. Author(s): Reddy KS, Parsons L, Colman L. Source: Cancer Genetics and Cytogenetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10087950&query_hl=14&itool=pubmed_docsum
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Juvenile myelomonocytic leukemia in a child with Crohn disease. Author(s): Oliver JW, Farnsworth B, Tonk VS. Source: Cancer Genetics and Cytogenetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16682290&query_hl=14&itool=pubmed_docsum
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Knee pain and swelling due to Crohn disease. A case report. Author(s): Olszewski MA, Manos RE, Weis PJ, Provencher MT. Source: The Journal of Bone and Joint Surgery. American Volume. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16085629&query_hl=14&itool=pubmed_docsum
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Laparoscopic vs conventional ileocolectomy for primary Crohn disease. Author(s): Shore G, Gonzalez QH, Bondora A, Vickers SM. Source: Archives of Surgery (Chicago, Ill. : 1960). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12511156&query_hl=14&itool=pubmed_docsum
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Laparoscopic-assisted versus open ileocolic resection for adolescent Crohn disease. Author(s): Diamond IR, Langer JC. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11740226&query_hl=14&itool=pubmed_docsum
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Laparoscopy for Crohn disease. Author(s): Zmora O. Source: Semin Laparosc Surg. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14760463&query_hl=14&itool=pubmed_docsum
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Left hydronephrosis caused by Crohn disease successfully treated conservatively. Author(s): Ben-Ami H, Lavy A, Behar DM, Ginesin Y, Fischer D, Edoute Y. Source: The American Journal of the Medical Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11061356&query_hl=14&itool=pubmed_docsum
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Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease. G.E.T.A.I.D. Author(s): Hugot JP, Laurent-Puig P, Gower-Rousseau C, Caillat-Zucman S, Beaugerie L, Dupas JL, Van Gossum A, Bonait-Pellie C, Cortot A, Thomas G. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7802010&query_hl=14&itool=pubmed_docsum
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Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease. Author(s): Wendland BE, Aghdassi E, Tam C, Carrrier J, Steinhart AH, Wolman SL, Baron D, Allard JP. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11470730&query_hl=14&itool=pubmed_docsum
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Long-term endoscopic remission of Crohn disease after autologous stem cell transplantation for acute myeloid leukaemia. Author(s): Soderholm JD, Malm C, Juliusson G, Sjodahl R. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12059066&query_hl=14&itool=pubmed_docsum
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Long-term outcome of total colectomy and ileostomy for Crohn disease. Author(s): Yamamoto T, Keighley MR. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10232873&query_hl=14&itool=pubmed_docsum
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Low blood selenium concentration in Crohn disease. Author(s): Loeschke K, Konig A, Trebert Haeberlin S, Lux F. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3579076&query_hl=14&itool=pubmed_docsum
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Lung infection due to opportunistic fungus, Phialemonium obovatum, in a bone marrow transplant recipient: an emerging infection with fungemia and Crohn disease-like involvement of the gastrointestinal tract. Author(s): Scott RS, Sutton DA, Jagirdar J. Source: Annals of Diagnostic Pathology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16084458&query_hl=14&itool=pubmed_docsum
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Magnetic resonance imaging of Crohn disease: early recognition of treatment response and relapse. Author(s): Madsen SM, Thomsen HS, Munkholm P, Schlichting P, Davidsen B. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9013526&query_hl=14&itool=pubmed_docsum
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Manifestations of Crohn disease at US. Author(s): Sarrazin J, Wilson SR. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8897619&query_hl=14&itool=pubmed_docsum
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Mast cells and eosinophils have a potential profibrogenic role in Crohn disease. Author(s): Xu X, Rivkind A, Pikarsky A, Pappo O, Bischoff SC, Levi-Schaffer F. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15180181&query_hl=14&itool=pubmed_docsum
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Medical risk factors for small-bowel adenocarcinoma with focus on Crohn disease: a European population-based case-control study. Author(s): Kaerlev L, Teglbjaerg PS, Sabroe S, Kolstad HA, Ahrens W, Eriksson M, Guenel P, Hardell L, Launoy G, Merler E, Merletti F, Stang A. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11424324&query_hl=14&itool=pubmed_docsum
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Mesenteric border linear ulcer in Crohn disease: historical, radiologic, and pathologic perspectives. Author(s): Herlinger H, Rubesin SE, Furth EE. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9516496&query_hl=14&itool=pubmed_docsum
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Metastatic Crohn disease of the vulva. Author(s): Levine EM, Barton JJ, Grier EA. Source: Obstetrics and Gynecology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7121922&query_hl=14&itool=pubmed_docsum
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Methotrexate-induced esophagitis in a child with Crohn disease. Author(s): Batres LA, Gabriel CA, Tsou VM. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14508226&query_hl=14&itool=pubmed_docsum
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Miliary tuberculosis following infliximab therapy for Crohn disease: A case report and review of the literature. Author(s): Stas P, D'Hoore A, Van Assche G, Geboes K, Steenkiste E, Penninckx F, Rutgeerts P, Vermeire S. Source: Acta Gastroenterol Belg. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16929619&query_hl=14&itool=pubmed_docsum
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Mitochondrial dysfunction in a patient with Crohn disease: possible role in pathogenesis. Author(s): Restivo NL, Srivastava MD, Schafer IA, Hoppel CL. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15097444&query_hl=14&itool=pubmed_docsum
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Molecular evidence for two forms of Crohn disease. Author(s): Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ. Source: Proceedings of the National Academy of Sciences of the United States of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7809109&query_hl=14&itool=pubmed_docsum
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More questions about growth hormone in Crohn disease. Author(s): Stricker T, Braegger CP. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11601435&query_hl=14&itool=pubmed_docsum
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MR enteroclysis imaging of Crohn disease. Author(s): Prassopoulos P, Papanikolaou N, Grammatikakis J, Rousomoustakaki M, Maris T, Gourtsoyiannis N. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11598255&query_hl=14&itool=pubmed_docsum
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MR imaging in patients with Crohn disease: value of T2- versus T1-weighted gadolinium-enhanced MR sequences with use of an oral superparamagnetic contrast agent. Author(s): Maccioni F, Bruni A, Viscido A, Colaiacomo MC, Cocco A, Montesani C, Caprilli R, Marini M. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16371574&query_hl=14&itool=pubmed_docsum
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MR imaging of anorectal Crohn disease: a pictorial essay. Author(s): O'Donovan AN, Somers S, Farrow R, Mernagh JR, Sridhar S. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9017802&query_hl=14&itool=pubmed_docsum
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MR imaging of Crohn disease: use of perflubron as a gastrointestinal contrast agent. Author(s): Anderson CM, Brown JJ, Balfe DM, Heiken JP, Borrello JA, Clouse RE, Pilgram TK. Source: Journal of Magnetic Resonance Imaging : Jmri. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8061454&query_hl=14&itool=pubmed_docsum
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MRI evaluation of Crohn disease activity. Author(s): Lichtenstein GR, Schnall M, Herlinger H. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10823438&query_hl=14&itool=pubmed_docsum
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Mutation, selection, and evolution of the Crohn disease susceptibility gene CARD15. Author(s): King K, Sheikh MF, Cuthbert AP, Fisher SA, Onnie CM, Mirza MM, Pattni RC, Sanderson J, Forbes A, Mansfield J, Lewis CM, Roberts RG, Mathew CG. Source: Human Mutation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16278823&query_hl=14&itool=pubmed_docsum
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Myelodysplastic syndrome, pyoderma gangrenosum, and Crohn disease. Author(s): Sandoval C. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11846312&query_hl=14&itool=pubmed_docsum
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Neovascular glaucoma as a complication of retinal vasculitis in Crohn disease. Author(s): Salmon JF, Ursell PG, Frith P. Source: American Journal of Ophthalmology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11024432&query_hl=14&itool=pubmed_docsum
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Newly diagnosed chronic granulomatous disease in a 53-year-old woman with Crohn disease. Author(s): Ramanuja S, Wolf KM, Sadat MA, Mahoney SJ, Dinauer MC, Nelson RP Jr. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16136772&query_hl=14&itool=pubmed_docsum
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Nipple valve anastomosis for preventing recurrence of Crohn disease in the neoterminal ileum after ileocolic resection. A prospective pilot study. Author(s): Bakkevold KE. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10766324&query_hl=14&itool=pubmed_docsum
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Nonspecific involvement of bowel adjoining Crohn disease. Author(s): Herlinger H, O'Riordan D, Saul S, Levine MS. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3952329&query_hl=14&itool=pubmed_docsum
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Novel therapies for Crohn disease and colitis. Author(s): Saibil F. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9068567&query_hl=14&itool=pubmed_docsum
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Nutritional status and energy metabolism in Crohn disease. Author(s): Capristo E, Addolorato G, Mingrone G, Greco AV, Gasbarrini G. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9989702&query_hl=14&itool=pubmed_docsum
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Obliterative muscularization of the small bowel submucosa in Crohn disease: a possible mechanism of small bowel obstruction. Author(s): Koukoulis G, Ke Y, Henley JD, Cummings OW. Source: Archives of Pathology & Laboratory Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11570909&query_hl=14&itool=pubmed_docsum
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On the etiology of Crohn disease. Author(s): Mishina D, Katsel P, Brown ST, Gilberts EC, Greenstein RJ. Source: Proceedings of the National Academy of Sciences of the United States of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8790414&query_hl=14&itool=pubmed_docsum
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Oral budesonide significantly improves water absorption in patients with ileostomy for Crohn disease. Author(s): Ecker KW, Stallmach A, Seitz G, Gierend M, Greinwald R, Achenbach U. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12737444&query_hl=14&itool=pubmed_docsum
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Oral Crohn disease: clinical characteristics and long-term follow-up of 9 cases. Author(s): Dupuy A, Cosnes J, Revuz J, Delchier JC, Gendre JP, Cosnes A. Source: Archives of Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10206051&query_hl=14&itool=pubmed_docsum
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Oral manifestations of Crohn disease: update of the literature and report of case. Author(s): Boraz RA. Source: Asdc J Dent Child. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3276750&query_hl=14&itool=pubmed_docsum
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Orbital pseudotumor and Crohn disease. Author(s): Camfield PR, White M, Warner HA, Lythgoe C. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7086617&query_hl=14&itool=pubmed_docsum
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Orbital pseudotumor and Crohn disease. Author(s): Young RS, Hodes BL, Cruse RP, Koch KL, Garovoy MR. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7252686&query_hl=14&itool=pubmed_docsum
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Orocaecal transit time in patients with Crohn disease. Author(s): Gotze H, Ptok A. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8444243&query_hl=14&itool=pubmed_docsum
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Paraparesis in a patient with Crohn disease resulting from septic arthritis of the hip and psoas abscess. Author(s): Femminineo AF, LaBan MM. Source: Archives of Physical Medicine and Rehabilitation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3348726&query_hl=14&itool=pubmed_docsum
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Pediatric Crohn Disease Activity Index: responsive to short-term change. Author(s): Kundhal PS, Critch JN, Zachos M, Otley AR, Stephens D, Griffiths AM. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12500001&query_hl=14&itool=pubmed_docsum
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Percutaneous abscess drainage in Crohn disease: technical success and short- and long-term outcomes during 14 years. Author(s): Gervais DA, Hahn PF, O'Neill MJ, Mueller PR. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11867780&query_hl=14&itool=pubmed_docsum
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Percutaneous drainage of abscesses in patients with Crohn disease. Author(s): Lambiase RE, Cronan JJ, Dorfman GS, Paolella LP, Haas RA. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3258704&query_hl=14&itool=pubmed_docsum
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Percutaneous drainage of abscesses in patients with Crohn disease. Author(s): Leder RA, Dunnick NR. Source: Investigative Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2745014&query_hl=14&itool=pubmed_docsum
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Percutaneous management of multiple bilateral liver abscesses complicating Crohn disease. Author(s): Goletti O, Angrisano C, Lippolis PV, Zocco G, Galatioto C, Lorenzetti L, Musco B, Armillotta N, Cavina E. Source: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11330380&query_hl=14&itool=pubmed_docsum
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Perianal complications of Crohn disease: MR imaging findings. Author(s): Laniado M, Makowiec F, Dammann F, Jehle EC, Claussen CD, Starlinger M. Source: European Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9265670&query_hl=14&itool=pubmed_docsum
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Perianal Crohn disease: a new scoring system to evaluate and predict outcome of surgical intervention. Author(s): Pikarsky AJ, Gervaz P, Wexner SD. Source: Archives of Surgery (Chicago, Ill. : 1960). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12093328&query_hl=14&itool=pubmed_docsum
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Perianal Crohn disease: predictors of need for permanent diversion. Author(s): Galandiuk S, Kimberling J, Al-Mishlab TG, Stromberg AJ. Source: Annals of Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15849515&query_hl=14&itool=pubmed_docsum
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Photopheresis treatment in severe Crohn disease. Author(s): Guariso G, D'Inca R, Sturniolo GC, Zancan L, Dall'Amico R. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14508227&query_hl=14&itool=pubmed_docsum
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Pilot feasibility studies of leukocytapheresis with the Adacolumn Apheresis System in patients with active ulcerative colitis or Crohn disease. Author(s): Sands BE, Sandborn WJ, Wolf DC, Katz S, Safdi M, Schwartz DA, Hanauer SB. Source: Journal of Clinical Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16825929&query_hl=14&itool=pubmed_docsum
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Polymorphism of heat-shock protein gene HSP70-2 in Crohn disease: possible genetic marker for two forms of Crohn disease. Author(s): Esaki M, Furuse M, Matsumoto T, Aoyagi K, Jo Y, Yamagata H, Nakano H, Fujishima M. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10466882&query_hl=14&itool=pubmed_docsum
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Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis. Author(s): Potocnik U, Ferkolj I, Glavac D, Dean M. Source: Genes and Immunity. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15505619&query_hl=14&itool=pubmed_docsum
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Portal pyaemia as a presenting feature of paediatric Crohn disease. Author(s): El-Matary W, Jaffray B, Scott J, Hodges S. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16877996&query_hl=14&itool=pubmed_docsum
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Possible activation of an intramyocardial inflammatory process ( Staphylococcus aureus)after treatment with infliximab in a boy with Crohn disease. Author(s): Reichardt P, Dahnert I, Tiller G, Hausler HJ. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12012225&query_hl=14&itool=pubmed_docsum
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Predictive value of small bowel radiography for recurrent Crohn Disease. Author(s): Ekberg O, Fork FT, Hildell J. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6778146&query_hl=14&itool=pubmed_docsum
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Prevalence of mutations of the NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn disease. Author(s): Mendoza JL, Murillo LS, Fernandez L, Pena AS, Lana R, Urcelay E, CruzSantamaria DM, de la Concha EG, Diaz-Rubio M, Garcia-Paredes J. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14750643&query_hl=14&itool=pubmed_docsum
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Preventive effect of nutritional therapy against postoperative recurrence of Crohn disease, with reference to findings determined by intra-operative enteroscopy. Author(s): Esaki M, Matsumoto T, Hizawa K, Nakamura S, Jo Y, Mibu R, Iida M. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16316891&query_hl=14&itool=pubmed_docsum
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Primary Hodgkin disease of the ileum complicating Crohn disease. Author(s): Vanbockrijck M, Cabooter M, Casselman J, Vanvuchelen J, Van Hoof A, Michielssen P. Source: Cancer. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8348509&query_hl=14&itool=pubmed_docsum
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Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. Author(s): Visekruna A, Joeris T, Seidel D, Kroesen A, Loddenkemper C, Zeitz M, Kaufmann SH, Schmidt-Ullrich R, Steinhoff U. Source: The Journal of Clinical Investigation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17124531&query_hl=14&itool=pubmed_docsum
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Pseudo-ileovesical fistula in Crohn disease. Author(s): Panitch NM, Henn RM, Tetrud JW. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1173172&query_hl=14&itool=pubmed_docsum
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Pyoderma gangrenosum associated with Crohn disease: effect of TNF-alpha blockade with infliximab. Author(s): Ljung T, Staun M, Grove O, Fausa O, Vatn MH, Hellstrom PM. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12374238&query_hl=14&itool=pubmed_docsum
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Quality of life study in a regional group of patients with Crohn disease. A structured interview study. Author(s): Guassora AD, Kruuse C, Thomsen OO, Binder V. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11099060&query_hl=14&itool=pubmed_docsum
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Radiologic appearance of recurrent ileal Crohn disease. Author(s): Zalev AH, Deitel W, Kundu S, Tomlinson G. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16252144&query_hl=14&itool=pubmed_docsum
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Radiologic diagnosis of Crohn disease (with emphasis on its early manifestations). Author(s): Kelvin FM, Gedgaudas RK. Source: Critical Reviews in Diagnostic Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7023841&query_hl=14&itool=pubmed_docsum
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RDP58, a novel immunomodulatory peptide with anti-inflammatory effects. A pharmacological study in trinitrobenzene sulphonic acid colitis and Crohn disease. Author(s): Bourreille A, Doubremelle M, de la Bletiere DR, Segain JP, Toquet C, Buelow R, Galmiche JP. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12795464&query_hl=14&itool=pubmed_docsum
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Recanalization of the superior mesenteric vein for massive bleeding in Crohn disease. Author(s): Martin EC, Laffey KJ, Bixon R. Source: Journal of Vascular and Interventional Radiology : Jvir. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8541671&query_hl=14&itool=pubmed_docsum
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Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease. Author(s): Mantyh CR, Gates TS, Zimmerman RP, Welton ML, Passaro EP Jr, Vigna SR, Maggio JE, Kruger L, Mantyh PW. Source: Proceedings of the National Academy of Sciences of the United States of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2834738&query_hl=14&itool=pubmed_docsum
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Recognition of Crohn disease on incidental gastric biopsy in childhood. Author(s): Pascasio JM, Hammond S, Qualman SJ. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12658540&query_hl=14&itool=pubmed_docsum
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Rectal nitric oxide assessment in children with Crohn disease and ulcerative colitis. Indicator of ileocaecal and colorectal affection. Author(s): Ljung T, Herulf M, Beijer E, Jacobsson H, Lundberg J, Finkel Y, Hellstrom PM. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11589381&query_hl=14&itool=pubmed_docsum
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Rectourethrocutaneous fistula in Crohn disease. Author(s): Stein EJ, Banner MP, Pollack HM. Source: Urol Radiol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6612911&query_hl=14&itool=pubmed_docsum
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Relative sensitivity of Tc-99m WBC versus In-111 WBC in a patient with Crohn disease and steroid use. Author(s): Challa S, Lyons KP, Broekelschen P, Milne N. Source: Clinical Nuclear Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9343728&query_hl=14&itool=pubmed_docsum
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Remediable defects in Crohn disease: a prospective study of 63 patients. Author(s): Beeken WL. Source: Archives of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1052664&query_hl=14&itool=pubmed_docsum
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Renal artery stenosis associated with Crohn disease. Author(s): Kuzmic AC, Kolacek S, Brkljacic B, Huzjak N. Source: Pediatric Nephrology (Berlin, Germany). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11354784&query_hl=14&itool=pubmed_docsum
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Resolution of severe peristomal pyoderma gangrenosum with infliximab in a child with Crohn disease. Author(s): Batres LA, Mamula P, Baldassano RN. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12050585&query_hl=14&itool=pubmed_docsum
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Retrobulbar optic neuritis associated with infliximab in a patient with Crohn disease. Author(s): Strong BY, Erny BC, Herzenberg H, Razzeca KJ. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15096366&query_hl=14&itool=pubmed_docsum
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Role of the CARD15 gene in the pathogenesis of Crohn disease: phenotypic classification and prognostic implications. Author(s): Murillo LS, Morre SA, Pena AS. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14686713&query_hl=14&itool=pubmed_docsum
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Role of US in detection of Crohn disease: meta-analysis. Author(s): Fraquelli M, Colli A, Casazza G, Paggi S, Colucci A, Massironi S, Duca P, Conte D. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15987966&query_hl=14&itool=pubmed_docsum
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Salvage after anastomotic leak in Crohn disease. Utilization of a new, simple diverting ileostomy. Author(s): Handelsman JC, Fishbein RH, Bayless T, Burbige E. Source: Archives of Surgery (Chicago, Ill. : 1960). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=949251&query_hl=14&itool=pubmed_docsum
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Science to practice: do mural attenuation and thickness at contrast-enhanced CT enterography correlate with endoscopic and histologic findings of inflammation in Crohn disease? Author(s): Maglinte DD. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16436802&query_hl=14&itool=pubmed_docsum
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Screening for dysplasia and TP53 mutations in closed rectal stumps of patients with ulcerative colitis or Crohn disease. Author(s): Winther KV, Bruun E, Federspiel B, Guldberg P, Binder V, Brynskov J. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15074392&query_hl=14&itool=pubmed_docsum
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Severe pancytopenia from thiopurine methyltransferase deficiency: a preventable complication of 6-mercaptopurine therapy in children with Crohn disease. Author(s): Rosen R, Integlia MJ, Bousvaros A. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12454589&query_hl=14&itool=pubmed_docsum
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Severe penile edema: an unusual presentation of metastatic Crohn disease. Author(s): Zelhof B, Biyani CS, Anathhanam AJ, Pollock B, Browning AJ. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16563150&query_hl=14&itool=pubmed_docsum
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Simple mucosal biopsy criteria differentiating among Crohn disease, ulcerative colitis, and other forms of colitis: measurement of validity. Author(s): Tanaka M, Saito H, Fukuda S, Sasaki Y, Munakata A, Kudo H. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10766322&query_hl=14&itool=pubmed_docsum
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Small bowel adenocarcinoma in Crohn disease patient complicated by microangiopathic hemolytic anemia. Author(s): Gusakova I, Mermershtain W, Cohen Y, Ariad S. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14528075&query_hl=14&itool=pubmed_docsum
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Small bowel Crohn disease: sonographic features. Author(s): Di Mizio R, Maconi G, Romano S, D'Amario F, Bianchi Porro G, Grassi R. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15160749&query_hl=14&itool=pubmed_docsum
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Small bowel obstruction secondary to Crohn disease: CT findings. Author(s): Zissin R, Hertz M, Paran H, Bernheim J, Shapiro-Feinberg M, Gayer G. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15354340&query_hl=14&itool=pubmed_docsum
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Sonographic detection of longitudinal ulcers in Crohn disease. Author(s): Kunihiro K, Hata J, Haruma K, Manabe N, Tanaka S, Chayama K. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15125463&query_hl=14&itool=pubmed_docsum
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Sonographic detection of postsurgical recurrence of Crohn disease. Author(s): DiCandio G, Mosca F, Campatelli A, Bianchini M, D'Elia F, Dellagiovampaola C. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3511636&query_hl=14&itool=pubmed_docsum
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Spiral CT demonstration of hypervascularity in Crohn disease: "vascular jejunization of the ileum" or the "comb sign". Author(s): Meyers MA, McGuire PV. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7549737&query_hl=14&itool=pubmed_docsum
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Spiral CT findings in active and remission phases in patients with Crohn disease. Author(s): Del Campo L, Arribas I, Valbuena M, Mate J, Moreno-Otero R. Source: Journal of Computer Assisted Tomography. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11584242&query_hl=14&itool=pubmed_docsum
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Splenic granulomas in Crohn disease. Author(s): Puli SR, Presti ME, Alpert MA. Source: The American Journal of the Medical Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14501230&query_hl=14&itool=pubmed_docsum
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Spontaneous free perforation of the ileum in Crohn disease: CT demonstration. Author(s): Goodman P, Raval B, Potter GD. Source: Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2598157&query_hl=14&itool=pubmed_docsum
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Spotlight on infliximab in Crohn disease and rheumatoid arthritis. Author(s): Siddiqui MA, Scott LJ. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16573354&query_hl=14&itool=pubmed_docsum
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Stapled functional end-to-end anastomosis versus sutured end-to-end anastomosis after ileocolonic resection in Crohn disease. Author(s): Yamamoto T, Bain IM, Mylonakis E, Allan RN, Keighley MR. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10466883&query_hl=14&itool=pubmed_docsum
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Steroid diabetes in children with Crohn disease. Author(s): Banac S, Persic M, Cvijovic K. Source: Acta Med Croatica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12455453&query_hl=14&itool=pubmed_docsum
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Stridor in Crohn disease and the use of infliximab. Author(s): Kirkcaldy J, Lim WS, Jones A, Pointon K. Source: Chest. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16899863&query_hl=14&itool=pubmed_docsum
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Subnormal alanine aminotransferase values in blood of patients with Crohn disease. Author(s): Vadstrup S. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15223680&query_hl=14&itool=pubmed_docsum
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Successful treatment of metastatic Crohn disease with infliximab. Author(s): Escher JC, Stoof TJ, van Deventer SJ, van Furth AM. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11930102&query_hl=14&itool=pubmed_docsum
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Sulphasalazine and prednisone compared with sulphasalazine for treating active Crohn disease. A double-blind, randomized, multicenter trial. Author(s): Rijk MC, van Hogezand RA, van Lier HJ, van Tongeren JH. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1671631&query_hl=14&itool=pubmed_docsum
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Surgical treatment of Crohn disease in children and adolescents; how conservative can the paediatrician be? Author(s): Aronson DC, Van Coevorden F, Heijmans HS, Gooszen HG. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8223801&query_hl=14&itool=pubmed_docsum
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Symptomatic exacerbation of Crohn disease after treatment with high-dose interleukin-2. Author(s): Sparano JA, Brandt LJ, Dutcher JP, DuBois JS, Atkins MB. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8452327&query_hl=14&itool=pubmed_docsum
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Systemic absorption with complications during topical tacrolimus treatment for orofacial Crohn disease. Author(s): Russell RK, Richardson N, Wilson DC. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11321395&query_hl=14&itool=pubmed_docsum
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Targeted drug delivery for refractory hemorrhagic Crohn disease. Author(s): Sze DY. Source: Journal of Vascular and Interventional Radiology : Jvir. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16415147&query_hl=14&itool=pubmed_docsum
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Tc-99m HMPAO-labeled leukocyte scintigraphy with hybrid SPECT/CT detects perianal fistulas in Crohn disease. Author(s): Filippi L, Biancone L, Petruzziello C, Schillaci O. Source: Clinical Nuclear Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16921278&query_hl=14&itool=pubmed_docsum
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T-cell receptors in ileal mucosal biopsies of patients with Crohn disease and spondylarthropathy. Author(s): Cuvelier C, de Wever N, Mielants H, De Vos M, Veys E, Roels H. Source: Progress in Histochemistry and Cytochemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1484962&query_hl=14&itool=pubmed_docsum
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Teaching self-administration of nasogastric tube insertion to an adolescent with Crohn disease. Author(s): Reimers TM, Vance MD, Young RJ. Source: J Appl Behav Anal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7601807&query_hl=14&itool=pubmed_docsum
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Thalidomide in Crohn disease and the risk of peripheral neuropathy. Author(s): Ahmed M, El-Hadi S, Jenkins HR. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14508228&query_hl=14&itool=pubmed_docsum
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Thalidomide in Crohn disease. Author(s): Pigott A, Casson D. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15699709&query_hl=14&itool=pubmed_docsum
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The association between the myelodysplastic syndromes and Crohn disease. Author(s): Eng C, Farraye FA, Shulman LN, Peppercorn MA, Krauss CM, Connors JM, Stone RM. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1530197&query_hl=14&itool=pubmed_docsum
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The CARD15 gene mutation in Crohn disease. Author(s): Vatn MH. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14686712&query_hl=14&itool=pubmed_docsum
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The effect of disease, drug, and diet on whole body protein metabolism in adolescents with Crohn disease and growth failure. Author(s): Motil KJ, Grand RJ, Maletskos CJ, Young VR. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6809923&query_hl=14&itool=pubmed_docsum
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The genetics of Crohn disease: complex segregation analysis of a family study with 265 patients with Crohn disease and 5,387 relatives. Author(s): Kuster W, Pascoe L, Purrmann J, Funk S, Majewski F. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2705471&query_hl=14&itool=pubmed_docsum
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The role of computed tomography in management of patients with Crohn disease. Author(s): Nanakawa S, Takahashi M, Takagi K, Takano M. Source: Clinical Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8364792&query_hl=14&itool=pubmed_docsum
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The role of microbes in Crohn's disease. Author(s): Eckburg PB, Relman DA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17173227&query_hl=16&itool=pubmed_docsum
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The value of routinely performed ultrasonography in patients with Crohn disease. Author(s): Hirche TO, Russler J, Schroder O, Schuessler G, Kappeser P, Caspary WF, Dietrich CF. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12408523&query_hl=14&itool=pubmed_docsum
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Therapeutic strategies for pediatric Crohn disease. Author(s): Grand RJ, Ramakrishna J, Calenda KA. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8889277&query_hl=14&itool=pubmed_docsum
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Therapy with recombinant growth hormone in children with Crohn disease and growth failure. Author(s): Henker J. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8956950&query_hl=14&itool=pubmed_docsum
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Toxic dilatation in Crohn disease with CT correlation. Author(s): Siskind BN, Burrell MI, Klein ML, Princenthal RA. Source: Journal of Computer Assisted Tomography. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3968266&query_hl=14&itool=pubmed_docsum
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Transient intussusception in Crohn disease: CT evaluation. Author(s): Knowles MC, Fishman EK, Kuhlman JE, Bayless TM. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2916035&query_hl=14&itool=pubmed_docsum
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Treatment of metastatic Crohn disease. Author(s): Sierra C, Barco A, del Rio L. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12454594&query_hl=14&itool=pubmed_docsum
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Trisomy 9 syndrome: report of a case with Crohn disease and review of the literature. Author(s): Wooldridge J, Zunich J. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7778585&query_hl=14&itool=pubmed_docsum
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Tumour necrosis factor alpha antibody affects gastrin release in Crohn disease. Author(s): Hopman WP, de Jong DJ, Naber AH, Jansen JB. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12795463&query_hl=14&itool=pubmed_docsum
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Ulcerative colitis and Crohn disease in children. Author(s): Motil KJ, Grand RJ. Source: Pediatrics in Review / American Academy of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3332367&query_hl=14&itool=pubmed_docsum
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Ultrasound examination of the small bowel: comparison with enteroclysis in patients with Crohn disease. Author(s): Solvig J, Ekberg O, Lindgren S, Floren CH, Nilsson P. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7549736&query_hl=14&itool=pubmed_docsum
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Ultrasound in the diagnosis of Crohn disease in childhood. Author(s): Caiulo VA, Latini G, De Felice C. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12647208&query_hl=14&itool=pubmed_docsum
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Upper gastrointestinal mucosal disease in pediatric Crohn disease and ulcerative colitis: a blinded, controlled study. Author(s): Tobin JM, Sinha B, Ramani P, Saleh AR, Murphy MS. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11396811&query_hl=14&itool=pubmed_docsum
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Use of quantitative ultrasound to assess osteopenia in children with Crohn disease. Author(s): Levine A, Mishna L, Ballin A, Givoni S, Dinari G, Hartman C, Shamir R. Source: Journal of Pediatric Gastroenterology and Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12187292&query_hl=14&itool=pubmed_docsum
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Viral etiology of Crohn disease. Author(s): Danilevicius Z. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=989818&query_hl=14&itool=pubmed_docsum
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Virus serology in familial Crohn disease. Author(s): Van Kruiningen HJ, Mayo DR, Vanopdenbosch E, Gower-Rousseau C, Cortot A, Colombel JF. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10831264&query_hl=14&itool=pubmed_docsum
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Vitamin D status in children, adolescents, and young adults with Crohn disease. Author(s): Sentongo TA, Semaeo EJ, Stettler N, Piccoli DA, Stallings VA, Zemel BS. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12399281&query_hl=14&itool=pubmed_docsum
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What role, if any, for laparoscopic surgery in Crohn disease of the hindgut? Author(s): Bergamaschi R. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11444464&query_hl=14&itool=pubmed_docsum
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Whole body BMC in pediatric Crohn disease: independent effects of altered growth, maturation, and body composition. Author(s): Burnham JM, Shults J, Semeao E, Foster B, Zemel BS, Stallings VA, Leonard MB. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15537438&query_hl=14&itool=pubmed_docsum
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Williams syndrome associated with Crohn disease, multiple infections, and chronic granulomatous disease. Author(s): Gilbert-Barness E, Fox T, Morrow G, Luquette M, Pomerance HH. Source: Fetal Pediatr Pathol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15371121&query_hl=14&itool=pubmed_docsum
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CHAPTER 2. ALTERNATIVE MEDICINE AND CROHN DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Crohn 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 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 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 disease: •
A new method for targeted drug delivery using polymeric microcapsules: implications for treatment of Crohn's disease. Author(s): Metz T, Jones ML, Chen H, Halim T, Mirzaei M, Haque T, Amre D, Das SK, Prakash S. Source: Cell Biochemistry and Biophysics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16043885&query_hl=1&itool=pubmed_docsum
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A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn's disease. Author(s): Bousvaros A, Guandalini S, Baldassano RN, Botelho C, Evans J, Ferry GD, Goldin B, Hartigan L, Kugathasan S, Levy J, Murray KF, Oliva-Hemker M, Rosh JR, Tolia V, Zholudev A, Vanderhoof JA, Hibberd PL.
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Source: Inflammatory Bowel Diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16116318&query_hl=1&itool=pubmed_docsum •
Absorption of the oral bisphosphonate alendronate in osteoporotic patients with Crohn's disease. Author(s): Cremers SC, van Hogezand R, Banffer D, den Hartigh J, Vermeij P, Papapoulos SE, Hamdy NA. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15959617&query_hl=1&itool=pubmed_docsum
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Acupuncture and moxibustion in the treatment of active Crohn's disease: a randomized controlled study. Author(s): Joos S, Brinkhaus B, Maluche C, Maupai N, Kohnen R, Kraehmer N, Hahn EG, Schuppan D. Source: Digestion. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15114043&query_hl=1&itool=pubmed_docsum
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Advances in therapeutic approaches to ulcerative colitis and Crohn's disease. Author(s): Travis S. Source: Current Gastroenterology Reports. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16313878&query_hl=1&itool=pubmed_docsum
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Anal carcinoma occurring in Crohn's disease patients with chronic anal fistula. Author(s): Ficari F, Fazi M, Garcea A, Nesi G, Tonelli F. Source: Suppl Tumori. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16437885&query_hl=1&itool=pubmed_docsum
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Bone turnover and nutritional status in Crohn's disease: relationship to circulating mononuclear cell function and response to fish oil and antioxidants. Author(s): Trebble TM. Source: The Proceedings of the Nutrition Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15960863&query_hl=1&itool=pubmed_docsum
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Crohn's disease is associated with a toll-like receptor-9 polymorphism. Author(s): Torok HP, Glas J, Tonenchi L, Bruennler G, Folwaczny M, Folwaczny C. Source: Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15236225&query_hl=1&itool=pubmed_docsum
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Crohn's disease leading to bowel cancer may be avoided by consumption of soya isoflavones: adjunct-chemotherapy with oxaliplatin. Author(s): Wiseman A. Source: Medical Hypotheses. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16431034&query_hl=1&itool=pubmed_docsum
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Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use. Author(s): Gilman J, Shanahan F, Cashman KD. Source: European Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16493452&query_hl=1&itool=pubmed_docsum
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Dietary sources of inorganic microparticles and their intake in healthy subjects and patients with Crohn's disease. Author(s): Lomer MC, Hutchinson C, Volkert S, Greenfield SM, Catterall A, Thompson RP, Powell JJ. Source: The British Journal of Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15613257&query_hl=1&itool=pubmed_docsum
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Does adjuvant nutritional support diminish steroid dependency in Crohn disease? Author(s): Verma S, Holdsworth CD, Giaffer MH. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11336163&query_hl=1&itool=pubmed_docsum
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Effect of fish oil enriched enteral diet on inflammatory bowel disease tissues in organ culture: differential effects on ulcerative colitis and Crohn's disease. Author(s): Meister D, Ghosh S. Source: World Journal of Gastroenterology : Wjg. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16437718&query_hl=1&itool=pubmed_docsum
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Effect of psychotherapy and relaxation on the psychosocial and somatic course of Crohn's disease: main results of the German Prospective Multicenter Psychotherapy Treatment study on Crohn's Disease. Author(s): Keller W, Pritsch M, Von Wietersheim J, Scheib P, Osborn W, Balck F, Dilg R, Schmelz-Schumacher E, Doppl W, Jantschek G, Deter HC; The German Study Group on Psychosocial Intervention in Crohn's Disease. Source: Journal of Psychosomatic Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15193965&query_hl=1&itool=pubmed_docsum
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Enteral nutrition and microflora in pediatric Crohn's disease. Author(s): Lionetti P, Callegari ML, Ferrari S, Cavicchi MC, Pozzi E, de Martino M, Morelli L.
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Source: Jpen. Journal of Parenteral and Enteral Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15980280&query_hl=1&itool=pubmed_docsum •
Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Author(s): Shoda R, Matsueda K, Yamato S, Umeda N. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8615358&query_hl=1&itool=pubmed_docsum
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European evidence based consensus on the diagnosis and management of Crohn's disease: special situations. Author(s): Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P, O'Morain C, Anwar MM, Freitas JL, Mouzas IA, Baert F, Mitchell R, Hawkey CJ; European Crohn's and Colitis Organisation. Source: Gut. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16481630&query_hl=1&itool=pubmed_docsum
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Fatty acid compositions of lipids in mesenteric adipose tissue and lymphoid cells in patients with and without Crohn's disease and their therapeutic implications. Author(s): Westcott E, Windsor A, Mattacks C, Pond C, Knight S. Source: Inflammatory Bowel Diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16116316&query_hl=1&itool=pubmed_docsum
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Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease. Author(s): Erichsen K, Hausken T, Ulvik RJ, Svardal A, Berstad A, Berge RK. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12795468&query_hl=1&itool=pubmed_docsum
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Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease. Author(s): Trebble TM, Arden NK, Wootton SA, Calder PC, Mullee MA, Fine DR, Stroud MA. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15531659&query_hl=1&itool=pubmed_docsum
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FOSter your intestinal flora: prebiotics for Crohn's disease. Author(s): Katz JA.
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Source: Inflammatory Bowel Diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16670532&query_hl=1&itool=pubmed_docsum •
Helical CT of the small bowel with an alternative oral contrast material in patients with Crohn disease. Author(s): Doerfler OC, Ruppert-Kohlmayr AJ, Reittner P, Hinterleitner T, Petritsch W, Szolar DH. Source: Abdominal Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12719900&query_hl=1&itool=pubmed_docsum
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High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial. Author(s): Trebble TM, Stroud MA, Wootton SA, Calder PC, Fine DR, Mullee MA, Moniz C, Arden NK. Source: The British Journal of Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16115360&query_hl=1&itool=pubmed_docsum
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Human defensins in Crohn's disease. Author(s): Wehkamp J, Fellermann K, Stange EF. Source: Chem Immunol Allergy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15976487&query_hl=1&itool=pubmed_docsum
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Hyperresponsiveness of the mucosal barrier in Crohn's disease is not tumor necrosis factor-dependent. Author(s): Suenaert P, Bulteel V, Vermeire S, Noman M, Van Assche G, Rutgeerts P. Source: Inflammatory Bowel Diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15973122&query_hl=1&itool=pubmed_docsum
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Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial. Author(s): Marteau P, Lemann M, Seksik P, Laharie D, Colombel JF, Bouhnik Y, Cadiot G, Soule JC, Bourreille A, Metman E, Lerebours E, Carbonnel F, Dupas JL, Veyrac M, Coffin B, Moreau J, Abitbol V, Blum-Sperisen S, Mary JY. Source: Gut. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16377775&query_hl=1&itool=pubmed_docsum
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Inflammatory bowel disease. Part II: Crohn's disease--pathophysiology and conventional and alternative treatment options. Author(s): Head K, Jurenka JS.
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Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15656711&query_hl=1&itool=pubmed_docsum •
Insulin-like growth factors (IGFs) and IGF binding proteins in active Crohn's disease treated with omega-3 or omega-6 fatty acids and corticosteroids. Author(s): Eivindson M, Gronbaek H, Nielsen JN, Frystyk J, Flyvbjerg A, Jorgensen L, Vind I, Munkholm P, Jensen S, Brandslund I, Hey H. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16265778&query_hl=1&itool=pubmed_docsum
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Is an increased intestinal permeability a valid predictor of relapse in Crohn disease? Author(s): Jorgensen J, Ranlov PJ, Bjerrum PJ, Diemer H, Bisgaard K, Elsborg L. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11346207&query_hl=1&itool=pubmed_docsum
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Lactobacillus casei DN-114 001 inhibits the ability of adherent-invasive Escherichia coli isolated from Crohn's disease patients to adhere to and to invade intestinal epithelial cells. Author(s): Ingrassia I, Leplingard A, Darfeuille-Michaud A. Source: Applied and Environmental Microbiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15932981&query_hl=1&itool=pubmed_docsum
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Lactobacillus GG in inducing and maintaining remission of Crohn's disease. Author(s): Schultz M, Timmer A, Herfarth HH, Sartor RB, Vanderhoof JA, Rath HC. Source: Bmc Gastroenterology [electronic Resource]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15113451&query_hl=1&itool=pubmed_docsum
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Low serum concentrations of insulin-like growth factor-I in children with active Crohn disease: effect of enteral nutritional support and glutamine supplementation. Author(s): Akobeng AI, Clayton PE, Miller V, Hall CM, Thomas AG. Source: Scandinavian Journal of Gastroenterology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12523592&query_hl=1&itool=pubmed_docsum
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Mineral balance during nutritional supplementation in adolescents with Crohn disease and growth failure. Author(s): Motil KJ, Altchuler SI, Grand RJ. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4032140&query_hl=1&itool=pubmed_docsum
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Novel strategies to attenuate immune activation in Crohn's disease. Author(s): Bamias G, Cominelli F.
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Source: Current Opinion in Pharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16753341&query_hl=1&itool=pubmed_docsum •
Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Author(s): Nielsen AA, Jorgensen LG, Nielsen JN, Eivindson M, Gronbaek H, Vind I, Hougaard DM, Skogstrand K, Jensen S, Munkholm P, Brandslund I, Hey H. Source: Alimentary Pharmacology & Therapeutics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16305726&query_hl=1&itool=pubmed_docsum
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Perinodal adipose tissue and fatty acid composition of lymphoid tissues in patients with and without Crohn's disease and their implications for the etiology and treatment of CD. Author(s): Westcott ED, Mattacks CA, Windsor AC, Knight SC, Pond CM. Source: Annals of the New York Academy of Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17057221&query_hl=1&itool=pubmed_docsum
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Peripheral blood mononuclear cell fatty acid composition and inflammatory mediator production in adult Crohn's disease. Author(s): Trebble TM, Arden NK, Wootton SA, Mullee MA, Calder PC, Burdge GC, Fine DR, Stroud MA. Source: Clinical Nutrition (Edinburgh, Lothian). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15297102&query_hl=1&itool=pubmed_docsum
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Positioning novel biologic, probiotic, and apheresis therapies for Crohn's disease and ulcerative colitis. Author(s): Egan LJ, Sandborn WJ. Source: Current Gastroenterology Reports. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16313879&query_hl=1&itool=pubmed_docsum
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Postoperative Crohn's disease. Author(s): Penner RM, Madsen KL, Fedorak RN. Source: Inflammatory Bowel Diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16043993&query_hl=1&itool=pubmed_docsum
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Primary Epstein-Barr virus-associated Hodgkin disease of the ileum complicating Crohn disease. Author(s): Li S, Borowitz MJ. Source: Archives of Pathology & Laboratory Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11231497&query_hl=1&itool=pubmed_docsum
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Primary gastric mantle cell lymphoma in a patient with long standing history of Crohn's disease. Author(s): Raderer M, Puspok A, Birkner T, Streubel B, Chott A. Source: Leukemia & Lymphoma. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15359648&query_hl=1&itool=pubmed_docsum
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Probiotics (VSL#3) in arthralgia in patients with ulcerative colitis and Crohn's disease: a pilot study. Author(s): Karimi O, Pena AS, van Bodegraven AA. Source: Drugs Today (Barc). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16193098&query_hl=1&itool=pubmed_docsum
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Probiotics for Crohn's disease: what have we learned? Author(s): Prantera C. Source: Gut. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16698749&query_hl=1&itool=pubmed_docsum
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Probiotics for maintenance of remission in Crohn's disease. Author(s): Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F. Source: Cochrane Database Syst Rev. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17054217&query_hl=1&itool=pubmed_docsum
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Saccharomyces boulardii in Crohn's disease: effect on anti-Saccharomyces cerevisiae antibodies and intestinal permeability. Author(s): Joossens S, Suenaert P, Noman M, Vermeire S, Rutgeerts P. Source: Inflammatory Bowel Diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16116324&query_hl=1&itool=pubmed_docsum
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Seasonality of vitamin D status and bone turnover in patients with Crohn's disease. Author(s): McCarthy D, Duggan P, O'Brien M, Kiely M, McCarthy J, Shanahan F, Cashman KD. Source: Alimentary Pharmacology & Therapeutics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15854168&query_hl=1&itool=pubmed_docsum
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The use of enteral nutrition in the management of Crohn's disease in adults. Author(s): Dray X, Marteau P. Source: Jpen. Journal of Parenteral and Enteral Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15980279&query_hl=1&itool=pubmed_docsum
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Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized,
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placebo-controlled study. Author(s): Romano C, Cucchiara S, Barabino A, Annese V, Sferlazzas C. Source: World Journal of Gastroenterology : Wjg. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16437657&query_hl=1&itool=pubmed_docsum
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://health.aol.com/healthyliving/althealth
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/naturalmedicine.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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Open Directory Project: http://dmoz.org/Health/Alternative/
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to Crohn 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: •
General Overview Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.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
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Diarrhea Source: Healthnotes, Inc.; www.healthnotes.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 Irritable Bowel Syndrome Source: Healthnotes, Inc.; www.healthnotes.com 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 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 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
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Homeopathy Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com 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 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 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 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
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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 Sulfasalazine Source: Healthnotes, Inc.; www.healthnotes.com Witch Hazel Alternative names: Hamamelis virginiana Source: Healthnotes, Inc.; www.healthnotes.com
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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 3. PATENTS ON CROHN 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.7 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 disease“ (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Crohn disease, we have not necessarily excluded non-medical patents in this bibliography.
Patent Applications on Crohn Disease As of December 2000, U.S. patent applications are open to public viewing.8 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 disease:
7Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 8 This has been a common practice outside the United States prior to December 2000.
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•
Diagnostic microarray for inflammatory bowel disease, crohn's disease and ulcerative colitis Inventor(s): Liu, Zhiyun; (Houston, TX), Mannick, Elizabeth E.; (New Orleans, LA), Serrano, Maria-Stella; (River Ridge, LA) Correspondence: Patent Department; Taylor, Porter, Brooks & Phillips, L.L.P; P.O. Box 2471; Baton Rouge; LA; 70821-2471; US Patent Application Number: 20040077020 Date filed: November 20, 2003 Abstract: Using RNA samples from mononuclear blood cells, gene sequences were identified that can be used to identify patients with IBD, and then distinguish patients with Crohn's disease from those with ulcerative colitis. Sequences were identified whose overexpression was distinct to patients with IBD, Crohn's disease, and ulcerative colitis when compared to patients with non-IBD intestinal disorders. Additionally, cluster analysis was used to identify twenty-five sequences that are IBD-related, and whose transcription pattern can be used in a microarray analysis to identify patients with IBD with a sensitivity of 84% and a specificity of 100%. Cluster analysis also identified thirty-six genes that could be used to distinguish patients with Crohn's disease from those with ulcerative colitis with a sensitivity of 89% and a specificity of 80%. Excerpt(s): The benefit of the filing dates of provisional applications Nos. 60/286,602 filed Apr. 26, 2001, 60/264,909 filed Jan. 29, 2001, and 60/250,303 filed Nov. 30, 2000 are claimed under 35 U.S.C.sctn. 119(e) in the United States, and are claimed under applicable treaties and conventions in all countries. This invention pertains to a method that uses DNA microarray hybridization to identify patients with inflammatory bowel disease, and to distinguish Crohn's disease from ulcerative colitis. Despite greater than fifty years of clinical experience with Crohn's disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), the precise etiology of these diseases remains unknown and the morbidity they engender high. Further, between 10-15% of patients cannot be accurately diagnosed as having either Crohn's disease or ulcerative colitis and are classified as indeterminate colitis, making treatment decisions and evaluation of long-term prognosis difficult. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for the preparation of a pharmaceutical composition comprising 5aminosalicylic acid for use in treatment of ulcerative colitis and crohn's disease Inventor(s): Jepsen, Svenn Kluver; (Holte, DK) Correspondence: Steptoe & Johnson Llp; 1330 Connecticut AVE., NW; Washington; DC; 20036; US Patent Application Number: 20030138495 Date filed: October 11, 2002 Abstract: The present invention concerns a new method of preparing granules comprising 5-aminosalicylic acid and a new method of preparing a pharmaceutical composition for the treatment of ulcerative colitis or Crohn's disease by oral administration comprising as active ingredient 5-aminosalicylic acid.
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Excerpt(s): The present invention relates to a method of preparing a pharmaceutical composition useful for the treatment of ulcerative colitis and Crohn's disease, currently denominated "inflammatory bowel diseases" (IBD). More particular, the invention relates to a new method of producing granules comprising 5-aminosalisylic acid (5ASA) for use in the preparation of solid oral dosage forms. Ulcerative colitis is a chronic inflammatory disease of the colon of unknown etiology. In its acute stages it resembles an infectious disease, but no microorganism has been definitively established as its cause. The disease causes inflammations of the mucosa of the colon, with extension to the submucosa in severe cases. Typically, not only the colon, but also the rectum is attacked, but only rarely is the ileum involved. The ulcer formation and its extent vary with the developmental stage of the disease, but can often be determined macroscopically (sigmoidoscopy and colonoscopy). The related disease, Crohn's disease, also known as regional enteritis or colitis granulomatosa, is most frequently located in the small intestine (small bowel), especially in the ileum, but may also affect the jejunum and any part of the colon, including the rectum. In the latter case the differentiation of Crohn's disease from ulcerative colitis gives rise to great diagnostic problems. Generally, the inflammation differs from that of ulcerative colitis by progressing to layers deeper than the mucosa and affecting the epithelium to a lesser degree. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with Crohn 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 disease (or a synonym) 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 disease. You can also use this procedure to view pending patent applications concerning Crohn disease. Simply go back to http://www.uspto.gov/patft/index.html. Select Quick Search under Published Applications. Then proceed with the steps listed above.
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CHAPTER 4. BOOKS ON CROHN DISEASE Overview This chapter provides bibliographic book references relating to Crohn disease. In addition to online booksellers such as www.amazon.com and www.bn.com, the National Library of Medicine is an excellent source for book titles on Crohn disease. Your local medical library also may have these titles available for loan.
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 disease at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Crohn disease” (or a synonym) in their titles. The following is indicative of the results you might find when searching for Crohn disease (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
100 Q&A About Crohn's Disease and Ulcerative Colitis: A Lahey Clinic Guide (100 Questions & Answers about.) Andrew S. Warner (2007); ISBN: 0763739677; http://www.amazon.com/exec/obidos/ASIN/0763739677/icongroupinterna
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Adalimumab maintains Crohn's disease remission; the subcutaneously injected drug is currently approved by the FDA for the treatment of arthritis.(Digestive. An article from: Family Practice News Mitchel L. Zoler (2006); ISBN: B000E6EQ78; http://www.amazon.com/exec/obidos/ASIN/B000E6EQ78/icongroupinterna
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Atypical presentation of Crohn disease in an Asian-Indian patient.(Letter to the editor): An article from: Southern Medical Journal Sagar U. Nigwekar and Kevin J. Casey (2006); ISBN: B000M545AY; http://www.amazon.com/exec/obidos/ASIN/B000M545AY/icongroupinterna
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Bailliere's International Practice and Research: Clinical Gastroenterology: Crohn's Disease (Bailliere's International Practice) R.N. Allan and M.R.B. Keighly (1998); ISBN:
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0702024821; http://www.amazon.com/exec/obidos/ASIN/0702024821/icongroupinterna •
Coping With Crohn's Disease and Ulcerative Colitis (Coping) Christina Potter (2003); ISBN: 0823939626; http://www.amazon.com/exec/obidos/ASIN/0823939626/icongroupinterna
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Daily Telegraph Crohn's Disease and Ulce Fred Saibil (2003); ISBN: B000K6RURK; http://www.amazon.com/exec/obidos/ASIN/B000K6RURK/icongroupinterna
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Eating Right For a Bad Gut: compl Nutritional GT Ileitis Colitis Crohn's Disease & Inflammatory Bowel Diseas (Plume Books) James Scala (1992); ISBN: 0452267668; http://www.amazon.com/exec/obidos/ASIN/0452267668/icongroupinterna
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Everything You Need to Know About Crohn's Disease and Ulcerative Colitis (Need to Know Library) Sandra Giddens and Owen Giddens (2003); ISBN: 0823939960; http://www.amazon.com/exec/obidos/ASIN/0823939960/icongroupinterna
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Familial Crohn's disease is more severe if tied to NOD2: data on 129 patients. (Gastroenterology).: An article from: Internal Medicine News Bruce Jancin (2005); ISBN: B0008DCBN8; http://www.amazon.com/exec/obidos/ASIN/B0008DCBN8/icongroupinterna
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First Year: Crohn's Disease and Ulcerati Jill Sklar (2004); ISBN: B000K7M76S; http://www.amazon.com/exec/obidos/ASIN/B000K7M76S/icongroupinterna
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From chronic illness to hope. (woman with Crohn's disease cured with antibiotics): An article from: Medical Update (2005); ISBN: B00092WFE8; http://www.amazon.com/exec/obidos/ASIN/B00092WFE8/icongroupinterna
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Increase in Crohn's disease might be linked to modern refrigeration.: An article from: On The Plate (2005); ISBN: B0008GA49S; http://www.amazon.com/exec/obidos/ASIN/B0008GA49S/icongroupinterna
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Inflammatory Bowel Disease: Pathophysiology, diagnosis and treatment of Crohn's disease and ulcerative colitis Stefan Schreiber, Susanne Wedel, C. Reuter, and P. Reuter (1999); ISBN: 3540148167; http://www.amazon.com/exec/obidos/ASIN/3540148167/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 William B. Salt II and 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) Chr.J Mulder and G.N. Tytgat (1899); ISBN: 0792320263; http://www.amazon.com/exec/obidos/ASIN/0792320263/icongroupinterna
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Joanna's story. (teenager helps young people with colitis and Crohn's disease prepare for surgery): An article from: Ostomy Quarterly Joanna Welte and Sharon Welte (2005); ISBN: B00093UKGM; http://www.amazon.com/exec/obidos/ASIN/B00093UKGM/icongroupinterna
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Learning Sickness: A Year With Crohn's Disease (Capital Discovery) Jim Lang (2005); ISBN: 1933102012; http://www.amazon.com/exec/obidos/ASIN/1933102012/icongroupinterna
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Living with Crohn's Disease (Overcoming Common Problems Series) Joan Gomez (2000); ISBN: 0859698203; http://www.amazon.com/exec/obidos/ASIN/0859698203/icongroupinterna
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•
Managing Your Child's Crohn's Disease and Ulcerative Colitis Keith J. Benkov and Harland S. Winter (1996); ISBN: 1571010238; http://www.amazon.com/exec/obidos/ASIN/1571010238/icongroupinterna
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MED-9. Crohn's disease presenting as a life-threatening retropharyngeal abscess.(Section on Internal Medicine): An article from: Southern Medical Journal Saima Ansari, Shakeel Ahmed, James Szalados, and Joanne Hessney (2005); ISBN: B0009GO80I; http://www.amazon.com/exec/obidos/ASIN/B0009GO80I/icongroupinterna
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Natalizumab can maintain Crohn's disease response: after 32 weeks, response rates were 61% with natalizumab and 29% with placebo.(News): An article from: Internal Medicine News Mitchel L. Zoler (2005); ISBN: B0009GNYRQ; http://www.amazon.com/exec/obidos/ASIN/B0009GNYRQ/icongroupinterna
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Out of the trenches: battling Crohn's disease and finding a very important ally.: An article from: Ostomy Quarterly Judith Moore-Hepburn (2005); ISBN: B00098B8C2; http://www.amazon.com/exec/obidos/ASIN/B00098B8C2/icongroupinterna
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Pathogenic mechanisms in Crohn's Disease - immunological alterations measured by whole blood mitogenic responses, IL-1 and IL-2 assays Khalid Z Matalka (1988); ISBN: B0007BJT22; http://www.amazon.com/exec/obidos/ASIN/B0007BJT22/icongroupinterna
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Recent Advances in Crohn's Disease (Developments in Gastroenterology) A.S. Peña, I.T. Weterman, C.C. Booth, and W. Strober (1899); ISBN: 9024724759; http://www.amazon.com/exec/obidos/ASIN/9024724759/icongroupinterna
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Regular cancer screening needed in Crohn's disease patients; recommendations not followed.(News): An article from: Family Practice News Norra MacReady (2005); ISBN: B00082U384; http://www.amazon.com/exec/obidos/ASIN/B00082U384/icongroupinterna
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The Complete Crohnie Handbook: A Comprehensive Guide for the Crohn's Disease Patient Robert R. Pilkington (2003); ISBN: 0971887101; http://www.amazon.com/exec/obidos/ASIN/0971887101/icongroupinterna
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The Crohn's Disease and Ulcerative Colitis Fact Book Crohn's & Colitis Foundation, Peter A. Banks, Daniel H. Present, and Penny Steiner (1983); ISBN: 0684179679; http://www.amazon.com/exec/obidos/ASIN/0684179679/icongroupinterna
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Treatment trials for Crohn's disease and ulcerative colitis. (Prevention Progress).: An article from: Ostomy Quarterly Keith Carlson (2005); ISBN: B0008F8HFW; http://www.amazon.com/exec/obidos/ASIN/B0008F8HFW/icongroupinterna
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Understanding Crohn Disease and Ulcerative Colitis Jon, Zonderman and Ronald, S. Vender (2006); ISBN: 1578062039; http://www.amazon.com/exec/obidos/ASIN/1578062039/icongroupinterna
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What to Eat with IBD: A Comprehensive Nutrition and Recipe Guide for Crohn's Disease and Ulcerative Colitis Tracie M Dalessandro MS RD CDN (2006); ISBN: 0595397492; http://www.amazon.com/exec/obidos/ASIN/0595397492/icongroupinterna
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CHAPTER 5. 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 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 Pharmacopeia 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 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
Researching Medications
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Crohn disease: Infliximab •
Systemic - U.S. Brands: Remicade http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203667.html
Mesalamine •
Oral - U.S. Brands: Asacol; Pentasa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202734.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 The term “orphan drug” refers to a product that treats a rare disease affecting fewer than 200,000 Americans. The Orphan Drug Act was signed into law on January 4, 1983. Since the Orphan Drug Act passed, over 100 orphan drugs and biological products have been brought
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to market.9 The Office of Orphan Products Development (OOPD), a service of the U.S. Food and Drug Administration (FDA), provides access to lists of orphan designations and approvals at the following Web site: http://www.fda.gov/orphan/designat/list.htm. The following is a list of products currently receiving Orphan Designation from the FDA which have designated indications for Crohn 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
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CDP571 http://www.rarediseases.org/nord/search/nodd_full?code=860
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TAK-603 http://www.rarediseases.org/nord/search/nodd_full?code=921
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Infliximab (trade name: Remicade) http://www.rarediseases.org/nord/search/nodd_full?code=958
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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.
9 Adapted
from the U.S. Food and Drug Administration: http://www.fda.gov/cder/handbook/orphan.htm.
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APPENDIX A. HELP ME UNDERSTAND GENETICS Overview This appendix presents basic information about genetics in clear language and provides links to online resources.10
The Basics: Genes and How They Work This section gives you information on the basics of cells, DNA, genes, chromosomes, and proteins. What Is a Cell? Cells are the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialized functions. Cells also contain the body’s hereditary material and can make copies of themselves. Cells have many parts, each with a different function. Some of these parts, called organelles, are specialized structures that perform certain tasks within the cell. Human cells contain the following major parts, listed in alphabetical order: •
Cytoplasm: The cytoplasm is fluid inside the cell that surrounds the organelles.
•
Endoplasmic reticulum (ER): This organelle helps process molecules created by the cell and transport them to their specific destinations either inside or outside the cell.
•
Golgi apparatus: The golgi apparatus packages molecules processed by the endoplasmic reticulum to be transported out of the cell.
•
Lysosomes and peroxisomes: These organelles are the recycling center of the cell. They digest foreign bacteria that invade the cell, rid the cell of toxic substances, and recycle worn-out cell components.
10 This appendix is an excerpt from the National Library of Medicine’s handbook, Help Me Understand Genetics. For the full text of the Help Me Understand Genetics handbook, see http://ghr.nlm.nih.gov/handbook.
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•
Mitochondria: Mitochondria are complex organelles that convert energy from food into a form that the cell can use. They have their own genetic material, separate from the DNA in the nucleus, and can make copies of themselves.
•
Nucleus: The nucleus serves as the cell’s command center, sending directions to the cell to grow, mature, divide, or die. It also houses DNA (deoxyribonucleic acid), the cell’s hereditary material. The nucleus is surrounded by a membrane called the nuclear envelope, which protects the DNA and separates the nucleus from the rest of the cell.
•
Plasma membrane: The plasma membrane is the outer lining of the cell. It separates the cell from its environment and allows materials to enter and leave the cell.
•
Ribosomes: Ribosomes are organelles that process the cell’s genetic instructions to create proteins. These organelles can float freely in the cytoplasm or be connected to the endoplasmic reticulum. What Is DNA?
DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder. An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.
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DNA is a double helix formed by base pairs attached to a sugar-phosphate backbone. What Is Mitochondrial DNA? Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. This genetic material is known as mitochondrial DNA or mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Each cell contains hundreds to thousands of mitochondria, which are located in the fluid that surrounds the nucleus (the cytoplasm). Mitochondria produce energy through a process called oxidative phosphorylation. This process uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell’s main energy source. A set of enzyme complexes, designated as complexes I-V, carry out oxidative phosphorylation within mitochondria. In addition to energy production, mitochondria play a role in several other cellular activities. For example, mitochondria help regulate the self-destruction of cells (apoptosis). They are also necessary for the production of substances such as cholesterol and heme (a component of hemoglobin, the molecule that carries oxygen in the blood). Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. The remaining genes provide instructions for making molecules called transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), which are chemical cousins of
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DNA. These types of RNA help assemble protein building blocks (amino acids) into functioning proteins. What Is a Gene? A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes. Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.
Genes are made up of DNA. Each chromosome contains many genes. What Is a Chromosome? In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure. Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled the “p arm.” The long arm of the chromosome is labeled the “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes.
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DNA and histone proteins are packaged into structures called chromosomes. How Many Chromosomes Do People Have? In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. Twentytwo of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.
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The 22 autosomes are numbered by size. The other two chromosomes, X and Y, are the sex chromosomes. This picture of the human chromosomes lined up in pairs is called a karyotype. How Do Geneticists Indicate the Location of a Gene? Geneticists use maps to describe the location of a particular gene on a chromosome. One type of map uses the cytogenetic location to describe a gene’s position. The cytogenetic location is based on a distinctive pattern of bands created when chromosomes are stained with certain chemicals. Another type of map uses the molecular location, a precise description of a gene’s position on a chromosome. The molecular location is based on the sequence of DNA building blocks (base pairs) that make up the chromosome. Cytogenetic Location Geneticists use a standardized way of describing a gene’s cytogenetic location. In most cases, the location describes the position of a particular band on a stained chromosome: 17q12 It can also be written as a range of bands, if less is known about the exact location: 17q12-q21 The combination of numbers and letters provide a gene’s “address” on a chromosome. This address is made up of several parts: •
The chromosome on which the gene can be found. The first number or letter used to describe a gene’s location represents the chromosome. Chromosomes 1 through 22 (the autosomes) are designated by their chromosome number. The sex chromosomes are designated by X or Y.
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•
The arm of the chromosome. Each chromosome is divided into two sections (arms) based on the location of a narrowing (constriction) called the centromere. By convention, the shorter arm is called p, and the longer arm is called q. The chromosome arm is the second part of the gene’s address. For example, 5q is the long arm of chromosome 5, and Xp is the short arm of the X chromosome.
•
The position of the gene on the p or q arm. The position of a gene is based on a distinctive pattern of light and dark bands that appear when the chromosome is stained in a certain way. The position is usually designated by two digits (representing a region and a band), which are sometimes followed by a decimal point and one or more additional digits (representing sub-bands within a light or dark area). The number indicating the gene position increases with distance from the centromere. For example: 14q21 represents position 21 on the long arm of chromosome 14. 14q21 is closer to the centromere than 14q22.
Sometimes, the abbreviations “cen” or “ter” are also used to describe a gene’s cytogenetic location. “Cen” indicates that the gene is very close to the centromere. For example, 16pcen refers to the short arm of chromosome 16 near the centromere. “Ter” stands for terminus, which indicates that the gene is very close to the end of the p or q arm. For example, 14qter refers to the tip of the long arm of chromosome 14. (“Tel” is also sometimes used to describe a gene’s location. “Tel” stands for telomeres, which are at the ends of each chromosome. The abbreviations “tel” and “ter” refer to the same location.)
The CFTR gene is located on the long arm of chromosome 7 at position 7q31.2.
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Molecular Location The Human Genome Project, an international research effort completed in 2003, determined the sequence of base pairs for each human chromosome. This sequence information allows researchers to provide a more specific address than the cytogenetic location for many genes. A gene’s molecular address pinpoints the location of that gene in terms of base pairs. For example, the molecular location of the APOE gene on chromosome 19 begins with base pair 50,100,901 and ends with base pair 50,104,488. This range describes the gene’s precise position on chromosome 19 and indicates the size of the gene (3,588 base pairs). Knowing a gene’s molecular location also allows researchers to determine exactly how far the gene is from other genes on the same chromosome. Different groups of researchers often present slightly different values for a gene’s molecular location. Researchers interpret the sequence of the human genome using a variety of methods, which can result in small differences in a gene’s molecular address. For example, the National Center for Biotechnology Information (NCBI) identifies the molecular location of the APOE gene as base pair 50,100,901 to base pair 50,104,488 on chromosome 19. The Ensembl database identifies the location of this gene as base pair 50,100,879 to base pair 50,104,489 on chromosome 19. Neither of these addresses is incorrect; they represent different interpretations of the same data. For consistency, Genetics Home Reference presents data from NCBI for the molecular location of genes. What Are Proteins and What Do They Do? Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs. Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function.
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Examples of Protein Functions Proteins can be described according to their large range of functions in the body, listed in alphabetical order: Function Antibody
Description Antibodies bind to specific foreign particles, such as viruses and bacteria, to help protect the body.
Example Immunoglobulin G (IgG)
Enzyme
Enzymes carry out almost all of the thousands of chemical reactions that take place in cells. They also assist with the formation of new molecules by reading the genetic information stored in DNA.
Phenylalanine hydroxylase
Messenger
Messenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, tissues, and organs.
Growth hormone
Structural component
These proteins provide structure and support for cells. On a larger scale, they also allow the body to move. These proteins bind and carry atoms and small molecules within cells and throughout the body.
Actin
Transport/storage
Ferritin
How Does a Gene Make a Protein? Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression. During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm. Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for
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one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid). The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology. It is so important that it is sometimes called the “central dogma.”
Through the processes of transcription and translation, information from genes is used to make proteins.
Can Genes Be Turned On and Off in Cells? Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood. Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.
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How Do Cells Divide? There are two types of cell division: mitosis and meiosis. Most of the time when people refer to “cell division,” they mean mitosis, the process of making new body cells. Meiosis is the type of cell division that creates egg and sperm cells. Mitosis is a fundamental process for life. During mitosis, a cell duplicates all of its contents, including its chromosomes, and splits to form two identical daughter cells. Because this process is so critical, the steps of mitosis are carefully controlled by a number of genes. When mitosis is not regulated correctly, health problems such as cancer can result. The other type of cell division, meiosis, ensures that humans have the same number of chromosomes in each generation. It is a two-step process that reduces the chromosome number by half—from 46 to 23—to form sperm and egg cells. When the sperm and egg cells unite at conception, each contributes 23 chromosomes so the resulting embryo will have the usual 46. Meiosis also allows genetic variation through a process of DNA shuffling while the cells are dividing.
Mitosis and meiosis, the two types of cell division. How Do Genes Control the Growth and Division of Cells? A variety of genes are involved in the control of cell growth and division. The cell cycle is the cell’s way of replicating itself in an organized, step-by-step fashion. Tight regulation of this process ensures that a dividing cell’s DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. The cycle has checkpoints (also called restriction points), which allow certain genes to check for mistakes and halt the cycle for repairs if something goes wrong.
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If a cell has an error in its DNA that cannot be repaired, it may undergo programmed cell death (apoptosis). Apoptosis is a common process throughout life that helps the body get rid of cells it doesn’t need. Cells that undergo apoptosis break apart and are recycled by a type of white blood cell called a macrophage. Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues. Cancer results from a disruption of the normal regulation of the cell cycle. When the cycle proceeds without control, cells can divide without order and accumulate genetic defects that can lead to a cancerous tumor.
Genetic Mutations and Health This section presents basic information about gene mutations, chromosomal changes, and conditions that run in families.11 What Is a Gene Mutation and How Do Mutations Occur? A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome. Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. Mutations that are passed from parent to child are called hereditary mutations or germline mutations (because they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present throughout a person’s life in virtually every cell in the body. Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder. Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation. Mutations may also occur in a single cell within an early embryo. As all the cells divide during growth and development, the individual will have some cells with the mutation and some cells without the genetic change. This situation is called mosaicism. Some genetic changes are very rare; others are common in the population. Genetic changes that occur in more than 1 percent of the population are called polymorphisms. They are common enough to be considered a normal variation in the DNA. Polymorphisms are 11
This section has been adapted from the National Library of Medicine’s handbook, Help Me Understand Genetics, which presents basic information about genetics in clear language and provides links to online resources: http://ghr.nlm.nih.gov/handbook.
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responsible for many of the normal differences between people such as eye color, hair color, and blood type. Although many polymorphisms have no negative effects on a person’s health, some of these variations may influence the risk of developing certain disorders. How Can Gene Mutations Affect Health and Development? To function correctly, each cell depends on thousands of proteins to do their jobs in the right places at the right times. Sometimes, gene mutations prevent one or more of these proteins from working properly. By changing a gene’s instructions for making a protein, a mutation can cause the protein to malfunction or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition. A condition caused by mutations in one or more genes is called a genetic disorder. In some cases, gene mutations are so severe that they prevent an embryo from surviving until birth. These changes occur in genes that are essential for development, and often disrupt the development of an embryo in its earliest stages. Because these mutations have very serious effects, they are incompatible with life. It is important to note that genes themselves do not cause disease—genetic disorders are caused by mutations that make a gene function improperly. For example, when people say that someone has “the cystic fibrosis gene,” they are usually referring to a mutated version of the CFTR gene, which causes the disease. All people, including those without cystic fibrosis, have a version of the CFTR gene. Do All Gene Mutations Affect Health and Development? No, only a small percentage of mutations cause genetic disorders—most have no impact on health or development. For example, some mutations alter a gene’s DNA base sequence but do not change the function of the protein made by the gene. Often, gene mutations that could cause a genetic disorder are repaired by certain enzymes before the gene is expressed (makes a protein). Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, DNA repair is an important process by which the body protects itself from disease. A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a beneficial mutation could result in a protein that protects the organism from a new strain of bacteria. For More Information about DNA Repair and the Health Effects of Gene Mutations •
The University of Utah Genetic Science Learning Center provides information about genetic disorders that explains why some mutations cause disorders but others do not. (Refer to the questions in the far right column.) See http://learn.genetics.utah.edu/units/disorders/whataregd/.
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Additional information about DNA repair is available from the NCBI Science Primer. In the chapter called “What Is A Cell?”, scroll down to the heading “DNA Repair Mechanisms.” See http://www.ncbi.nlm.nih.gov/About/primer/genetics_cell.html. What Kinds of Gene Mutations Are Possible?
The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. The types of mutations include: •
Missense mutation: This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.
•
Nonsense mutation: A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.
•
Insertion: An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly.
•
Deletion: A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).
•
Duplication: A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.
•
Frameshift mutation: This type of mutation occurs when the addition or loss of DNA bases changes a gene’s reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.
•
Repeat expansion: Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated. This type of mutation can cause the resulting protein to function improperly. Can Changes in Chromosomes Affect Health and Development?
Changes that affect entire chromosomes or segments of chromosomes can cause problems with growth, development, and function of the body’s systems. These changes can affect many genes along the chromosome and alter the proteins made by those genes. Conditions caused by a change in the number or structure of chromosomes are known as chromosomal disorders. Human cells normally contain 23 pairs of chromosomes, for a total of 46 chromosomes in each cell. A change in the number of chromosomes leads to a chromosomal disorder. These
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changes can occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. A gain or loss of chromosomes from the normal 46 is called aneuploidy. The most common form of aneuploidy is trisomy, or the presence of an extra chromosome in each cell. “Tri-” is Greek for “three”; people with trisomy have three copies of a particular chromosome in each cell instead of the normal two copies. Down syndrome is an example of a condition caused by trisomy—people with Down syndrome typically have three copies of chromosome 21 in each cell, for a total of 47 chromosomes per cell. Monosomy, or the loss of one chromosome from each cell, is another kind of aneuploidy. “Mono-” is Greek for “one”; people with monosomy have one copy of a particular chromosome in each cell instead of the normal two copies. Turner syndrome is a condition caused by monosomy. Women with Turner syndrome are often missing one copy of the X chromosome in every cell, for a total of 45 chromosomes per cell. Chromosomal disorders can also be caused by changes in chromosome structure. These changes are caused by the breakage and reunion of chromosome segments when an egg or sperm cell is formed or in early fetal development. Pieces of DNA can be rearranged within one chromosome, or transferred between two or more chromosomes. The effects of structural changes depend on their size and location. Many different structural changes are possible; some cause medical problems, while others may have no effect on a person’s health. Many cancer cells also have changes in their chromosome number or structure. These changes most often occur in somatic cells (cells other than eggs and sperm) during a person’s lifetime. Can Changes in Mitochondrial DNA Affect Health and Development? Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA). In some cases, inherited changes in mitochondrial DNA can cause problems with growth, development, and function of the body’s systems. These mutations disrupt the mitochondria’s ability to generate energy efficiently for the cell. Conditions caused by mutations in mitochondrial DNA often involve multiple organ systems. The effects of these conditions are most pronounced in organs and tissues that require a lot of energy (such as the heart, brain, and muscles). Although the health consequences of inherited mitochondrial DNA mutations vary widely, frequently observed features include muscle weakness and wasting, problems with movement, diabetes, kidney failure, heart disease, loss of intellectual functions (dementia), hearing loss, and abnormalities involving the eyes and vision. Mitochondrial DNA is also prone to noninherited (somatic) mutations. Somatic mutations occur in the DNA of certain cells during a person’s lifetime, and typically are not passed to future generations. Because mitochondrial DNA has a limited ability to repair itself when it is damaged, these mutations tend to build up over time. A buildup of somatic mutations in mitochondrial DNA has been associated with some forms of cancer and an increased risk of certain age-related disorders such as heart disease, Alzheimer disease, and Parkinson
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disease. Additionally, research suggests that the progressive accumulation of these mutations over a person’s lifetime may play a role in the normal process of aging. What Are Complex or Multifactorial Disorders? Researchers are learning that nearly all conditions and diseases have a genetic component. Some disorders, such as sickle cell anemia and cystic fibrosis, are caused by mutations in a single gene. The causes of many other disorders, however, are much more complex. Common medical problems such as heart disease, diabetes, and obesity do not have a single genetic cause—they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Conditions caused by many contributing factors are called complex or multifactorial disorders. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified. By 2010, however, researchers predict they will have found the major contributing genes for many common complex disorders. What Information about a Genetic Condition Can Statistics Provide? Statistical data can provide general information about how common a condition is, how many people have the condition, or how likely it is that a person will develop the condition. Statistics are not personalized, however—they offer estimates based on groups of people. By taking into account a person’s family history, medical history, and other factors, a genetics professional can help interpret what statistics mean for a particular patient. Common Statistical Terms Some statistical terms are commonly used when describing genetic conditions and other disorders. These terms include: Statistical Term Incidence
Description The incidence of a gene mutation or a genetic disorder is the number of people who are born with the mutation or disorder in a specified group per year. Incidence is often written in the form “1 in [a number]” or as a total number of live births.
Examples About 1 in 200,000 people in the United States are born with syndrome A each year. An estimated 15,000 infants with syndrome B were born last year worldwide.
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Prevalence
The prevalence of a gene mutation or a genetic disorder is the total number of people in a specified group at a given time who have the mutation or disorder. This term includes both newly diagnosed and preexisting cases in people of any age. Prevalence is often written in the form “1 in [a number]” or as a total number of people who have a condition.
Approximately 1 in 100,000 people in the United States have syndrome A at the present time. About 100,000 children worldwide currently have syndrome B.
Mortality
Mortality is the number of deaths from a particular disorder occurring in a specified group per year. Mortality is usually expressed as a total number of deaths.
An estimated 12,000 people worldwide died from syndrome C in 2002.
Lifetime risk
Lifetime risk is the average risk of developing a particular disorder at some point during a lifetime. Lifetime risk is often written as a percentage or as “1 in [a number].” It is important to remember that the risk per year or per decade is much lower than the lifetime risk. In addition, other factors may increase or decrease a person’s risk as compared with the average.
Approximately 1 percent of people in the United States develop disorder D during their lifetimes. The lifetime risk of developing disorder D is 1 in 100.
Naming Genetic Conditions Genetic conditions are not named in one standard way (unlike genes, which are given an official name and symbol by a formal committee). Doctors who treat families with a particular disorder are often the first to propose a name for the condition. Expert working groups may later revise the name to improve its usefulness. Naming is important because it allows accurate and effective communication about particular conditions, which will ultimately help researchers find new approaches to treatment. Disorder names are often derived from one or a combination of sources: •
The basic genetic or biochemical defect that causes the condition (for example, alpha-1 antitrypsin deficiency)
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One or more major signs or symptoms of the disorder (for example, sickle cell anemia)
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The parts of the body affected by the condition (for example, retinoblastoma)
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The name of a physician or researcher, often the first person to describe the disorder (for example, Marfan syndrome, which was named after Dr. Antoine Bernard-Jean Marfan)
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A geographic area (for example, familial Mediterranean fever, which occurs mainly in populations bordering the Mediterranean Sea)
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The name of a patient or family with the condition (for example, amyotrophic lateral sclerosis, which is also called Lou Gehrig disease after a famous baseball player who had the condition).
Disorders named after a specific person or place are called eponyms. There is debate as to whether the possessive form (e.g., Alzheimer’s disease) or the nonpossessive form (Alzheimer disease) of eponyms is preferred. As a rule, medical geneticists use the nonpossessive form, and this form may become the standard for doctors in all fields of medicine. Genetics Home Reference uses the nonpossessive form of eponyms. Genetics Home Reference consults with experts in the field of medical genetics to provide the current, most accurate name for each disorder. Alternate names are included as synonyms. Naming genes The HUGO Gene Nomenclature Committee (HGNC) designates an official name and symbol (an abbreviation of the name) for each known human gene. Some official gene names include additional information in parentheses, such as related genetic conditions, subtypes of a condition, or inheritance pattern. The HGNC is a non-profit organization funded by the U.K. Medical Research Council and the U.S. National Institutes of Health. The Committee has named more than 13,000 of the estimated 20,000 to 25,000 genes in the human genome. During the research process, genes often acquire several alternate names and symbols. Different researchers investigating the same gene may each give the gene a different name, which can cause confusion. The HGNC assigns a unique name and symbol to each human gene, which allows effective organization of genes in large databanks, aiding the advancement of research. For specific information about how genes are named, refer to the HGNC’s Guidelines for Human Gene Nomenclature. Genetics Home Reference describes genes using the HGNC’s official gene names and gene symbols. Genetics Home Reference frequently presents the symbol and name separated with a colon (for example, FGFR4: Fibroblast growth factor receptor 4).
Inheriting Genetic Conditions This section gives you information on inheritance patterns and understanding risk. What Does It Mean If a Disorder Seems to Run in My Family? A particular disorder might be described as “running in a family” if more than one person in the family has the condition. Some disorders that affect multiple family members are caused by gene mutations, which can be inherited (passed down from parent to child). Other conditions that appear to run in families are not inherited. Instead, environmental factors such as dietary habits or a combination of genetic and environmental factors are responsible for these disorders.
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It is not always easy to determine whether a condition in a family is inherited. A genetics professional can use a person’s family history (a record of health information about a person’s immediate and extended family) to help determine whether a disorder has a genetic component.
Some disorders are seen in more than one generation of a family. Why Is It Important to Know My Family Medical History? A family medical history is a record of health information about a person and his or her close relatives. A complete record includes information from three generations of relatives, including children, brothers and sisters, parents, aunts and uncles, nieces and nephews, grandparents, and cousins.
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Families have many factors in common, including their genes, environment, and lifestyle. Together, these factors can give clues to medical conditions that may run in a family. By noticing patterns of disorders among relatives, healthcare professionals can determine whether an individual, other family members, or future generations may be at an increased risk of developing a particular condition. A family medical history can identify people with a higher-than-usual chance of having common disorders, such as heart disease, high blood pressure, stroke, certain cancers, and diabetes. These complex disorders are influenced by a combination of genetic factors, environmental conditions, and lifestyle choices. A family history also can provide information about the risk of rarer conditions caused by mutations in a single gene, such as cystic fibrosis and sickle cell anemia. While a family medical history provides information about the risk of specific health concerns, having relatives with a medical condition does not mean that an individual will definitely develop that condition. On the other hand, a person with no family history of a disorder may still be at risk of developing that disorder. Knowing one’s family medical history allows a person to take steps to reduce his or her risk. For people at an increased risk of certain cancers, healthcare professionals may recommend more frequent screening (such as mammography or colonoscopy) starting at an earlier age. Healthcare providers may also encourage regular checkups or testing for people with a medical condition that runs in their family. Additionally, lifestyle changes such as adopting a healthier diet, getting regular exercise, and quitting smoking help many people lower their chances of developing heart disease and other common illnesses. The easiest way to get information about family medical history is to talk to relatives about their health. Have they had any medical problems, and when did they occur? A family gathering could be a good time to discuss these issues. Additionally, obtaining medical records and other documents (such as obituaries and death certificates) can help complete a family medical history. It is important to keep this information up-to-date and to share it with a healthcare professional regularly. What Are the Different Ways in which a Genetic Condition Can Be Inherited? Some genetic conditions are caused by mutations in a single gene. These conditions are usually inherited in one of several straightforward patterns, depending on the gene involved: Inheritance Pattern Autosomal dominant
Description One mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. Autosomal dominant disorders tend to occur in every generation of an affected family.
Examples Huntington disease, neurofibromatosis type 1
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Autosomal recessive
Two mutated copies of the gene are present in each cell when a person has an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Autosomal recessive disorders are typically not seen in every generation of an affected family.
cystic fibrosis, sickle cell anemia
X-linked dominant
X-linked dominant disorders are caused by mutations in genes on the X chromosome. Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women. Families with an X-linked dominant disorder often have both affected males and affected females in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).
fragile X syndrome
X-linked recessive
X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. Families with an X-linked recessive disorder often have affected males, but rarely affected females, in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).
hemophilia, Fabry disease
Codominant
In codominant inheritance, two different versions (alleles) of a gene can be expressed, and each version makes a slightly different protein. Both alleles influence the genetic trait or determine the characteristics of the genetic condition.
ABO blood group, alpha-1 antitrypsin deficiency
Mitochondrial
This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Mitochondria, which are structures in each cell that convert molecules into energy, each contain a small amount of DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.
Leber hereditary optic neuropathy (LHON)
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Many other disorders are caused by a combination of the effects of multiple genes or by interactions between genes and the environment. Such disorders are more difficult to analyze because their genetic causes are often unclear, and they do not follow the patterns of inheritance described above. Examples of conditions caused by multiple genes or gene/environment interactions include heart disease, diabetes, schizophrenia, and certain types of cancer. Disorders caused by changes in the number or structure of chromosomes do not follow the straightforward patterns of inheritance listed above. Other genetic factors can also influence how a disorder is inherited. If a Genetic Disorder Runs in My Family, What Are the Chances That My Children Will Have the Condition? When a genetic disorder is diagnosed in a family, family members often want to know the likelihood that they or their children will develop the condition. This can be difficult to predict in some cases because many factors influence a person’s chances of developing a genetic condition. One important factor is how the condition is inherited. For example: •
Autosomal dominant inheritance: A person affected by an autosomal dominant disorder has a 50 percent chance of passing the mutated gene to each child. The chance that a child will not inherit the mutated gene is also 50 percent.
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Autosomal recessive inheritance: Two unaffected people who each carry one copy of the mutated gene for an autosomal recessive disorder (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent.
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X-linked dominant inheritance: The chance of passing on an X-linked dominant condition differs between men and women because men have one X chromosome and one Y chromosome, while women have two X chromosomes. A man passes on his Y chromosome to all of his sons and his X chromosome to all of his daughters. Therefore, the sons of a man with an X-linked dominant disorder will not be affected, but all of his daughters will inherit the condition. A woman passes on one or the other of her X chromosomes to each child. Therefore, a woman with an X-linked dominant disorder has a 50 percent chance of having an affected daughter or son with each pregnancy.
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X-linked recessive inheritance: Because of the difference in sex chromosomes, the probability of passing on an X-linked recessive disorder also differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50 percent chance of having sons who are affected and a 50 percent chance of having daughters who carry one copy of the mutated gene.
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Codominant inheritance: In codominant inheritance, each parent contributes a different version of a particular gene, and both versions influence the resulting genetic trait. The chance of developing a genetic condition with codominant inheritance, and the characteristic features of that condition, depend on which versions of the gene are passed from parents to their child.
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Mitochondrial inheritance: Mitochondria, which are the energy-producing centers inside cells, each contain a small amount of DNA. Disorders with mitochondrial inheritance result from mutations in mitochondrial DNA. Although mitochondrial
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disorders can affect both males and females, only females can pass mutations in mitochondrial DNA to their children. A woman with a disorder caused by changes in mitochondrial DNA will pass the mutation to all of her daughters and sons, but the children of a man with such a disorder will not inherit the mutation. It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not “protect” future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected. Although the chances of inheriting a genetic condition appear straightforward, factors such as a person’s family history and the results of genetic testing can sometimes modify those chances. In addition, some people with a disease-causing mutation never develop any health problems or may experience only mild symptoms of the disorder. If a disease that runs in a family does not have a clear-cut inheritance pattern, predicting the likelihood that a person will develop the condition can be particularly difficult. Estimating the chance of developing or passing on a genetic disorder can be complex. Genetics professionals can help people understand these chances and help them make informed decisions about their health. Factors that Influence the Effects of Particular Genetic Changes Reduced penetrance and variable expressivity are factors that influence the effects of particular genetic changes. These factors usually affect disorders that have an autosomal dominant pattern of inheritance, although they are occasionally seen in disorders with an autosomal recessive inheritance pattern. Reduced Penetrance Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance. Reduced penetrance often occurs with familial cancer syndromes. For example, many people with a mutation in the BRCA1 or BRCA2 gene will develop cancer during their lifetime, but some people will not. Doctors cannot predict which people with these mutations will develop cancer or when the tumors will develop. Reduced penetrance probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown. This phenomenon can make it challenging for genetics professionals to interpret a person’s family medical history and predict the risk of passing a genetic condition to future generations. Variable Expressivity Although some genetic disorders exhibit little variation, most have signs and symptoms that differ among affected individuals. Variable expressivity refers to the range of signs and
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symptoms that can occur in different people with the same genetic condition. For example, the features of Marfan syndrome vary widely— some people have only mild symptoms (such as being tall and thin with long, slender fingers), while others also experience lifethreatening complications involving the heart and blood vessels. Although the features are highly variable, most people with this disorder have a mutation in the same gene (FBN1). As with reduced penetrance, variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified. If a genetic condition has highly variable signs and symptoms, it may be challenging to diagnose. What Do Geneticists Mean by Anticipation? The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. Anticipation typically occurs with disorders that are caused by an unusual type of mutation called a trinucleotide repeat expansion. A trinucleotide repeat is a sequence of three DNA building blocks (nucleotides) that is repeated a number of times in a row. DNA segments with an abnormal number of these repeats are unstable and prone to errors during cell division. The number of repeats can change as the gene is passed from parent to child. If the number of repeats increases, it is known as a trinucleotide repeat expansion. In some cases, the trinucleotide repeat may expand until the gene stops functioning normally. This expansion causes the features of some disorders to become more severe with each successive generation. Most genetic disorders have signs and symptoms that differ among affected individuals, including affected people in the same family. Not all of these differences can be explained by anticipation. A combination of genetic, environmental, and lifestyle factors is probably responsible for the variability, although many of these factors have not been identified. Researchers study multiple generations of affected family members and consider the genetic cause of a disorder before determining that it shows anticipation. What Is Genomic Imprinting? Genomic imprinting is a factor that influences how some genetic conditions are inherited. People inherit two copies of their genes—one from their mother and one from their father. Usually both copies of each gene are active, or “turned on,” in cells. In some cases, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin: some genes are normally active only when they are inherited from a person’s father; others are active only when inherited from a person’s mother. This phenomenon is known as genomic imprinting. In genes that undergo genomic imprinting, the parent of origin is often marked, or “stamped,” on the gene during the formation of egg and sperm cells. This stamping process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. These molecules identify which copy of a gene was inherited
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from the mother and which was inherited from the father. The addition and removal of methyl groups can be used to control the activity of genes. Only a small percentage of all human genes undergo genomic imprinting. Researchers are not yet certain why some genes are imprinted and others are not. They do know that imprinted genes tend to cluster together in the same regions of chromosomes. Two major clusters of imprinted genes have been identified in humans, one on the short (p) arm of chromosome 11 (at position 11p15) and another on the long (q) arm of chromosome 15 (in the region 15q11 to 15q13). What Is Uniparental Disomy? Uniparental disomy is a factor that influences how some genetic conditions are inherited. Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development. In many cases, UPD likely has no effect on health or development. Because most genes are not imprinted, it doesn’t matter if a person inherits both copies from one parent instead of one copy from each parent. In some cases, however, it does make a difference whether a gene is inherited from a person’s mother or father. A person with UPD may lack any active copies of essential genes that undergo genomic imprinting. This loss of gene function can lead to delayed development, mental retardation, or other medical problems. Several genetic disorders can result from UPD or a disruption of normal genomic imprinting. The most well-known conditions include Prader-Willi syndrome, which is characterized by uncontrolled eating and obesity, and Angelman syndrome, which causes mental retardation and impaired speech. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15. Other conditions, such as Beckwith-Wiedemann syndrome (a disorder characterized by accelerated growth and an increased risk of cancerous tumors), are associated with abnormalities of imprinted genes on the short arm of chromosome 11. Are Chromosomal Disorders Inherited? Although it is possible to inherit some types of chromosomal abnormalities, most chromosomal disorders (such as Down syndrome and Turner syndrome) are not passed from one generation to the next. Some chromosomal conditions are caused by changes in the number of chromosomes. These changes are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra or missing chromosome in each of the body’s cells.
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Changes in chromosome structure can also cause chromosomal disorders. Some changes in chromosome structure can be inherited, while others occur as random accidents during the formation of reproductive cells or in early fetal development. Because the inheritance of these changes can be complex, people concerned about this type of chromosomal abnormality may want to talk with a genetics professional. Some cancer cells also have changes in the number or structure of their chromosomes. Because these changes occur in somatic cells (cells other than eggs and sperm), they cannot be passed from one generation to the next. Why Are Some Genetic Conditions More Common in Particular Ethnic Groups? Some genetic disorders are more likely to occur among people who trace their ancestry to a particular geographic area. People in an ethnic group often share certain versions of their genes, which have been passed down from common ancestors. If one of these shared genes contains a disease-causing mutation, a particular genetic disorder may be more frequently seen in the group. Examples of genetic conditions that are more common in particular ethnic groups are sickle cell anemia, which is more common in people of African, African-American, or Mediterranean heritage; and Tay-Sachs disease, which is more likely to occur among people of Ashkenazi (eastern and central European) Jewish or French Canadian ancestry. It is important to note, however, that these disorders can occur in any ethnic group.
Genetic Consultation This section presents information on finding and visiting a genetic counselor or other genetics professional. What Is a Genetic Consultation? A genetic consultation is a health service that provides information and support to people who have, or may be at risk for, genetic disorders. During a consultation, a genetics professional meets with an individual or family to discuss genetic risks or to diagnose, confirm, or rule out a genetic condition. Genetics professionals include medical geneticists (doctors who specialize in genetics) and genetic counselors (certified healthcare workers with experience in medical genetics and counseling). Other healthcare professionals such as nurses, psychologists, and social workers trained in genetics can also provide genetic consultations. Consultations usually take place in a doctor’s office, hospital, genetics center, or other type of medical center. These meetings are most often in-person visits with individuals or families, but they are occasionally conducted in a group or over the telephone.
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Why Might Someone Have a Genetic Consultation? Individuals or families who are concerned about an inherited condition may benefit from a genetic consultation. The reasons that a person might be referred to a genetic counselor, medical geneticist, or other genetics professional include: •
A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer.
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Two or more pregnancy losses (miscarriages), a stillbirth, or a baby who died.
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A child with a known inherited disorder, a birth defect, mental retardation, or developmental delay.
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A woman who is pregnant or plans to become pregnant at or after age 35. (Some chromosomal disorders occur more frequently in children born to older women.)
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Abnormal test results that suggest a genetic or chromosomal condition.
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An increased risk of developing or passing on a particular genetic disorder on the basis of a person’s ethnic background.
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People related by blood (for example, cousins) who plan to have children together. (A child whose parents are related may be at an increased risk of inheriting certain genetic disorders.)
A genetic consultation is also an important part of the decision-making process for genetic testing. A visit with a genetics professional may be helpful even if testing is not available for a specific condition, however. What Happens during a Genetic Consultation? A genetic consultation provides information, offers support, and addresses a patient’s specific questions and concerns. To help determine whether a condition has a genetic component, a genetics professional asks about a person’s medical history and takes a detailed family history (a record of health information about a person’s immediate and extended family). The genetics professional may also perform a physical examination and recommend appropriate tests. If a person is diagnosed with a genetic condition, the genetics professional provides information about the diagnosis, how the condition is inherited, the chance of passing the condition to future generations, and the options for testing and treatment. During a consultation, a genetics professional will: •
Interpret and communicate complex medical information.
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Help each person make informed, independent decisions about their health care and reproductive options.
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Respect each person’s individual beliefs, traditions, and feelings.
A genetics professional will NOT: •
Tell a person which decision to make.
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Advise a couple not to have children.
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Recommend that a woman continue or end a pregnancy.
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Tell someone whether to undergo testing for a genetic disorder.
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How Can I Find a Genetics Professional in My Area? To find a genetics professional in your community, you may wish to ask your doctor for a referral. If you have health insurance, you can also contact your insurance company to find a medical geneticist or genetic counselor in your area who participates in your plan. Several resources for locating a genetics professional in your community are available online: •
GeneTests from the University of Washington provides a list of genetics clinics around the United States and international genetics clinics. You can also access the list by clicking on “Clinic Directory” at the top of the GeneTests home page. Clinics can be chosen by state or country, by service, and/or by specialty. State maps can help you locate a clinic in your area. See http://www.genetests.org/.
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The National Society of Genetic Counselors offers a searchable directory of genetic counselors in the United States. You can search by location, name, area of practice/specialization, and/or ZIP Code. See http://www.nsgc.org/resourcelink.cfm.
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The National Cancer Institute provides a Cancer Genetics Services Directory, which lists professionals who provide services related to cancer genetics. You can search by type of cancer or syndrome, location, and/or provider name at the following Web site: http://cancer.gov/search/genetics_services/.
Genetic Testing This section presents information on the benefits, costs, risks, and limitations of genetic testing. What Is Genetic Testing? Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed. Genetic testing is voluntary. Because testing has both benefits and limitations, the decision about whether to be tested is a personal and complex one. A genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing.
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What Are the Types of Genetic Tests? Genetic testing can provide information about a person’s genes and chromosomes. Available types of testing include: •
Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders.
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Diagnostic testing is used to identify or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms. Diagnostic testing can be performed before birth or at any time during a person’s life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person’s choices about health care and the management of the disorder.
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Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in certain ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple’s risk of having a child with a genetic condition.
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Prenatal testing is used to detect changes in a fetus’s genes or chromosomes before birth. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple’s uncertainty or help them make decisions about a pregnancy. It cannot identify all possible inherited disorders and birth defects, however.
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Preimplantation testing, also called preimplantation genetic diagnosis (PGD), is a specialized technique that can reduce the risk of having a child with a particular genetic or chromosomal disorder. It is used to detect genetic changes in embryos that were created using assisted reproductive techniques such as in-vitro fertilization. In-vitro fertilization involves removing egg cells from a woman’s ovaries and fertilizing them with sperm cells outside the body. To perform preimplantation testing, a small number of cells are taken from these embryos and tested for certain genetic changes. Only embryos without these changes are implanted in the uterus to initiate a pregnancy.
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Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a person’s risk of developing a specific disorder and help with making decisions about medical care.
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Forensic testing uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity).
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How Is Genetic Testing Done? Once a person decides to proceed with genetic testing, a medical geneticist, primary care doctor, specialist, or nurse practitioner can order the test. Genetic testing is often done as part of a genetic consultation. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person’s doctor or genetic counselor. Newborn screening tests are done on a small blood sample, which is taken by pricking the baby’s heel. Unlike other types of genetic testing, a parent will usually only receive the result if it is positive. If the test result is positive, additional testing is needed to determine whether the baby has a genetic disorder. Before a person has a genetic test, it is important that he or she understands the testing procedure, the benefits and limitations of the test, and the possible consequences of the test results. The process of educating a person about the test and obtaining permission is called informed consent. What Is Direct-to-Consumer Genetic Testing? Traditionally, genetic tests have been available only through healthcare providers such as physicians, nurse practitioners, and genetic counselors. Healthcare providers order the appropriate test from a laboratory, collect and send the samples, and interpret the test results. Direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print advertisements, or the Internet. This form of testing, which is also known as at-home genetic testing, provides access to a person’s genetic information without necessarily involving a doctor or insurance company in the process. If a consumer chooses to purchase a genetic test directly, the test kit is mailed to the consumer instead of being ordered through a doctor’s office. The test typically involves collecting a DNA sample at home, often by swabbing the inside of the cheek, and mailing the sample back to the laboratory. In some cases, the person must visit a health clinic to have blood drawn. Consumers are notified of their results by mail or over the telephone, or the results are posted online. In some cases, a genetic counselor or other healthcare provider is available to explain the results and answer questions. The price for this type of at-home genetic testing ranges from several hundred dollars to more than a thousand dollars. The growing market for direct-to-consumer genetic testing may promote awareness of genetic diseases, allow consumers to take a more proactive role in their health care, and offer a means for people to learn about their ancestral origins. At-home genetic tests, however, have significant risks and limitations. Consumers are vulnerable to being misled by the results of unproven or invalid tests. Without guidance from a healthcare provider, they may make important decisions about treatment or prevention based on inaccurate, incomplete, or misunderstood information about their health. Consumers may also experience an invasion of genetic privacy if testing companies use their genetic information in an unauthorized way.
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Genetic testing provides only one piece of information about a person’s health—other genetic and environmental factors, lifestyle choices, and family medical history also affect a person’s risk of developing many disorders. These factors are discussed during a consultation with a doctor or genetic counselor, but in many cases are not addressed by athome genetic tests. More research is needed to fully understand the benefits and limitations of direct-to-consumer genetic testing. What Do the Results of Genetic Tests Mean? The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. Therefore, it is important for patients and their families to ask questions about the potential meaning of genetic test results both before and after the test is performed. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done. A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease (such as cancer) in the future, or suggest a need for further testing. Because family members have some genetic material in common, a positive test result may also have implications for certain blood relatives of the person undergoing testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition. A negative test result means that the laboratory did not find a change in the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result. In some cases, a negative result might not give any useful information. This type of result is called uninformative, indeterminate, inconclusive, or ambiguous. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result. What Is the Cost of Genetic Testing, and How Long Does It Take to Get the Results? The cost of genetic testing can range from under $100 to more than $2,000, depending on the nature and complexity of the test. The cost increases if more than one test is necessary or if multiple family members must be tested to obtain a meaningful result. For newborn
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screening, costs vary by state. Some states cover part of the total cost, but most charge a fee of $15 to $60 per infant. From the date that a sample is taken, it may take a few weeks to several months to receive the test results. Results for prenatal testing are usually available more quickly because time is an important consideration in making decisions about a pregnancy. The doctor or genetic counselor who orders a particular test can provide specific information about the cost and time frame associated with that test. Will Health Insurance Cover the Costs of Genetic Testing? In many cases, health insurance plans will cover the costs of genetic testing when it is recommended by a person’s doctor. Health insurance providers have different policies about which tests are covered, however. A person interested in submitting the costs of testing may wish to contact his or her insurance company beforehand to ask about coverage. Some people may choose not to use their insurance to pay for testing because the results of a genetic test can affect a person’s health insurance coverage. Instead, they may opt to pay out-of-pocket for the test. People considering genetic testing may want to find out more about their state’s privacy protection laws before they ask their insurance company to cover the costs. What Are the Benefits of Genetic Testing? Genetic testing has potential benefits whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people make informed decisions about managing their health care. For example, a negative result can eliminate the need for unnecessary checkups and screening tests in some cases. A positive result can direct a person toward available prevention, monitoring, and treatment options. Some test results can also help people make decisions about having children. Newborn screening can identify genetic disorders early in life so treatment can be started as early as possible. What Are the Risks and Limitations of Genetic Testing? The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek). The procedures used for prenatal testing carry a small but real risk of losing the pregnancy (miscarriage) because they require a sample of amniotic fluid or tissue from around the fetus. Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People may feel angry, depressed, anxious, or guilty about their results. In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern.
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Genetic testing can provide only limited information about an inherited condition. The test often can’t determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed. A genetics professional can explain in detail the benefits, risks, and limitations of a particular test. It is important that any person who is considering genetic testing understand and weigh these factors before making a decision. What Is Genetic Discrimination? Genetic discrimination occurs when people are treated differently by their employer or insurance company because they have a gene mutation that causes or increases the risk of an inherited disorder. People who undergo genetic testing may be at risk for genetic discrimination. The results of a genetic test are normally included in a person’s medical records. When a person applies for life, disability, or health insurance, the insurance company may ask to look at these records before making a decision about coverage. An employer may also have the right to look at an employee’s medical records. As a result, genetic test results could affect a person’s insurance coverage or employment. People making decisions about genetic testing should be aware that when test results are placed in their medical records, the results might not be kept private. Fear of discrimination is a common concern among people considering genetic testing. Several laws at the federal and state levels help protect people against genetic discrimination; however, genetic testing is a fast-growing field and these laws don’t cover every situation. How Does Genetic Testing in a Research Setting Differ from Clinical Genetic Testing? The main differences between clinical genetic testing and research testing are the purpose of the test and who receives the results. The goals of research testing include finding unknown genes, learning how genes work, and advancing our understanding of genetic conditions. The results of testing done as part of a research study are usually not available to patients or their healthcare providers. Clinical testing, on the other hand, is done to find out about an inherited disorder in an individual patient or family. People receive the results of a clinical test and can use them to help them make decisions about medical care or reproductive issues. It is important for people considering genetic testing to know whether the test is available on a clinical or research basis. Clinical and research testing both involve a process of informed consent in which patients learn about the testing procedure, the risks and benefits of the test, and the potential consequences of testing.
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Gene Therapy This section presents information on experimental techniques, safety, ethics, and availability of gene therapy. What Is Gene Therapy? Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including: •
Replacing a mutated gene that causes disease with a healthy copy of the gene.
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Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
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Introducing a new gene into the body to help fight a disease.
Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently only being tested for the treatment of diseases that have no other cures. How Does Gene Therapy Work? Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein. A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can’t cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome. The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient’s cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein. Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.
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A new gene is injected into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.
Is Gene Therapy Safe? Gene therapy is under study to determine whether it could be used to treat disease. Current research is evaluating the safety of gene therapy; future studies will test whether it is an effective treatment option. Several studies have already shown that this approach can have very serious health risks, such as toxicity, inflammation, and cancer. Because the techniques are relatively new, some of the risks may be unpredictable; however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research is as safe as possible. Comprehensive federal laws, regulations, and guidelines help protect people who participate in research studies (called clinical trials). The U.S. Food and Drug Administration (FDA) regulates all gene therapy products in the United States and oversees research in this area. Researchers who wish to test an approach in a clinical trial must first obtain permission from the FDA. The FDA has the authority to reject or suspend clinical trials that are suspected of being unsafe for participants. The National Institutes of Health (NIH) also plays an important role in ensuring the safety of gene therapy research. NIH provides guidelines for investigators and institutions (such as universities and hospitals) to follow when conducting clinical trials with gene therapy. These guidelines state that clinical trials at institutions receiving NIH funding for this type of research must be registered with the NIH Office of Biotechnology Activities. The protocol, or plan, for each clinical trial is then reviewed by the NIH Recombinant DNA Advisory Committee (RAC) to determine whether it raises medical, ethical, or safety issues that warrant further discussion at one of the RAC’s public meetings.
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An Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC) must approve each gene therapy clinical trial before it can be carried out. An IRB is a committee of scientific and medical advisors and consumers that reviews all research within an institution. An IBC is a group that reviews and approves an institution’s potentially hazardous research studies. Multiple levels of evaluation and oversight ensure that safety concerns are a top priority in the planning and carrying out of gene therapy research. What Are the Ethical Issues surrounding Gene Therapy? Because gene therapy involves making changes to the body’s set of basic instructions, it raises many unique ethical concerns. The ethical questions surrounding gene therapy include: •
How can “good” and “bad” uses of gene therapy be distinguished?
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Who decides which traits are normal and which constitute a disability or disorder?
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Will the high costs of gene therapy make it available only to the wealthy?
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Could the widespread use of gene therapy make society less accepting of people who are different?
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Should people be allowed to use gene therapy to enhance basic human traits such as height, intelligence, or athletic ability?
Current gene therapy research has focused on treating individuals by targeting the therapy to body cells such as bone marrow or blood cells. This type of gene therapy cannot be passed on to a person’s children. Gene therapy could be targeted to egg and sperm cells (germ cells), however, which would allow the inserted gene to be passed on to future generations. This approach is known as germline gene therapy. The idea of germline gene therapy is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known. Because people who would be affected by germline gene therapy are not yet born, they can’t choose whether to have the treatment. Because of these ethical concerns, the U.S. Government does not allow federal funds to be used for research on germline gene therapy in people. Is Gene Therapy Available to Treat My Disorder? Gene therapy is currently available only in a research setting. The U.S. Food and Drug Administration (FDA) has not yet approved any gene therapy products for sale in the United States. Hundreds of research studies (clinical trials) are under way to test gene therapy as a treatment for genetic conditions, cancer, and HIV/AIDS. If you are interested in participating in a clinical trial, talk with your doctor or a genetics professional about how to participate. You can also search for clinical trials online. ClinicalTrials.gov, a service of the National Institutes of Health, provides easy access to information on clinical trials. You can search for
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specific trials or browse by condition or trial sponsor. You may wish to refer to a list of gene therapy trials that are accepting (or will accept) patients.
The Human Genome Project and Genomic Research This section presents information on the goals, accomplishments, and next steps in understanding the human genome. What Is a Genome? A genome is an organism’s complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus. What Was the Human Genome Project and Why Has It Been Important? The Human Genome Project was an international research effort to determine the sequence of the human genome and identify the genes that it contains. The Project was coordinated by the National Institutes of Health and the U.S. Department of Energy. Additional contributors included universities across the United States and international partners in the United Kingdom, France, Germany, Japan, and China. The Human Genome Project formally began in 1990 and was completed in 2003, 2 years ahead of its original schedule. The work of the Human Genome Project has allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life sciences. What Were the Goals of the Human Genome Project? The main goals of the Human Genome Project were to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The Project also aimed to sequence the genomes of several other organisms that are important to medical research, such as the mouse and the fruit fly. In addition to sequencing DNA, the Human Genome Project sought to develop new tools to obtain and analyze the data and to make this information widely available. Also, because advances in genetics have consequences for individuals and society, the Human Genome Project committed to exploring the consequences of genomic research through its Ethical, Legal, and Social Implications (ELSI) program. What Did the Human Genome Project Accomplish? In April 2003, researchers announced that the Human Genome Project had completed a high-quality sequence of essentially the entire human genome. This sequence closed the
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gaps from a working draft of the genome, which was published in 2001. It also identified the locations of many human genes and provided information about their structure and organization. The Project made the sequence of the human genome and tools to analyze the data freely available via the Internet. In addition to the human genome, the Human Genome Project sequenced the genomes of several other organisms, including brewers’ yeast, the roundworm, and the fruit fly. In 2002, researchers announced that they had also completed a working draft of the mouse genome. By studying the similarities and differences between human genes and those of other organisms, researchers can discover the functions of particular genes and identify which genes are critical for life. The Project’s Ethical, Legal, and Social Implications (ELSI) program became the world’s largest bioethics program and a model for other ELSI programs worldwide. What Were Some of the Ethical, Legal, and Social Implications Addressed by the Human Genome Project? The Ethical, Legal, and Social Implications (ELSI) program was founded in 1990 as an integral part of the Human Genome Project. The mission of the ELSI program was to identify and address issues raised by genomic research that would affect individuals, families, and society. A percentage of the Human Genome Project budget at the National Institutes of Health and the U.S. Department of Energy was devoted to ELSI research. The ELSI program focused on the possible consequences of genomic research in four main areas: •
Privacy and fairness in the use of genetic information, including the potential for genetic discrimination in employment and insurance.
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The integration of new genetic technologies, such as genetic testing, into the practice of clinical medicine.
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Ethical issues surrounding the design and conduct of genetic research with people, including the process of informed consent.
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The education of healthcare professionals, policy makers, students, and the public about genetics and the complex issues that result from genomic research. What Are the Next Steps in Genomic Research?
Discovering the sequence of the human genome was only the first step in understanding how the instructions coded in DNA lead to a functioning human being. The next stage of genomic research will begin to derive meaningful knowledge from the DNA sequence. Research studies that build on the work of the Human Genome Project are under way worldwide. The objectives of continued genomic research include the following: •
Determine the function of genes and the elements that regulate genes throughout the genome.
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Find variations in the DNA sequence among people and determine their significance. These variations may one day provide information about a person’s disease risk and response to certain medications.
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Discover the 3-dimensional structures of proteins and identify their functions.
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Explore how DNA and proteins interact with one another and with the environment to create complex living systems.
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Develop and apply genome-based strategies for the early detection, diagnosis, and treatment of disease.
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Sequence the genomes of other organisms, such as the rat, cow, and chimpanzee, in order to compare similar genes between species.
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Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently.
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Continue to explore the ethical, legal, and social issues raised by genomic research. What Is Pharmacogenomics?
Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup. Many drugs that are currently available are “one size fits all,” but they don’t work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body’s response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions. The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.
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APPENDIX B. 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 Institute12: •
National Institutes of Health (NIH); guidelines consolidated across agencies available at http://health.nih.gov/
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/Publications/FactSheets.htm
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancertopics/pdq
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/health/
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/HealthInformation/Publications/
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/Publications/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidcr.nih.gov/HealthInformation/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/healthinformation/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Biomedical Imaging and Bioengineering; general information at http://www.nibib.nih.gov/HealthEdu
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 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
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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).
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citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine14: •
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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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/index.html
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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/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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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
14
See http://www.nlm.nih.gov/databases/index.html.
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The NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type Crohn 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 21545 186 72 23 7 21833
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by Crohn disease (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 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 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 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.22 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: •
MD Consult: Access to electronic clinical resources, see http://www.mdconsult.com/.
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Medical Matrix: Lists over 6000 medical Web sites and links to over 1.5 million documents with clinical content, see http://www.medmatrix.org/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
21
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. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX C. 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 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 This section directs you to sources which either publish fact sheets or can help you find additional guidelines on topics related to Crohn 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 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 disease:
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Alzheimer's Disease http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html Behcet's Syndrome http://www.nlm.nih.gov/medlineplus/behcetssyndrome.html Colonic Diseases http://www.nlm.nih.gov/medlineplus/colonicdiseases.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/tutorials/crohnsdisease/htm/index.htm Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseases.html Foot Injuries and Disorders http://www.nlm.nih.gov/medlineplus/footinjuriesanddisorders.html Gastroenteritis http://www.nlm.nih.gov/medlineplus/gastroenteritis.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.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. 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: •
Crohn's Disease Summary: Provides general information on what Crohn's disease is and how it develops. Source: digestive.niddk.nih.gov http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/
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DAN Divers Alert Network : Crohns Disease and Diving Summary: FAQs Crohns Disease and Diving. Q: I have a newstudent with a history of Crohn's disease who has had a colostomy for 20 years. Source: www.diversalertnetwork.org http://www.diversalertnetwork.org/medical/faq/faq.asp?faqid=58
•
HONselect - Crohn Disease Summary: English: Crohn Disease, - Colitis, Granulomatous - Enteritis, Regional - Ileitis, Terminal - Ileocolitis. Source: www.hon.ch http://www.hon.ch/HONselect/RareDiseases/C06.405.205.731.500.html
•
Inflammatory Bowel Disease Summary: This allows her to "see" the lining of the whole colon and check for signs of UC. What is Crohn's disease (CD)? What are the symptoms of Crohn's disease (CD)? Source: www.womenshealth.gov http://www.womenshealth.gov/faq/ibd.htm
•
MedlinePlus: Crohn's Disease Summary: PDF. Select services and providers for Crohn's Disease in your area. View slideshow on: Colonoscopy. Source: www.nlm.nih.gov http://www.nlm.nih.gov/medlineplus/crohnsdisease.html
•
MedlinePlus: Ulcerative Colitis Summary: Coping; Crohn's Disease and Ulcerative Colitis: Emotional Factors (Crohn's& Colitis Foundation of America) - Links to PDF. Source: www.nlm.nih.gov http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html
•
Melkersson-Rosenthal Syndrome Information Page: National Institute. Summary: It can be symptomatic of Crohn's disease or sarcoidosis. Follow-up care shouldexclude the development of Crohn's disease or sarcoidosis. Source: www.ninds.nih.gov http://www.ninds.nih.gov/disorders/melkersson/melkersson.htm
•
Smoking and Your Digestive System Source: digestive.niddk.nih.gov http://digestive.niddk.nih.gov/ddiseases/pubs/smoking/
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Ulcerative Colitis Summary:
[email protected] Internet: www.ccfa.org. Reach Out for Youth With Ileitis and Colitis Inc. 84 Northgate Circle Melville, NY 11747 Phone. Source: digestive.niddk.nih.gov http://digestive.niddk.nih.gov/ddiseases/pubs/colitis/
•
What is Fecal Incontinence? Summary: The more serious causes include ulcerative colitis (when blood is usually presentin the stools), regional ileitis (Crohn’s disease). Source: www.nafc.org http://www.nafc.org/index.asp?PageName=FecalExpandedTreatment
•
Zigawhat! Tips Just For You Summary: Teens With Crohn's Disease This terrific site is written and maintained by teens with Crohn's Disease. Source: www.nichcy.org http://www.nichcy.org/kids/tips.htm 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 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://health.nih.gov/index.asp. Under Search Health Topics, type Crohn disease (or synonyms) into the search box, and click Search. 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: •
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
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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://www.webmd.com/diseases_and_conditions/default.htm
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Crohn disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Crohn 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 disease. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://sis.nlm.nih.gov/dirline.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. Simply type in Crohn 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://healthhotlines.nlm.nih.gov/. 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 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 disease (or a synonym) into the search box, and click Submit Query.
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Resources for Patients and Families The following are organizations that provide support and advocacy for patient with genetic conditions and their families23: •
Genetic Alliance: http://geneticalliance.org
•
Genetic and Rare Diseases Information Center: http://rarediseases.info.nih.gov/html/resources/info_cntr.html
•
Madisons Foundation: http://www.madisonsfoundation.org/
•
March of Dimes: http://www.marchofdimes.com
•
National Organization for Rare Disorders (NORD): http://www.rarediseases.org/ For More Information on Genetics
The following publications offer detailed information for patients about the science of genetics: •
What Is a Genome?: http://www.ncbi.nlm.nih.gov/About/primer/genetics_genome.html
•
A Science Called Genetics: http://publications.nigms.nih.gov/genetics/science.html
•
Genetic Mapping: http://www.genome.gov/10000715
23
Adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/ghr/resource/patients.
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
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/archive//20040831/nichsr/ta101/ta10108.html
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 disease: •
Basic Guidelines for Crohn Disease Crohn's disease (regional enteritis) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000249.htm
•
Signs & Symptoms for Crohn 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
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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 Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.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 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 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 Tenesmus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003131.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •
Diagnostics and Tests for Crohn Disease Albumin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003480.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
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Endoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003338.htm Fecal fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003588.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 •
Nutrition for Crohn Disease Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm Vitamins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002399.htm
•
Background Topics for Crohn Disease Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.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
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•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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CROHN DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [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] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex
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characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] 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] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] 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 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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] 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] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the
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secretory granules of intestinal paneth cells. [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] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] 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] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy
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(symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [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] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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-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-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] 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] Antiviral: Destroying viruses or suppressing their replication. [EU] Antrectomy: An operation to remove the upper portion of the stomach, called the antrum. This operation helps reduce the amount of stomach acid. It is used when a person has complications from ulcers. [NIH]
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Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apheresis: Components plateletpheresis. [NIH]
being
separated
out,
as
leukapheresis,
plasmapheresis,
Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] 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] Arthropathy: Any joint disease. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] 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]
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Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] 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] 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] Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Biliopancreatic Diversion: A surgical procedure which diverts pancreatobiliary secretions via the duodenum and the jejunum into the colon, the remaining small intestine being anastomosed to the stomach after antrectomy. The procedure produces less diarrhea than does jejunoileal bypass. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving
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chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [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 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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [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] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small
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amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] 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] Bronchial: Pertaining to one or more bronchi. [EU] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] 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] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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] 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] 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] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic
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hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are
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joined and by which the chromosome is attached to the spindle during cell division. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [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] 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] 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] Chromosome Fragility: Susceptibility of chromosomes to breakage and translocation or other aberrations. Chromosome fragile sites are regions that show up in karyotypes as a gap (uncondensed stretch) on the chromatid arm. They are associated with chromosome break sites and other aberrations. A fragile site on the X chromosome is associated with fragile X syndrome. Fragile sites are designated by the letters "FRA" followed by the designation for the specific chromosome and a letter which refers to the different fragile sites on a chromosome (e.g. FRAXA). [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic 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 phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient.
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[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] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [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] 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] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] 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] Colostomy: An opening into the colon from the outside of the body. A colostomy provides a new path for waste material to leave the body after part of the colon has been removed. [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.
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Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of
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clear thinking, and perceptual disorientation. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] 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 Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] 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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH]
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Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is
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multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] 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]
Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [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] 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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] 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] 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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues
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react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [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] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] 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 Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] 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] 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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the
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chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] 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-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enema: The injection of a liquid through the anus into the large bowel. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [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] 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 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] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU]
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Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excrete: To get rid of waste from the body. [NIH] 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] Eye Color: Color of the iris. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [NIH]
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Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flagellin: A protein with a molecular weight of 40,000 isolated from bacterial flagella. At appropriate pH and salt concentration, three flagellin monomers can spontaneously reaggregate to form structures which appear identical to intact flagella. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fold: A plication or doubling of various parts of the body. [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] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] 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
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in the gallbladder. [NIH] Gamma-Endorphin: An endogenous opioid peptide derived from the pro-opiomelanocortin precursor peptide. It differs from alpha-endorphin by one amino acid. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastritis: Inflammation of the stomach. [EU] 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] 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] Gastrointestinal: Refers to the stomach and intestines. [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] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH]
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Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germfree: Free from all living micro-organisms. [NIH] Germ-free: Free of bacteria, disease-causing viruses, and other organisms that can cause infection. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [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] 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] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body.
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[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] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [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] Hair Color: Color of hair or fur. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [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] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH]
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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] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] 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] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein
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hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydronephrosis: Abnormal enlargement of a kidney, which may be caused by blockage of the ureter (such as by a kidney stone) or chronic kidney disease that prevents urine from draining into the bladder. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] 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] Hypnotic: A drug that acts to induce sleep. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] 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] 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] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] 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] Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment
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of cancer. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] 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]
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]
Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Ingestion: Taking into the body by mouth [NIH]
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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] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] 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 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-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] 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] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH]
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Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] 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]
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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Jejunoileal Bypass: A surgical procedure consisting of the anastomosis of the proximal part of the jejunum to the distal portion of the ileum, so as to bypass the nutrient-absorptive segment of the small intestine, to treat morbid obesity. [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] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] Keratitis: Inflammation of the cornea. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in
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blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [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] 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] Lesion: An area of abnormal tissue change. [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]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] 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] 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] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] 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]
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Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte 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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] 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
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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] 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]
Mammography: Radiographic examination of the breast. [NIH] Mannans: Polysaccharides consisting of mannose units. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] 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] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH]
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Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] 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] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] 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] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells
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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] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [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]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myelodysplastic Syndromes: Conditions in which the bone marrow shows qualitative and quantitative changes suggestive of a preleukemic process, but having a chronic course that does not necessarily terminate as acute leukemia. [NIH] Myelotoxic: 1. Destructive to bone marrow. 2. Arising from diseased bone marrow. [EU]
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Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] 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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephropathy: Disease of the kidneys. [EU] 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] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [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] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood
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cell. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] 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] 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 Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [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,
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waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic disc: The circular area (disc) where the optic nerve connects to the retina. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [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] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH]
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Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [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] Pancreatic: Having to do with the pancreas. [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] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Paratuberculosis: An infectious disease caused by Mycobacterium paratuberculosis. Characteristics include chronic debilitation and weight loss. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Paternity: Establishing the father relationship of a man and a child. [NIH] Pathogen: Any disease-producing microorganism. [EU] 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 Education: The teaching or training of patients concerning their own health needs.
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[NIH]
PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perianal: Located around the anus. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [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] Peroral: Performed through or administered through the mouth. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of
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mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] 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] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [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] 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] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors,
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precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet 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] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]
Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [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]
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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] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [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 endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH]
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Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] 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] 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 Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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]
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Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psoas Abscess: Abscess of the psoas muscle resulting usually from disease of the lumbar vertebrae, with the pus descending into the muscle sheath. The infection is most commonly tuberculous or staphylococcal. [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] 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] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] 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]
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Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from 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] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [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] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] 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]
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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] Relapse: The return of signs and symptoms of cancer after a period of improvement. [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] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restitution: The restoration to a normal state. [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] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrobulbar: Behind the pons. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH]
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Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Ruminants: A suborder of the order Artiodactyla whose members have the distinguishing feature of a four-chambered stomach. Horns or antlers are usually present, at least in males. [NIH]
Sacroiliac Joint: The immovable joint formed by the lateral surfaces of the sacrum and ilium. [NIH] Saimiri: A genus of the family Cebidae consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] 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] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH]
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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] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [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]
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] 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
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differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [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 Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Soybean Oil: Oil from soybean or soybean plant. [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,
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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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Standardize: To compare with or conform to a standard; to establish standards. [EU] 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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] 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] Stoma: A surgically created opening from an area inside the body to the outside. [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] 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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [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] 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.
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[NIH]
Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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] 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] 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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [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] Thermogenesis: The generation of heat in order to maintain body temperature. The uncoupled oxidation of fatty acids contained within brown adipose tissue and shivering are examples of thermogenesis in mammals. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH]
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Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, 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] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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]
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Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trinucleotide Repeat Expansion: DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats. [NIH] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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] 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] 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] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
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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] 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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] 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] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the
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opening to the vagina. [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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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] Zygote: The fertilized ovum. [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]
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INDEX 3 3-dimensional, 103, 134, 150 A Abdomen, 5, 150, 157, 160, 171, 176, 177, 186, 197, 201 Abdominal Pain, 4, 13, 150, 169, 200 Abscess, 58, 91, 150, 152, 191 Acceptor, 150, 185 Acetylcholine, 150, 182, 183 Acute leukemia, 150, 181, 198 Acute renal, 150, 172 Adaptability, 150, 158 Adenine, 97, 150, 191 Adenocarcinoma, 31, 54, 64, 150 Adenosine, 98, 150, 187 Adenosine Triphosphate, 98, 150, 187 Adenovirus, 130, 150 Adipose Tissue, 75, 78, 150, 198 Adjuvant, 74, 150 Adolescence, 38, 150 Adoptive Transfer, 18, 151 Adrenal Cortex, 151, 162, 189 Adverse Effect, 151, 195 Aerobic, 151, 180 Afferent, 151, 184 Agar, 151, 163 Alanine, 66, 151 Albumin, 23, 147, 151, 187 Alendronate, 73, 151 Algorithms, 12, 151, 156 Alimentary, 78, 79, 151, 166 Alkaline, 151, 152, 155, 157 Alleles, 15, 20, 99, 116, 151, 177 Allergic Rhinitis, 151, 157 Allogeneic, 9, 151, 171 Alpha-1, 112, 116, 151 Alpha-Defensins, 151, 163 Alternative medicine, 152 Amino Acid Sequence, 152, 153, 190 Amino Acids, 99, 103, 109, 152, 160, 186, 188, 190, 194, 199, 200 Ammonia, 152, 170 Amnion, 152 Amniotic Fluid, 125, 127, 152 Amplification, 26, 152 Ampulla, 152, 166 Anaesthesia, 152, 174 Anal, 11, 67, 73, 152 Anal Fistula, 73, 152
Analog, 152, 180 Analogous, 152, 188, 199 Anastomosis, 56, 66, 152, 176 Anatomical, 152, 159, 174, 194 Androgens, 151, 152, 162 Anemia, 4, 51, 64, 111, 112, 115, 116, 121, 152 Aneuploidy, 110, 152 Anions, 151, 153, 176 Anorectal, 32, 55, 153 Anorexia, 153, 169, 200 Antiallergic, 153, 162 Antibacterial, 153, 196 Antibiotic, 18, 153, 168, 196 Antibodies, 13, 14, 16, 79, 104, 153, 154, 173, 187 Anticoagulant, 153, 190 Antigen, 17, 18, 20, 28, 34, 153, 161, 164, 172, 173, 174, 179, 195 Antigen-presenting cell, 153, 164 Anti-inflammatory, 32, 61, 153, 162, 170, 189 Anti-Inflammatory Agents, 153, 162 Antimetabolite, 153, 198 Antimicrobial, 24, 153, 163 Antineoplastic, 153, 162, 198 Antioxidant, 12, 29, 53, 75, 153 Antiviral, 153, 175, 186 Antrectomy, 153, 155 Anuria, 154, 176 Anus, 152, 153, 154, 157, 160, 166, 186, 192 Anxiety, 30, 154 Apheresis, 59, 78, 154 Apoptosis, 34, 98, 107, 154, 158 Aqueous, 154, 155, 163 Archaea, 154, 180 Arginine, 82, 154, 172, 183 Arterial, 154, 173, 190 Arteries, 154, 156, 162 Arterioles, 62, 154, 156, 157, 180 Arteritis, 10, 48, 154 Artery, 31, 63, 154, 185, 191 Arthralgia, 79, 154 Arthropathy, 45, 154 Aseptic, 154, 184 Asymptomatic, 154, 185 Attenuation, 16, 39, 63, 154 Atypical, 32, 33, 89, 120, 154 Autoantibodies, 20, 154
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Autoantigens, 154 Autodigestion, 154, 185 Autoimmune disease, 15, 24, 154, 155, 181 Autoimmunity, 21, 155 Autologous, 47, 53, 155, 171 Autologous bone marrow transplantation, 155, 171 B Bacteria, 4, 7, 8, 18, 20, 22, 96, 104, 108, 153, 154, 155, 166, 167, 168, 170, 176, 180, 195, 196, 199, 201 Bacterium, 155, 172 Barbiturate, 155, 198 Barium, 36, 147, 155 Base, 9, 97, 98, 101, 103, 107, 108, 109, 132, 150, 155, 163, 164, 168, 176, 177, 200 Base Sequence, 108, 155, 168 Basement Membrane, 48, 155, 167, 177 Beta-Defensins, 155, 163 Bewilderment, 155, 161 Bilateral, 34, 59, 155 Bile, 155, 159, 168, 172, 177, 197 Bile duct, 155, 159 Biliary, 155, 185 Biliary Tract, 155, 185 Biliopancreatic Diversion, 38, 155 Bilirubin, 151, 155 Binding Sites, 62, 155 Bioavailable, 23, 155 Biochemical, 17, 112, 151, 153, 155, 176, 190 Biological response modifier, 156, 175 Biological therapy, 156, 171 Biopsy, 62, 64, 148, 156, 186 Biotechnology, 5, 29, 103, 130, 132, 137, 156 Bladder, 4, 34, 156, 173, 181, 201 Blast phase, 156, 159 Blastocyst, 156, 161 Blood Coagulation, 156, 157, 199 Blood Glucose, 156, 171, 175 Blood pressure, 115, 156, 157, 173, 181 Blood vessel, 119, 156, 157, 159, 166, 172, 178, 179, 196, 197, 199, 201 Blot, 12, 156 Body Composition, 28, 71, 156 Body Fluids, 156, 165, 168, 183 Bone Density, 28, 156 Bone Marrow, 18, 53, 131, 150, 155, 156, 159, 167, 169, 171, 173, 178, 181, 197 Bone scan, 156, 194
Bowel, 13, 32, 33, 35, 38, 41, 43, 45, 54, 56, 57, 60, 64, 70, 73, 74, 75, 76, 78, 79, 81, 87, 88, 90, 142, 148, 152, 157, 164, 166, 174, 176, 186, 197, 200 Bowel Movement, 157, 164, 197 Bradykinin, 157, 183, 188 Bronchial, 157 Bronchopulmonary, 41, 157 Buccal, 35, 125, 127, 157, 178 Budesonide, 29, 57, 157 C Cachexia, 35, 157 Calcium, 18, 157, 160, 196 Capillary, 157, 201 Capsules, 157, 165 Carbohydrate, 157, 162, 188 Carcinogenic, 157, 175, 190, 197 Carcinoma, 35, 45, 73, 157 Cardiac, 157, 197 Cardiovascular, 134, 157 Cardiovascular disease, 134, 157 Carotene, 157, 193 Case report, 32, 36, 37, 41, 52, 54, 158 Case-Control Studies, 22, 158 Caspase, 7, 158 Catheters, 158, 168 Causal, 28, 158, 175, 198 Causality, 25, 158 Cause of Death, 158, 163 Cecum, 158, 177 Cell Cycle, 106, 107, 158 Cell Death, 107, 154, 158, 182 Cell Differentiation, 158, 196 Cell Division, 99, 106, 107, 119, 120, 155, 158, 159, 171, 179, 180, 187, 195 Cell proliferation, 158, 175, 196 Cell Respiration, 158, 180 Cell Survival, 158, 171 Cell Transplantation, 9, 53, 158, 171 Central Nervous System, 37, 150, 151, 158, 169, 170, 181, 184 Centromere, 99, 102, 158 Cerebral, 51, 159, 167 Cerebrovascular, 157, 159 Cerebrum, 159 Cheilitis, 47, 159 Chemotherapy, 74, 159 Chin, 159, 179 Chlorophyll, 159, 166, 168 Cholangitis, 38, 47, 159 Cholesterol, 98, 155, 159, 162, 197 Chromatin, 154, 159, 178, 183
Index 205
Chromosomal, 107, 109, 110, 120, 121, 122, 124, 152, 159, 172, 181 Chromosome Fragility, 159, 200 Chronic Disease, 157, 159, 177 Chronic myelogenous leukemia, 156, 159, 178 Chronic phase, 24, 159 Cirrhosis, 159, 171 CIS, 159, 169, 170, 193 Clinical Medicine, 133, 159, 189 Clinical trial, 11, 19, 28, 130, 131, 134, 137, 160, 162, 165, 186, 191, 192 Cloning, 156, 160 Cluster Analysis, 87, 160 Codon, 104, 160 Cofactor, 160, 190, 199 Colectomy, 53, 160 Colitis, 4, 6, 7, 12, 13, 34, 56, 61, 64, 75, 81, 87, 88, 89, 90, 91, 141, 142, 143, 160 Collagen, 155, 160, 188 Colloidal, 151, 160 Colon, 3, 4, 18, 25, 29, 35, 44, 80, 81, 88, 113, 142, 155, 160, 174, 177, 195, 200 Colonoscopy, 88, 115, 142, 147, 160 Colorectal, 62, 80, 160 Colostomy, 142, 160 Complement, 160, 161, 176, 179, 187 Complementary medicine, 72, 161 Complete remission, 161, 193 Computational Biology, 137, 161 Computed tomography, 36, 68, 156, 161, 194 Computerized axial tomography, 161, 194 Computerized tomography, 161 Concentric, 161, 183 Conception, 106, 161, 168, 196 Cones, 161, 193 Confusion, 113, 161, 165, 200, 201 Connective Tissue, 156, 160, 162, 168, 169, 178, 198 Consciousness, 162, 164 Constriction, 99, 102, 162 Consultation, 121, 122, 125, 126, 162 Contraindications, ii, 162 Contrast Sensitivity, 162, 184 Control group, 162, 189 Controlled study, 70, 73, 80, 162 Cornea, 37, 162, 176, 197 Coronary, 157, 162 Coronary heart disease, 157, 162 Cortex, 82, 162, 167 Corticosteroid, 20, 23, 162, 189
Cortisol, 151, 162 Cortisone, 162, 189 Cranial, 10, 163, 182, 184 Crowding, 23, 163 Culture Media, 21, 151, 163 Curative, 163, 198 Cutaneous, 39, 41, 46, 163, 178 Cyclic, 163, 171, 183, 190 Cysteine, 163 Cytochrome, 163, 185 Cytokine, 16, 19, 20, 24, 46, 163, 175, 198 Cytoplasm, 96, 97, 98, 104, 154, 163, 166, 171, 178, 183, 194 Cytosine, 97, 163, 192 Cytotoxic, 163, 196 D Data Collection, 27, 163 De novo, 107, 163 Death Certificates, 115, 163 Defensins, 24, 76, 151, 155, 163 Deletion, 109, 154, 163 Dementia, 110, 163 Dendrites, 164 Dendritic, 7, 16, 24, 164 Dendritic cell, 7, 16, 24, 164 Deoxyribonucleic, 97, 164, 193 Deoxyribonucleic acid, 97, 164, 193 Deoxyribonucleotides, 164 Depolarization, 164, 196 Deuterium, 23, 164, 173 Developed Countries, 26, 164 Diabetes Mellitus, 164, 171 Diagnostic procedure, 86, 164 Diarrhea, 4, 13, 40, 50, 81, 147, 155, 164 Diarrhoea, 164, 169 Digestion, 73, 151, 155, 157, 164, 176, 177, 197, 201 Digestive system, 3, 4, 7, 164, 169 Digestive tract, 4, 8, 164, 196 Diploid, 152, 164, 181, 187, 200 Direct, iii, 27, 40, 92, 125, 126, 127, 159, 164, 192 Discrete, 164, 190 Discrimination, 127, 128, 133, 164 Disease Progression, 27, 164 Disease Susceptibility, 25, 56, 164 Disorientation, 162, 165 Distal, 165, 176, 186 Diverticulum, 51, 165 Dosage Forms, 88, 165 Dose-dependent, 16, 165 Double-blind, 28, 66, 72, 79, 165
206
Crohn Disease
Drug Interactions, 93, 165 Drug Tolerance, 165, 199 Duct, 152, 165, 194, 197 Duodenum, 155, 165, 166, 176, 197 Dyes, 165, 183 Dysplasia, 64, 165 E Edema, 64, 165, 200 Effector, 14, 150, 160, 165 Effector cell, 14, 165 Efficacy, 20, 28, 30, 41, 165 Electrolyte, 162, 165, 168, 177, 180, 183, 200 Electrons, 153, 155, 165, 176, 185, 192 Embolism, 51, 166 Embryo, 106, 107, 108, 116, 152, 156, 158, 166, 174, 188 Endogenous, 13, 154, 166, 169, 184, 199 Endorphin, 166, 169 Endoscope, 166 Endoscopic, 13, 19, 39, 44, 53, 63, 160, 166, 195 Endoscopy, 13, 19, 26, 33, 38, 59, 148, 166 Endothelium, 166, 183 Endothelium-derived, 166, 183 Endotoxin, 166, 200 Enema, 147, 166 Enkephalin, 13, 166, 190 Enteral Nutrition, 75, 77, 79, 166 Enteric bacteria, 22, 166 Enteritis, 18, 20, 142, 166 Enterocolitis, 166 Enteroscopy, 60, 166 Environmental Health, 136, 137, 166 Enzymatic, 20, 157, 158, 161, 166, 193 Enzyme, 20, 98, 104, 158, 165, 166, 169, 170, 171, 180, 186, 187, 190, 195, 199, 201, 202 Eosinophil, 49, 166 Eosinophilic, 166 Epidemiological, 12, 166 Epithelial, 24, 77, 150, 155, 167, 177 Epithelial Cells, 24, 77, 155, 167, 177 Epithelium, 35, 88, 155, 166, 167, 176 Epitope, 15, 167 Erythrocytes, 152, 156, 167, 185, 187, 192 Erythropoietin, 51, 167 Escalation, 20, 167 Esophagitis, 54, 167 Esophagus, 164, 167, 169, 197 Ethnic Groups, 121, 124, 167 Eukaryotic Cells, 167, 174, 184
Evoke, 167, 197 Excrete, 154, 167, 176 Exogenous, 166, 167 Extensor, 167, 191 Extracellular, 162, 167, 184 Extracellular Matrix, 162, 167, 184 Eye Color, 108, 167 Eye Infections, 150, 167 F Family Planning, 137, 167 Fat, 148, 150, 156, 157, 162, 167, 177, 181, 184, 188, 196 Fathers, 116, 167 Fatty acids, 77, 78, 151, 167, 190, 198 Feasibility Studies, 59, 167 Feces, 168, 197 Fetus, 124, 125, 127, 131, 167, 168, 189, 197, 201 Fibrosis, 23, 108, 111, 115, 116, 168, 194 Fistula, 42, 50, 61, 62, 168 Flagellin, 34, 168 Flatus, 168, 169 Fluid Therapy, 168, 183 Fluorescence, 21, 22, 168 Fold, 16, 168, 179 Forearm, 156, 168 Frameshift, 10, 22, 109, 168 Frameshift Mutation, 10, 22, 109, 168 Free Radicals, 153, 168 Fungemia, 53, 168 Fungus, 53, 168 G Gadolinium, 55, 168 Gallbladder, 45, 150, 155, 164, 168, 169 Gamma-Endorphin, 169 Ganglia, 150, 169, 182 Gangrene, 44, 169 Gas, 42, 152, 168, 169, 173, 183 Gastric, 45, 62, 79, 154, 165, 169, 180 Gastric Acid, 169, 180 Gastrin, 70, 169, 172 Gastritis, 45, 81, 169 Gastroenteritis, 141, 169 Gastrointestinal, 13, 16, 17, 21, 26, 47, 53, 55, 70, 147, 157, 166, 169, 197 Gastrointestinal tract, 16, 17, 21, 26, 47, 53, 169 Gastrostomy, 166, 169 Gene, 3, 4, 6, 7, 8, 9, 10, 12, 14, 15, 22, 25, 26, 29, 30, 46, 56, 59, 60, 63, 65, 68, 87, 99, 101, 102, 103, 104, 105, 107, 108, 109, 111, 112, 113, 115, 116, 117, 118, 119,
Index 207
120, 124, 126, 127, 128, 129, 130, 131, 132, 150, 151, 156, 169, 170, 172, 175, 195 Gene Expression, 12, 104, 105, 169 Gene Products, rev, 169, 170 Gene Therapy, 65, 129, 130, 131, 132, 150, 169 Genes, env, 115, 170 Genetic Markers, 25, 170 Genetic testing, 27, 46, 118, 122, 123, 124, 125, 126, 127, 128, 133, 170 Genital, 32, 46, 170, 201 Genomics, 46, 134, 170 Genotype, 11, 15, 170, 187 Germ Cells, 107, 131, 170, 179, 185, 196 Germfree, 18, 170 Germ-free, 18, 170 Germline mutation, 107, 170, 172 Gland, 151, 162, 170, 178, 185, 187, 195, 197, 199 Glucocorticoid, 157, 170, 189 Glucose, 156, 164, 170, 171, 175, 194 Glutamic Acid, 170, 182 Glutamine, 77, 83, 170 Glutathione Peroxidase, 170, 195 Glycoprotein, 167, 170, 177, 199, 200 Gonadal, 170, 197 Governing Board, 170, 189 Gp120, 170, 186 Graft, 9, 10, 171, 174, 178 Graft Rejection, 171, 174, 178 Graft-versus-host disease, 9, 10, 171 Granule, 171, 194 Granulocytes, 171, 177, 196, 202 Groin, 34, 171 Growth factors, 77, 171 Guanine, 97, 171, 191 Guanylate Cyclase, 171, 183 H Hair Color, 108, 171 Haplotypes, 14, 15, 171 Heart attack, 157, 171 Hematopoietic Stem Cell Transplantation, 47, 171 Hemochromatosis, 124, 171 Hemodialysis, 171, 176, 177 Hemoglobin, 98, 152, 167, 171, 177 Hemoglobinopathies, 169, 171 Hemolytic, 64, 172 Hemophilia, 116, 172 Hemorrhage, 172, 197 Hepatic, 151, 172, 177 Hepatotoxic, 20, 172
Hereditary, 96, 97, 107, 116, 122, 170, 172, 193 Hereditary mutation, 107, 170, 172 Heredity, 99, 169, 170, 172 Heterogeneity, 11, 12, 172 Histology, 13, 19, 172 Histones, 99, 159, 172 Homeostasis, 16, 172 Homogeneous, 14, 172, 186 Homologous, 17, 151, 169, 172, 195, 198 Hormonal, 162, 172 Hormone, 28, 41, 55, 69, 104, 162, 167, 169, 172, 175, 189, 193, 195, 199 Hormone therapy, 41, 172 Humoral, 21, 171, 172 Humour, 172 Hybrid, 67, 172 Hybridization, 12, 28, 87, 172 Hydrogen, 23, 150, 155, 157, 164, 170, 173, 181, 183, 185, 186, 191 Hydrolysis, 173, 187, 188, 190 Hydronephrosis, 52, 173 Hyperreflexia, 173, 198 Hypersensitivity, 166, 173, 193 Hypertension, 157, 173, 200 Hypnotic, 155, 173, 198 Hypothalamus, 166, 173, 187, 190 I Idiopathic, 21, 27, 40, 173, 191, 194 Ileal, 24, 61, 67, 173 Ileitis, 18, 37, 90, 143, 173 Ileostomy, 53, 57, 63, 173 Ileum, 3, 4, 8, 18, 24, 31, 43, 56, 60, 65, 78, 88, 158, 173, 176 Immune response, 8, 18, 20, 24, 27, 150, 153, 154, 162, 171, 173, 174, 179, 197, 201 Immune system, 4, 7, 8, 9, 13, 14, 15, 20, 153, 155, 156, 165, 173, 174, 178, 181, 201, 202 Immunity, 9, 14, 22, 60, 151, 163, 173, 175, 184 Immunization, 151, 173, 174 Immunologic, 14, 18, 19, 27, 151, 173 Immunologic Memory, 19, 173 Immunology, 11, 21, 27, 33, 48, 56, 150, 173 Immunomodulator, 19, 47, 173 Immunosuppressive, 170, 174, 198 Immunosuppressive therapy, 174 Immunotherapy, 13, 151, 156, 174 Impairment, 155, 167, 174, 179 Implantation, 161, 174
208
Crohn Disease
In situ, 12, 21, 27, 174 In Situ Hybridization, 12, 21, 27, 174 In vitro, 17, 18, 19, 22, 25, 49, 169, 174, 195, 198 In vivo, 25, 34, 169, 174, 178, 198 Incidental, 62, 174 Incision, 160, 174, 176 Induction, 18, 25, 152, 174 Infancy, 134, 174 Inflammatory bowel disease, 4, 7, 10, 11, 12, 14, 19, 20, 21, 24, 26, 48, 49, 74, 76, 87, 88, 174 Informed Consent, 125, 128, 133, 174 Ingestion, 21, 174, 188 Initiation, 16, 23, 175, 199 Initiator, 175 Inorganic, 74, 175, 181, 188 Insight, 14, 18, 22, 175 Insulin, 77, 175 Insulin-dependent diabetes mellitus, 175 Insulin-like, 77, 175 Interferon, 17, 175 Interferon-alpha, 175 Interleukin-1, 18, 30, 32, 47, 50, 175 Interleukin-10, 18, 30, 50, 175 Interleukin-12, 32, 47, 175 Interleukin-2, 19, 67, 175 Interleukins, 175, 178 Intervention Studies, 27, 175 Intestinal Flora, 18, 75, 176 Intestinal Mucosa, 17, 166, 176 Intestine, 3, 4, 7, 8, 16, 19, 24, 50, 157, 166, 176, 177 Intracellular, 22, 174, 176, 183, 190, 195 Intravenous, 37, 51, 168, 176 Intrinsic, 155, 176 Intussusception, 69, 176 Invasive, 20, 32, 77, 173, 176, 178 Ions, 155, 165, 173, 176 Iris, 162, 167, 176, 191 Isoflavones, 74, 176 J Jejunoileal Bypass, 155, 176 Jejunostomy, 166, 176 Jejunum, 88, 155, 176 K Karyotype, 101, 176 Kb, 11, 176 Keratitis, 37, 176 Kidney Disease, 5, 136, 173, 176 Kidney Failure, 110, 176, 177 Kidney Failure, Acute, 176
Kidney Failure, Chronic, 176, 177 Kidney stone, 173, 177 Kinetic, 23, 177 L Laceration, 177, 198 Lag, 19, 177 Laminin, 155, 177 Large Intestine, 3, 158, 164, 176, 177, 192, 196 Lesion, 177, 178, 200 Leucine, 9, 177 Leucocyte, 151, 166, 177 Leukaemia, 53, 177 Leukapheresis, 154, 177 Leukemia, 51, 52, 79, 159, 169, 177 Ligands, 15, 177 Linkage, 11, 15, 22, 25, 47, 51, 52, 170, 177 Linkage Disequilibrium, 11, 22, 25, 177 Lipid, 42, 53, 175, 177, 181 Lipopolysaccharides, 22, 177 Liver, 38, 59, 105, 150, 151, 155, 159, 164, 167, 168, 169, 171, 172, 177, 178, 189, 194 Liver Cirrhosis, 38, 177 Liver scan, 178, 194 Localization, 26, 45, 178 Localized, 150, 174, 177, 178, 187, 194, 198, 200 Lumbar, 178, 191 Lupus, 178, 198 Lymph, 62, 166, 172, 178, 194 Lymph node, 178, 194 Lymphatic, 166, 174, 178, 196 Lymphatic system, 178, 196 Lymphocyte Transformation, 21, 178 Lymphocytes, 48, 153, 164, 173, 175, 177, 178, 182, 187, 196, 198, 202 Lymphocytic, 159, 178 Lymphoid, 75, 78, 153, 177, 178 Lymphoma, 40, 47, 79, 178 Lysine, 172, 178 Lytic, 178, 195 M Macrophage, 16, 25, 107, 175, 178 Magnetic Resonance Imaging, 43, 55, 178, 194 Maintenance therapy, 72, 178 Major Histocompatibility Complex, 171, 178 Malabsorption, 13, 81, 179 Malignant, 150, 153, 179, 182 Malnutrition, 151, 157, 179 Mammography, 115, 179
Index 209
Mannans, 168, 179 Measles Virus, 25, 43, 179 Mediator, 78, 175, 179 Medical Records, 115, 128, 179 MEDLINE, 137, 179 Meiosis, 106, 179, 198 Melanoma, 179, 200 Memory, 153, 164, 179 Meninges, 158, 179 Mental, iv, 10, 120, 122, 124, 136, 138, 159, 161, 163, 165, 179, 191, 194, 200, 201 Mental Retardation, 120, 122, 124, 179 Mentors, 27, 179 Mercaptopurine, 20, 33, 64, 179 Mesenteric, 31, 54, 62, 75, 179 Mesentery, 44, 179, 186 Meta-Analysis, 33, 63, 180 Metabolite, 20, 180 Metastasis, 180, 182 Metastatic, 54, 64, 66, 69, 180 Methyltransferase, 20, 33, 64, 180 Microbe, 180, 199 Microbiology, 11, 20, 21, 77, 154, 180 Microcirculation, 177, 180 Micronutrients, 53, 180 Microorganism, 88, 160, 180, 185, 201 Micro-organism, 170, 180, 187 Microscopy, 155, 180 Milliliter, 156, 180 Mineralocorticoids, 151, 162, 180 Miscarriage, 127, 180 Misoprostol, 40, 180 Mitochondria, 97, 98, 110, 116, 117, 180, 184 Mitochondrial Swelling, 180, 182 Mitosis, 106, 154, 180 Modification, 181, 192 Monitor, 181, 183 Monoclonal, 16, 49, 94, 181, 192 Monocyte, 17, 181 Mononuclear, 73, 75, 78, 87, 181, 200 Monosomy, 110, 152, 181 Morbillivirus, 179, 181 Morphological, 166, 168, 181 Mosaicism, 107, 181 Motility, 45, 181 Mucosa, 16, 17, 24, 88, 178, 181 Mucus, 181, 200 Multidrug resistance, 60, 181 Multiple sclerosis, 181, 184 Mutagenesis, 22, 25, 181 Mutagens, 168, 181
Myelodysplastic Syndromes, 68, 181 Myelotoxic, 20, 181 Myotonic Dystrophy, 119, 182, 200 N Naloxone, 182 Naltrexone, 13, 182 Narcotic, 182 Nasogastric, 67, 166, 182 Natural killer cells, 175, 182 Nausea, 165, 169, 182, 200, 201 NCI, 1, 135, 159, 182, 186 Necrosis, 70, 154, 182, 194 Neoplasms, 151, 153, 171, 182 Nephropathy, 48, 176, 182 Nervous System, 119, 151, 158, 179, 197 Neural, 151, 172, 182 Neuritis, 182, 184 Neuropathy, 10, 116, 182, 186 Neurotransmitter, 150, 157, 170, 182, 197 Neutropenia, 168, 182 Neutrophils, 21, 151, 171, 182, 183 Nitric Oxide, 62, 183 Nitrogen, 152, 170, 177, 183 Nonverbal Communication, 183, 191 Nuclear, 8, 10, 62, 67, 97, 166, 167, 169, 182, 183 Nuclear Envelope, 97, 183 Nuclear Pore, 183 Nuclei, 165, 169, 172, 178, 180, 183, 191 Nucleic acid, 155, 163, 172, 174, 181, 191, 192, 193 Nucleic Acid Hybridization, 172, 183 Nurse Practitioners, 125, 183 Nutritional Status, 73, 183 Nutritional Support, 74, 169, 183 O Ointments, 165, 183 Oliguria, 176, 184 Omega-3 fatty acid, 78, 79, 184 Opiate, 166, 182, 184 Opioid Peptides, 184 Opsin, 184, 193 Optic disc, 184 Optic Nerve, 184, 193 Optic Neuritis, 63, 184 Orbital, 57, 58, 184 Organ Culture, 74, 184 Organelles, 96, 97, 163, 184, 188 Orofacial, 67, 184
182,
195,
168,
184, 183,
210
Crohn Disease
Osmotic, 151, 180, 184 Osteoblasts, 41, 184 Osteoporosis, 73, 151, 184 Ovaries, 124, 184, 195 Ovary, 185, 188 Oxaliplatin, 74, 185 Oxidation, 42, 150, 153, 163, 170, 185, 198 Oxidative Phosphorylation, 98, 185 Oxytocic, 180, 185 P Paediatric, 60, 62, 185 Palliative, 185, 198 Pancreas, 150, 164, 169, 171, 175, 185 Pancreatic, 51, 81, 185 Pancreatitis, 47, 185 Pancytopenia, 64, 185 Paratuberculosis, 20, 27, 185 Parotid, 185, 194 Partial remission, 185, 193 Particle, 185, 199 Paternity, 124, 185 Pathogen, 12, 185 Pathologic, 28, 54, 154, 156, 162, 173, 185, 191 Pathologic Processes, 154, 185 Pathophysiology, 11, 76, 90, 185 Patient Education, 30, 149, 185 PDQ, 135, 186 Pelvis, 150, 177, 178, 184, 186, 201 Pepsin, 180, 186 Peptide, 22, 24, 28, 61, 169, 184, 186, 188, 190 Peptide T, 28, 186 Percutaneous, 30, 58, 59, 186 Perforation, 37, 65, 186 Perianal, 39, 40, 48, 59, 67, 186 Pericardium, 186, 198 Perineal, 41, 46, 186 Perineum, 186 Peripheral blood, 12, 21, 78, 171, 175, 186 Peripheral Neuropathy, 67, 186 Peripheral stem cells, 171, 186 Peritoneum, 179, 186 Peroral, 33, 186 PH, 35, 44, 156, 186 Phagocytosis, 20, 186 Pharmaceutical Solutions, 165, 186 Pharmacologic, 187, 199 Phenotype, 14, 19, 60, 187 Phospholipases, 187, 196 Phospholipids, 167, 187 Phosphorus, 157, 187
Phosphorylation, 98, 187 Physical Examination, 122, 187 Physiologic, 180, 187, 190, 192, 195 Physiology, 169, 187 Phytohemagglutinins, 178, 187 Pigments, 157, 187, 188, 193 Pilot study, 12, 13, 16, 32, 56, 79, 187 Pituitary Gland, 28, 162, 187, 190, 195 Plant Diseases, 166, 187 Plants, 163, 170, 187, 188, 194, 199 Plasma, 29, 42, 53, 75, 97, 151, 153, 171, 176, 177, 180, 187, 188 Plasma cells, 153, 187 Plasma protein, 151, 187 Plasmapheresis, 154, 188 Plastids, 184, 188 Platelet Activation, 188, 196 Platelet Aggregation, 183, 188 Plateletpheresis, 154, 188 Platelets, 183, 185, 188 Platinum Compounds, 185, 188 Pneumonia, 162, 188 Pneumonitis, 47, 188 Poisoning, 169, 182, 188 Pollen, 20, 188 Polymorphic, 20, 25, 188 Polymorphism, 11, 15, 29, 59, 73, 126, 188 Polypeptide, 22, 152, 160, 173, 188, 202 Polysaccharide, 153, 188, 190 Polyunsaturated fat, 75, 188 Posterior, 152, 176, 184, 185, 188 Postmenopausal, 151, 184, 188 Postoperative, 60, 76, 78, 168, 188 Postsynaptic, 189, 196 Potentiates, 175, 189 Potentiating, 16, 189 Potentiation, 16, 189, 196 Practicability, 167, 189 Practice Guidelines, 138, 189 Precipitating Factors, 158, 189 Preclinical, 13, 27, 189 Precursor, 165, 166, 169, 189, 190 Prednisolone, 189 Prednisone, 18, 29, 66, 189 Prenatal, 124, 127, 166, 189 Prevalence, 21, 26, 60, 112, 189 Primary endpoint, 20, 189 Probe, 15, 189 Progesterone, 189, 197 Progression, 27, 189 Progressive, 111, 158, 159, 164, 165, 167, 177, 182, 188, 190
Index 211
Promoter, 24, 190 Prone, 39, 110, 119, 190 Pro-Opiomelanocortin, 169, 184, 190 Prophylaxis, 76, 190 Prospective study, 23, 30, 62, 190 Prostaglandin, 180, 190 Protein Folding, 23, 190 Proteoglycans, 155, 190 Proteolytic, 151, 161, 190 Protocol, 130, 191 Protons, 173, 191, 192 Protozoa, 180, 191 Psoas Abscess, 34, 58, 191 Psoriasis, 49, 191 Psychic, 179, 191 Psychotherapy, 74, 191 Public Policy, 137, 191 Pulmonary, 156, 157, 166, 176, 191, 201 Pulmonary Artery, 156, 191, 201 Pulmonary Edema, 176, 191 Pulse, 23, 181, 191 Pupil, 162, 184, 191 Purines, 155, 191 Purulent, 191 Putrefaction, 169, 191 Pyoderma, 44, 49, 50, 56, 61, 63, 191 Pyoderma Gangrenosum, 44, 50, 56, 63, 191 Pyrimidines, 155, 192 Q Quality of Life, 13, 20, 192, 198 Quaternary, 190, 192 Quiescent, 50, 192 R Race, 176, 192 Radiation, 150, 168, 192, 194, 200, 202 Radiation therapy, 150, 192 Radioactive, 157, 173, 174, 178, 183, 192, 194 Radiography, 60, 192 Radiological, 45, 53, 55, 186, 192 Randomized, 13, 28, 51, 66, 72, 73, 79, 165, 192 Receptor, 10, 16, 62, 73, 113, 153, 170, 186, 192, 195 Recombinant, 69, 130, 192, 201 Recombination, 169, 170, 192 Rectal, 31, 62, 64, 81, 192 Rectum, 88, 153, 154, 157, 160, 164, 168, 169, 174, 177, 192 Recur, 4, 192 Recurrence, 56, 60, 65, 76, 192
Red blood cells, 4, 167, 172, 192, 194 Refer, 1, 102, 106, 108, 113, 132, 157, 160, 178, 192, 199 Refraction, 192, 196 Refractory, 20, 41, 47, 50, 60, 67, 193 Regimen, 165, 193 Regional enteritis, 88, 146, 193 Relapse, 12, 19, 53, 77, 193 Remission, 12, 18, 27, 53, 65, 77, 79, 89, 178, 192, 193 Reproductive cells, 110, 120, 121, 170, 172, 193 Resection, 31, 45, 52, 56, 66, 193 Response rate, 91, 193 Restitution, 32, 193 Retina, 161, 184, 193, 194 Retinal, 56, 184, 193 Retinoblastoma, 112, 193 Retinol, 193 Retrobulbar, 63, 184, 193 Retroviral vector, 169, 193 Rheumatoid, 15, 65, 193 Rheumatoid arthritis, 65, 193 Rhodopsin, 184, 193 Ribonucleic acid, 104, 193 Ribose, 150, 194 Ribosome, 23, 104, 194, 199 Risk factor, 4, 5, 13, 25, 27, 45, 48, 54, 158, 190, 194 Rods, 168, 193, 194 Ruminants, 27, 194 S Sacroiliac Joint, 36, 194 Saimiri, 48, 194 Salivary, 164, 194 Salivary glands, 164, 194 Saponins, 194, 197 Sarcoidosis, 10, 21, 31, 142, 194 Scans, 14, 15, 194 Scatter, 194, 200 Schizophrenia, 117, 194 Scleroderma, 15, 194 Sclerosis, 113, 181, 194 Screening, 25, 64, 91, 115, 124, 125, 127, 160, 186, 194 Secretion, 28, 30, 162, 172, 175, 180, 181, 195, 201 Segregation, 68, 192, 195 Selenium, 53, 195 Sella, 187, 195 Sella Turcica, 187, 195 Senna, 84, 195
212
Crohn Disease
Sepsis, 168, 195 Septic, 58, 154, 195 Sequence Homology, 186, 195 Sequencing, 132, 195 Serologic, 28, 195 Serology, 28, 71, 195 Serum, 14, 21, 41, 77, 151, 160, 177, 180, 195, 200 Sex Characteristics, 151, 152, 195 Shivering, 195, 198 Shock, 21, 59, 195, 200 Side effect, 13, 92, 131, 134, 151, 156, 195, 198, 199 Sigmoid, 195 Sigmoidoscopy, 88, 148, 195 Signal Transduction, 17, 195 Signs and Symptoms, 4, 118, 119, 124, 193, 196, 200 Small intestine, 3, 8, 17, 24, 35, 38, 51, 88, 155, 158, 165, 166, 172, 173, 176, 182, 193, 196 Social Environment, 192, 196 Social Work, 121, 196 Soft tissue, 156, 196 Soma, 196 Somatic, 74, 107, 110, 121, 151, 172, 179, 180, 186, 196 Somatic cells, 107, 110, 121, 179, 180, 196 Somatic mutations, 110, 196 Soybean Oil, 188, 196 Specialist, 125, 144, 196 Species, 12, 18, 23, 134, 151, 158, 169, 172, 176, 179, 181, 192, 194, 195, 196, 197, 200, 201 Specificity, 87, 196 Spectrum, 14, 43, 196 Sperm, 106, 107, 110, 119, 120, 121, 124, 131, 152, 159, 170, 172, 188, 193, 196 Spinal cord, 158, 159, 179, 182, 196 Spleen, 178, 194, 196 Sporadic, 193, 197 Staging, 194, 197 Standardize, 25, 197 Stem Cells, 167, 171, 186, 197 Stenosis, 63, 197 Steroid, 19, 62, 66, 74, 162, 194, 197 Stillbirth, 122, 197 Stimulus, 13, 165, 173, 177, 197 Stoma, 30, 197 Stomach, 81, 150, 153, 154, 155, 164, 166, 167, 169, 172, 182, 186, 194, 196, 197 Stool, 26, 148, 160, 177, 197
Strand, 34, 97, 197 Stress, 162, 169, 182, 193, 197 Stricture, 197 Stroke, 115, 136, 157, 197 Stroma, 17, 176, 197 Stromal, 16, 18, 197 Subacute, 174, 197 Subclinical, 174, 197 Subcutaneous, 165, 197 Subspecies, 196, 197 Supplementation, 77, 79, 198 Supportive care, 186, 198 Suppression, 47, 162, 198 Symptomatic, 36, 44, 67, 142, 185, 198 Synaptic, 182, 196, 198 Systemic, 37, 67, 93, 156, 174, 189, 192, 194, 198 Systemic lupus erythematosus, 37, 198 T Tacrolimus, 67, 198 Terminator, 160, 198 Tetani, 198 Tetanic, 198 Tetanus, 49, 198 Thalidomide, 41, 67, 68, 94, 198 Therapeutics, 14, 78, 79, 93, 198 Thermogenesis, 42, 198 Thigh, 171, 198 Thioguanine, 20, 198 Threonine, 186, 198 Thrombin, 188, 190, 199 Thrombomodulin, 190, 199 Thrombosis, 37, 51, 190, 197, 199 Thyroid, 124, 199 Thyroid Gland, 124, 199 Thyroid Hormones, 199 Thyroxine, 151, 199 Tolerance, 20, 30, 150, 199 Tomography, 34, 36, 44, 65, 69, 199 Topical, 67, 199 Toxic, iv, 69, 96, 172, 173, 182, 195, 199 Toxicity, 20, 130, 165, 199 Toxicology, 137, 199 Toxin, 166, 198, 199 Trachea, 199 Transcription Factors, 105, 199 Transduction, 18, 195, 199 Transfection, 25, 156, 169, 199 Translation, 104, 105, 169, 199 Translational, 19, 200 Transmitter, 150, 179, 200 Transplantation, 9, 173, 177, 179, 200
Index 213
Trauma, 167, 182, 185, 200 Trinucleotide Repeat Expansion, 119, 200 Trinucleotide Repeats, 200 Trisomy, 69, 110, 153, 200 Tuberculosis, 21, 54, 178, 200 Tumor Necrosis Factor, 13, 23, 30, 49, 76, 198, 200 Tunica, 181, 200 U Ulcer, 54, 88, 180, 200 Ulcerative colitis, 4, 12, 16, 21, 30, 37, 43, 48, 49, 59, 60, 61, 62, 64, 70, 73, 74, 78, 79, 87, 88, 90, 91, 143, 174, 191, 200 Ultrasonography, 31, 69, 200 Ultraviolet radiation, 107, 200 Uraemia, 185, 200 Uremia, 176, 201 Urine, 154, 156, 173, 176, 177, 184, 201 Uterus, 124, 184, 185, 189, 201 V Vaccine, 150, 191, 201 Vacuoles, 184, 201 Vagina, 4, 148, 201, 202 Vaginal, 201 Vascular, 62, 65, 67, 166, 174, 177, 180, 183, 199, 201 Vasculitis, 56, 185, 201 Vasodilators, 183, 201
Vector, 129, 130, 199, 201 Vein, 62, 176, 183, 185, 201 Venous, 190, 201 Ventricle, 173, 191, 201 Venules, 62, 156, 157, 180, 201 Vertebrae, 191, 196, 201 Veterinary Medicine, 137, 201 Viral, 70, 129, 169, 170, 199, 201 Virulence, 199, 201 Virus, 71, 78, 129, 170, 175, 193, 199, 201 Viscera, 179, 196, 201 Vitro, 19, 124, 201 Vivo, 25, 201 Vulva, 54, 201 W White blood cell, 107, 153, 156, 159, 178, 181, 182, 183, 187, 202 Windpipe, 199, 202 Womb, 201, 202 Wound Healing, 13, 202 X X-ray, 19, 156, 161, 168, 183, 192, 194, 202 Y Yeasts, 168, 176, 187, 202 Z Zygote, 161, 181, 202 Zymogen, 190, 202
