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

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

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PANCREATITIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Pancreatitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84149-7 1. Pancreatitis-Popular works. I. Title.

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

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

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

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

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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON PANCREATITIS........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Pancreatitis ................................................................................. 26 E-Journals: PubMed Central ....................................................................................................... 79 The National Library of Medicine: PubMed ................................................................................ 80 CHAPTER 2. NUTRITION AND PANCREATITIS ............................................................................... 125 Overview.................................................................................................................................... 125 Finding Nutrition Studies on Pancreatitis ................................................................................ 125 Federal Resources on Nutrition ................................................................................................. 133 Additional Web Resources ......................................................................................................... 134 CHAPTER 3. ALTERNATIVE MEDICINE AND PANCREATITIS ........................................................ 135 Overview.................................................................................................................................... 135 National Center for Complementary and Alternative Medicine................................................ 135 Additional Web Resources ......................................................................................................... 148 General References ..................................................................................................................... 149 CHAPTER 4. DISSERTATIONS ON PANCREATITIS .......................................................................... 151 Overview.................................................................................................................................... 151 Dissertations on Pancreatitis..................................................................................................... 151 Keeping Current ........................................................................................................................ 152 CHAPTER 5. CLINICAL TRIALS AND PANCREATITIS ..................................................................... 153 Overview.................................................................................................................................... 153 Recent Trials on Pancreatitis ..................................................................................................... 153 Keeping Current on Clinical Trials ........................................................................................... 155 CHAPTER 6. PATENTS ON PANCREATITIS ..................................................................................... 157 Overview.................................................................................................................................... 157 Patents on Pancreatitis .............................................................................................................. 157 Patent Applications on Pancreatitis .......................................................................................... 175 Keeping Current ........................................................................................................................ 196 CHAPTER 7. BOOKS ON PANCREATITIS ......................................................................................... 197 Overview.................................................................................................................................... 197 Book Summaries: Federal Agencies............................................................................................ 197 Book Summaries: Online Booksellers......................................................................................... 204 The National Library of Medicine Book Index ........................................................................... 206 Chapters on Pancreatitis ............................................................................................................ 207 CHAPTER 8. MULTIMEDIA ON PANCREATITIS .............................................................................. 211 Overview.................................................................................................................................... 211 Video Recordings ....................................................................................................................... 211 Audio Recordings....................................................................................................................... 213 Bibliography: Multimedia on Pancreatitis................................................................................. 213 CHAPTER 9. PERIODICALS AND NEWS ON PANCREATITIS ........................................................... 217 Overview.................................................................................................................................... 217 News Services and Press Releases.............................................................................................. 217 Newsletter Articles .................................................................................................................... 221 Academic Periodicals covering Pancreatitis .............................................................................. 223 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 225 Overview.................................................................................................................................... 225 U.S. Pharmacopeia..................................................................................................................... 225 Commercial Databases ............................................................................................................... 227 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 231

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Overview.................................................................................................................................... 231 NIH Guidelines.......................................................................................................................... 231 NIH Databases........................................................................................................................... 233 Other Commercial Databases..................................................................................................... 235 The Genome Project and Pancreatitis ........................................................................................ 235 APPENDIX B. PATIENT RESOURCES ............................................................................................... 241 Overview.................................................................................................................................... 241 Patient Guideline Sources.......................................................................................................... 241 Finding Associations.................................................................................................................. 245 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 249 Overview.................................................................................................................................... 249 Preparation................................................................................................................................. 249 Finding a Local Medical Library................................................................................................ 249 Medical Libraries in the U.S. and Canada ................................................................................. 249 ONLINE GLOSSARIES................................................................................................................ 255 Online Dictionary Directories ................................................................................................... 257 PANCREATITIS DICTIONARY ................................................................................................ 259 INDEX .............................................................................................................................................. 361

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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 pancreatitis 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 pancreatitis, 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 pancreatitis, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on pancreatitis. 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 pancreatitis, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on pancreatitis. The Editors

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

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and pancreatitis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “pancreatitis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Understanding Pancreatitis and Pancreatic Cancer Source: Digestive Health and Nutrition. 3(3): 17-20. May-June 2001. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email: [email protected]. Summary: Acute pancreatitis (inflammation of the pancreas) can happen to anyone, anytime. However, repeated episodes put the patient at risk for chronic pancreatitis and pancreatic cancer, so it is important to learn about the risk factors and symptoms of these diseases. This article reviews the presenting symptoms of pancreatitis, the anatomy and physiology of the healthy pancreas, treatment options, and the risk factors for pancreatic cancer. The most common cause of acute pancreatitis is gallstones that get

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caught at the opening into the small intestine. Excessive alcohol use is another common cause of the disease. Diagnosis can include blood tests, an abdominal CT (computed tomography) scan, and endoscopic ultrasound. Treatment for acute pancreatitis is usually relatively low tech, featuring hydration (adequate fluids), pain management, and nutrition support (intravenous). During an episode of acute pancreatitis, which can last days or even a week, patients usually do not eat any food at all initially. Clear liquids and then low fat foods are added gradually as symptoms improve. When gallstones cause pancreatitis, surgery to remove them is usually necessary. For those who already have chronic pancreatitis or are at risk for developing it, a healthy lifestyle and positive attitude are essential. Many people with pancreatitis find that a low fat diet helps reduce the severity of acute episodes and also slows the progression of the chronic disease. One sidebar offers a description of hereditary pancreatitis, which is a rare condition. The final section of the article discusses pancreatic cancer, noting that both chronic and hereditary pancreatitis put people at higher risk for developing pancreatic cancer. Appended to the article is a list of websites for readers who want to locate additional information about pancreatitis. 2 figures. •

Identification of Pancreatitis in the Ambulatory Setting Source: Gastroenterology Nursing. 24(1): 20-22. January-February 2001. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: Acute pancreatitis can be life threatening and nurse practitioners must know the signs, symptoms, and risk factors for pancreatitis. This article reviews the identification of pancreatitis in the ambulatory setting. The author uses a case study of a 59 year old white woman who presents to the clinic with vague complaints of abdominal pain. Her symptoms began the evening before presentation and are progressively worsening. The author uses this case to illustrate the differential diagnostic process. The most common differential diagnoses for this patient's symptoms include appendicitis, acute pancreatitis, mesenteric ischemia or infarction, perforated gastric or duodenal ulcer, intestinal obstruction, biliary colic, and perhaps even inferior wall myocardial infarction. Making a diagnosis of acute pancreatitis depends on clinical history, physical examination, serum enzyme assays, and radiologic tests. The main goal of treatment for pancreatitis is supportive care, limitation of complications, and prevention of necrosis (tissue death) of the pancreas. In the case example, the patient's pancreatitis was thought to be caused by a mixture of estrogen and an ACE inhibitor. Although alcohol consumption and gallstones are the most frequent causes of pancreatitis in the general population, mediations are now being recognized as important causative agents that are often overlooked. The author reiterates that early recognition and treatment of acute pancreatitis can reduce suffering and serious complications for the patient. 3 tables. 7 references.

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Fungal Infection in Acute Necrotizing Pancreatitis Source: Journal of the American College of Surgeons. 188(4): 408-414. April 1999. Summary: Anecdotal reports suggest that patients with fungal infection of necrotizing pancreatitis (NP) have worse outcomes than those with bacterial infections. This article reports on a study undertaken to compare the clinical course and outcomes of patients with NP infected with fungal versus nonfungal organisms. Data collected prospectively from 1983 through 1995 on 57 patients with infected NP (1983 through 1995) were reviewed. Seven patients (12 percent) developed fungal infection, and 50 (88 percent)

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developed bacterial infection. Groups had similar mean ages (60 versus 63 years) and APACHE II scores on admission. The cause of NP was ERCP (endoscopic retrograde cholangiopancreatography) induced in 3 of 7 with fungal infection versus 3 of 50 with bacterial infection. Patients with fungal infection had been treated with a mean of 4 different antibiotics for a mean of 23 days, and 4 of 7 (57 percent) required preoperative mechanical ventilation. In addition, postoperative intensive care unit stays were longer (20 versus 10 days), as were total hospital stays (59 versus 41 days). Mortality was higher with fungal infections; 3 of 7 patients (43 percent) died, versus 10 of 50 patients with bacterial infection (20 percent). The authors conclude that although NP presents with similar initial severity, patients with fungal infection tend to have a more complicated course and worse outcomes than those with bacterial infection. They recommend that low dose antifungal prophylaxis should be added to the early management of NP. 1 figure. 1 table. 33 references. (AA-M). •

Biliary Tract Disease and Pancreatitis in Pregnancy Source: Practical Gastroenterology. 15(2): 46-48, 51. February 1991. Summary: Biliary colic, acute cholecystitis, and acute pancreatitis occasionally complicate pregnancy and can result in difficult diagnostic and therapeutic challenges. Pregnancy seems to predispose women to gallstone formation. However, since cholelithiasis is common in women of childbearing age, the biliary tract disease that sometimes occurs in pregnant women may be coincidental rather than the result of pregnancy. Initial treatment of both biliary tract disease and pancreatitis in pregnancy is almost always medical, especially in the first and third trimesters. Elective surgery, when indicated, may be safely carried out during the second trimester or after delivery. In the vast majority of cases, acute biliary and pancreatic disorders, if properly managed, do not adversely affect the pregnancy. 18 references. (AA-M).

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Regression of Liver Fibrosis After Biliary Drainage in Patients with Chronic Pancreatitis and Stenosis of the Common Bile Duct Source: New England Journal of Medicine. 344(6): 418-423. February 8, 2001. Summary: Chronic obstruction of the common bile duct may cause hepatic (liver) fibrosis and secondary biliary cirrhosis (scarring). This article reports on a study of liver biopsy specimens from 11 patients with chronic stenosis (narrowing) of the common bile duct due to chronic pancreatitis (inflammation of the pancreas). All the patients had undergone liver biopsy before or at the time of surgical biliary decompression and all underwent a subsequent liver biopsy for various clinical reasons. The patients were followed as part of a prospective study of 501 patients who had been treated for chronic pancreatitis. Two pathologists, who were unaware of the sequence of specimens, graded fibrosis on a scale of 0 (none) to 3 (cirrhosis). The 11 patients were all men. Chronic pancreatitis was due to alcohol abuse in 10 of the men; 1 had idiopathic disease. The median age at diagnosis was 38 years. The median interval between the first and second liver biopsies was 2.5 years (range of 0.3 to 9.0 years). The two patients who had restenosis of the biliary anastomosis were excluded from the analysis. In the remaining group of nine patients, the second specimen showed significant improvement in fibrosis. The fibrosis improved by two grades in two patients and by one grade in four patients; in three patients, the grade did not change. The pathologists agreed on the grading of specimens from 10 of the 11 patients. The authors conclude that, in patients with chronic pancreatitis and stenosis of the common bile duct, liver fibrosis may regress after biliary drainage. 1 figure. 2 tables. 24 references.

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Chronic Pancreatitis: Complications and Management Source: Journal of Clinical Gastroenterology. 29(3): 225-240. October 1999. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. In the majority of cases, particularly in Western populations, the disease is associated with alcohol abuse. This article reviews recent research and prevailing concepts regarding the three major complications of chronic pancreatitis: abdominal pain, malabsorption, and diabetes. Of these, pain is the most difficult to treat and is therefore the most frustrating symptom for both the patient and the physician. While analgesics form the cornerstone of pain therapy, a number of other treatment modalities (inhibition of pancreatic secretion, antioxidants, and surgery) have also been described. Unfortunately, the efficacy of these treatments is hard to assess, primarily because of the lack of properly controlled clinical trials. Replacement of pancreatic enzymes (particularly lipase) in the gut is the mainstay of treatment for malabsorption. Diabetes secondary to chronic pancreatitis is difficult to control and its course is often complicated by hypoglycemic attacks. Therefore, it is essential that caution is exercised when treating this condition with insulin. The authors also present a discussion of current opinion on clinical issues relating to the other known complications of chronic pancreatitis, including pseudocysts, venous thromboses, biliary and duodenal obstruction, biliary cirrhosis, and pancreatic cancer. 2 figures. 2 tables. 170 references.

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Serial Computed Tomography Is Rarely Necessary in Patients with Acute Pancreatitis: A Prospective Study in 102 Patients Source: Journal of the American College of Surgeons. 193(2): 146-152. August 2001. Contact: Available from Journal of the American College of Surgeons. P.O. Box 2127, Marion, OH 43306-8227. (800) 214-8489 or (740) 382-3322. Fax (740) 382-5866. Summary: Computed tomography (CT) has proved to be helpful in patients with acute pancreatitis for differentiating between mild and severe forms. Follow up of acute pancreatitis with CT has been advocated but rarely studied. This article reports on a study undertaken to determine if late CT performed at day 7 might be helpful in establishing the prognosis or the type of complications, and to select a subgroup of patients with pancreatitis in whom CT could be beneficial. Contrast enhanced CT was performed at the admission day and 7 days after admission in 102 patients admitted for acute pancreatitis. The extent of pancreatic inflammation was classified according to Balthazar grade, and intrapancreatic necrosis (tissue death) on these examinations was prospectively assessed and compared with clinical and biologic data and with patient outcomes. Among 102 patients, complications developed in 24 (23 percent). Complications developed in only 8 percent of patients with Ranson score less than 2, making routine early CT unnecessary. For the patients with Ranson score less than 2 and Balthazar grades A and B at day 1 CT, late CT seemed to be useless. Complication was suspected by clinical and biologic tests before day 7 in 22 of 24 complicated patients (94 percent), suggesting that CT could be proposed only in cases of clinical or biologic deterioration. Late CT was correlated with a complicated course in patients with Balthazar grades D and E or intrapancreatic necrosis greater than 50 percent. Late CT was predictive of complications in cases of intrapancreatic necrosis enlarging since the first examination. The authors conclude that in cases of acute pancreatitis, there is little justification for systematic early CT, especially in patients with Ranson score less than 2,

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and late CT does not need to be performed routinely, but only in cases of clinical or biologic worsening. 2 figures. 4 tables. 26 references. •

Better Test for Pancreatitis? Source: Emergency Medicine. 22(16): 109. September 30, 1990. Summary: Elevated serum amylase and the clinical picture usually identify acute pancreatitis within 24 hours after the onset of an attack. This brief article discusses the use of a serum lipase test followed, if necessary, by computed tomography (CAT Scan), to reliably confirm the diagnosis. CAT scanning can reveal the presence and extent of pancreatic necrosis and, therefore, the risk of local or systemic complications. The author concludes that initial management of patients thought to have acute pancreatitis, even before the results of the blood tests are available, should include immediate hydration with intravenously-delivered fluids, decompression of the stomach, and the cessation of any oral intake.

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Non-Surgical Treatment for Gallstone Pancreatitis Source: Current Topics in Gastroenterology. March 1992. p. 4. Summary: Gallstone pancreatitis is a painful and potentially serious condition caused by gallstones passing from the gallbladder and causing inflammation of the pancreas. This article reports on the use of a non-surgical treatment for gallstone pancreatitis: endoscopic retrograde cholangiopancreatography (ERCP), with sphincterotomy. The article discusses patient selection, indications for the procedure, the techniques used, and the results obtained in a group of 15 patients who were treated with this technique. The researchers conclude that ERCP with sphincterotomy is a safe alternative to gallbladder surgery in high risk patients with gallstone pancreatitis.

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Experimental Pancreatitis Source: Current Opinion in Gastroenterology. 7(5): 702-708. October 1991. Summary: Given the practical limitations of clinical research in acute pancreatitis, experimental animal models represent the primary means for investigating the pathophysiology of pancreatitis and of initially testing potential therapeutic modalities. This review article describes recent studies of pathophysiology mechanisms that have evaluated a number of factors, including possible injurious effects of nicotine on the pancreas, alterations in normal exocrine secretory processes, the role of oxygen-derived free radicals, effects of acute pancreatitis on other organs and physiologic functions, and the contribution of stress to the severity of pancreatitis. Investigations of potential therapies have included cholecystokinin-receptor antagonists, peritoneal lavage with protease inhibitors, prostaglandin analogues, and drugs that alter pancreatic blood flow and microvascular permeability. In addition, experimental models of pancreatitis are providing insights into mechanisms of pancreatic growth, differentiation, and repair. 35 annotated references. (AA).

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Refractory Pancreatitis Secondary to Ruptured Hepatocellular Carcinoma into the Common Bile Duct Source: Digestive Diseases and Sciences. 46(5): 1029-1033. May 2001. Contact: Available from Kluwer Academic Publishers. Customer Service Department, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Distribution Centre, P.O. Box

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322, 3300 AH Dordrecht, The Netherlands. 31 78 6392392. Fax: 31 78 6546474. E-mail: [email protected]. Summary: Hepatocellular carcinoma (HCC, liver cancer) is a common disease worldwide and continues to be the leading cause of death of males in Taiwan (from where this article originates). Jaundice is present in 19 to 44 percent of cases of HCC at the time of diagnosis and is usually attributed to the preexisting liver cirrhosis (scarring) or extensive hepatic parenchymal (the liver body) destruction by tumor. Icteric hepatoma (a type of liver tumor) is characterized by intermittent obstructive jaundice with associated complications, such as cholangitis (inflammation of the bile ducts) and hemobilia. In this article, the authors report the first case of icteric hepatoma that initially presented as pancreatitis in addition to obstructive jaundice. The 59 year old man was admitted with a 2 week history of tea colored urine, intermittent tarry stool, vomiting, and postprandial epigastralgia (pain in the stomach after meals) with radiation to his back. He denied alcohol abuse and drugs consumption and he had never experienced pancreatitis. After 8 days of hospital treatment, the patient was released and able to eat a normal diet at an outpatient visit one month later. However, he was rehospitalized 8 weeks later with another episode of pain; surgical treatment was implemented. The patient died of multisystem organ failure on the 32nd postoperative day. For this case, the treatment was focused on two goals. First, the consequences of the biliary obstruction including the pancreatitis should be resolved by nonoperative methods, if available. Second, the origin of the migrating tumor should be eradicated either by transarterial chemoembolization or hepatic (liver) resection. The present case was not suitable for hepatic resection or hepatic artery ligation because of intrahepatic metastasis of both lobes and portal vein thrombosis (clotting) seen at exploration. Although palliation could be satisfactorily given, the prognosis continues to be dismal. 4 figures. 11 references. •

Managing Acute Pancreatitis: New ACG Recommendations Source: Journal of Critical Illness. 12(8): 508-510, 511. August 1997. Summary: In early 1997, the American College of Gastroenterology (ACG) issued guidelines for the diagnosis and treatment of acute pancreatitis. The guidelines included the clinical terminology for acute pancreatitis and its complications, the appropriate criteria for determining the severity of the disorder, and the indications for medical and surgical treatment. This article provides summaries of these guidelines and includes recommendations for practical patient care. Topics include diagnostic guidelines, symptoms, laboratory findings, severity criteria, supportive care, and additional interventions. The goals of medical therapy for acute pancreatitis are to provide supportive care and to prevent systemic complications, pancreatic necrosis, and pancreatic infection. In a patient with mild pancreatitis, supportive care and monitoring for complications often are all that is required. However, when severe pancreatitis is present, ICU admission is indicated for the management of systemic complications, and additional diagnostic tests are needed to rule out pancreatic necrosis. A detailed patient care algorithm is provided. 1 figure. 1 table. 1 reference. (AA-M).

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Acute Pancreatitis: Diagnosis and Management Source: American Family Physician. 52(2): 435-443. August 1995. Summary: In this article, the authors outline the steps in the diagnosis and management of acute pancreatitis, a clinical syndrome characterized by midepigastric pain, nausea, and vomiting. Topics include definitions; etiology; medications associated with acute

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pancreatitis; pathophysiology; clinical presentation; laboratory tests; diagnostic tests, including serum amylase level, lipase, abdominal radiographs, ultrasonography, and computed tomography; prognostic criteria for acute pancreatitis; treatment; and the role of surgery. The authors note that, once a diagnosis of pancreatitis is confirmed, supportive therapy with intravenous hydration and close observation is effective in the majority of patients. Lack of improvement may indicate the need to search for a local complication such as pseudocyst or abscess. They stress that evidence of the systemic complications of pancreatitis mandates intensive care monitoring. 4 figures. 4 tables. 41 references. (AA-M). •

Acute Pancreatitis in Peritoneal Dialysis and Haemodialysis: Risk, Clinical Course, Outcome, and Possible Aetiology Source: Gut. 46(3): 385-389. March 2000. Contact: Available from BMJ Publishing Group. P.O. Box 590A, Kennebunkport, ME 04046. (800) 236-6265. Summary: It has been suggested that the incidence of acute pancreatitis (pancreas infection) in patients with end stage renal disease (ESRD, kidney failure) is increased. This article reports on a study undertaken to assess the risk of acute pancreatitis in patients on long term peritoneal dialysis (PD) and long term hemodialysis (HD) compared with the general population, to evaluate its clinical course and outcome, and to identify possible etiological factors. All patients from a large general hospital in The Netherlands who were maintained on long term PD or HD (total dialysis time more than six weeks) from January 1989 to March 1998 were included. In 269 patients on HD (total of 614 person years), one patient developed an attack of acute pancreatitis. Patients on hemodialysis did not show an increased risk for acute pancreatitis compared with the general population. In 128 patients on PD (total of 241 person years), seven patients had nine attacks of acute pancreatitis. Patients on PD had a significantly and highly increased risk for acute pancreatitis. Mortality in this series of nine attacks was 11 percent. No single etiological risk factor could be identified. The authors conclude that the risk of acute pancreatitis in patients on long term PD is significantly and highly increased compared with the general population. 3 tables. 22 references.

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Nutrition Support in Pancreatitis Source: Nutrition in Clinical Practice (NCP). 10(2): 45-53. April 1995. Contact: Available from Nutrition in Clinical Practice (NCP). American Society for Parenteral and Enteral Nutrition. 8630 Fenton Street, Suite 412, Silver Spring, MD 209103805. (301) 587-6315. Summary: Nutrition support in patients with pancreatitis has created a challenge for clinicians. Because the pancreas is normally stimulated by the ingestion of food, particularly fat, patients are often denied oral nutrition. This review article summarizes the etiologies and methods for staging pancreatitis; the physiology of pancreatic exocrine secretion; and the response of the pancreas to different methods of nutrition support. The authors review the results of clinical trials, which examine both parenteral and enteral nutrition in animals and humans with this disease. They also discuss recommendations for nutrition management of patients with acute and chronic pancreatitis, and areas for future research. 2 tables. 81 references. (AA-M).

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Acute Pancreatitis: Systemic Complications and Prognostic Assessment Source: Practical Gastroenterology. 15(8): 22, 27-30, 32. Summary: Once a diagnosis of acute pancreatitis (AP) has been made, its severity may range from mild, with abdominal pain, nausea and vomiting, to severe, with multisystem involvement. This article reviews the systemic complications and prognostic assessment of acute pancreatitis. The authors note that the management of AP has paralleled the understanding of the effects of the pancreatic gland's capacity to release hormones, enzymes, and peptides and their clinical manifestations. Advances in critical care permit survival of patients with severe fulminating pancreatitis. Death is primarily due to multisystem failure early on, or sepsis later, as secondary infection sets in. The authors discuss system complications (cardiac, renal, respiratory, and metabolic), infrequent system complications, measuring the severity of AP, peritoneal lavage, computed tomography, and the value of prognostic assessment. 5 tables. 27 references. (AA-M).

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Pain and Chronic Pancreatitis Source: European Journal of Gastroenterology and Hepatology. 3(6): 425-433. June 1991. Summary: Pain is the principal symptom of chronic pancreatitis, and relief of pain the principal aim of treatment. The mechanism of pain production has been a matter of considerable speculation, but remains unclear. This review article collates the available evidence regarding the cause of pain in chronic pancreatitis in an attempt to explain the variable results of treatment. Topics include pancreatic ductal pressure, biliary tract obstruction, pseudocyst formation, perineural inflammation and infiltration, interruption of pain pathways, significance of calcification, and the interplay of abstinence from alcohol, pancreatic function, and pain. 73 references.

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Pancreatic Enzyme Therapy and Nutritional Status of Outpatients with Chronic Pancreatitis Source: Gastroenterology Nursing. 24(2): 84-87. March-April 2001. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: Patients with chronic pancreatitis are at risk for poor nutritional status. The two major clinical features of chronic pancreatitis are abdominal pain and maldigestion, both resulting in malnutrition. Abdominal pain often results in decreased oral intake, and decreased enzyme production results in maldigestion. Enzyme therapy often is included in treating chronic pancreatitis. There is limited data on the nutritional assessment of outpatients with chronic pancreatitis, and the efficacy of the use of enzyme therapy remains controversial. Serum albumin (levels of protein in the blood) level and measurement of ideal body weight are two simple measures of nutritional status that can be obtained by gastroenterology nurses. This article reports on a retrospective chart review that was done on patients seen in the authors' outpatient clinic for management of chronic pancreatitis. Serum albumin levels, and indicator of protein caloric malnutrition, were reviewed for 34 patients. Thirty-three percent of these patients were found to have mild to moderate protein calorie malnutrition as evidence by low serum albumin levels. Enzyme therapy information was reviewed for 33 patients. Patients receiving enzyme therapy had better nutritional status based on both serum albumin levels and percent of ideal body weight. The authors conclude that

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gastroenterology nurses can be instrumental in the recognition and treatment of nutritional deficiencies in chronic pancreatitis. 3 figures. 3 tables. 4 references. •

Recurrent Acute Pancreatitis: An Algorithmic Approach to Identification and Elimination of Inciting Factors Source: Gastroenterology. 120(3): 708-717. February 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Recurrent acute pancreatitis represents a challenging clinical problem associated with significant morbidity, impairment in quality of life, and expense. The evaluation of patients with recurrent acute pancreatitis requires systematic identification or elimination of correctable inciting factors. This article provides a comprehensive yet concise overview of the causes of recurrent acute pancreatitis; a detailed review of data relevant to implicated medications, the controversial issues of pancreas divisum and sphincter of Oddi dysfunction, and the role of genetic testing; a guideline for the evaluation of patients during the initial episode of acute pancreatitis; and a consensus algorithm within which putative inciting factors may be identified and eliminated. The guidelines offered pertain only to patients with recurrent acute pancreatitis in the absence of obvious evidence of chronic pancreatitis. Future advances in the treatment of these patients will almost certainly depend on improved imaging modalities, prospective clinical trials assessing the efficacy of endoscopic and surgical intervention, a better understanding of mutations and pathophysiologic mechanisms responsible for recurrent acute pancreatitis, and the development of novel, effective preventive and therapeutic strategies. 2 figures. 6 tables. 96 references.

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Acute Pancreatitis After Abdominal Vascular Surgery Source: Journal of the American College of Surgeons. 191(4): 373-380. October 2000. Contact: Available from Journal of the American College of Surgeons. P.O. Box 2127, Marion, OH 43306-8227. (800) 214-8489 or (740) 382-3322. Fax (740) 382-5866. Summary: Retroperitoneal dissection and ischemia (lack of blood to a body part) have been proposed as risk factors for postoperative pancreatitis. This study was undertaken to determine the incidence and outcomes of pancreatitis after abdominal vascular surgery. The authors collected data on 21 patients who developed pancreatitis after abdominal vascular operations; 21 controls undergoing identical operations were also randomly identified from the authors' operative log. The incidence of pancreatitis among all patients undergoing abdominal vascular operations during the 6 year study period was 1.8 percent. Pancreatitis was diagnosed a mean of 9.8 days (plus or minus 8 days) after operation and was associated with 3 or less Ranson signs in all 21 study subjects. Although there was a trend towards longer hospitalization in the subjects, there was no difference in complication rates between the two groups. Sixteen subjects (76 percent) had no complications. Three developed severe complications, two of whom died of causes unrelated to pancreatitis. One developed a pseudocyst that resolved spontaneously. Cholelithiasis (gallstones) was a causative factor in two subjects; no cause was established in the remaining 19. There was no difference in operative details between the two groups. The authors conclude that pancreatitis is a rare and self limited complication of abdominal vascular surgery. Pancreatitis is costly and inconvenient but rarely serious after abdominal vascular operations. 3 tables. 26 references.

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Chronic Pancreatitis: Asia-Pacific Consensus Report Source: Journal of Gastroenterology and Hepatology. 17(4): 508-518. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: The current knowledge about chronic pancreatitis (CP) is limited and there is a particular lack of information about the entity known as tropical pancreatitis. A consensus working party was convened by the Trustees of the Journal of Gastroenterology and Hepatology Foundation to conduct a systematic investigation into available evidence about the epidemiology, etiopathogenesis, diagnosis and management of CP. A literature search and formal survey of international experts in the field were used to assemble reliable evidence about these issues. This review article summarizes the results of the working party's findings and presents a series of practice guidelines to improve diagnosis, investigation and treatment of patients with CP, particularly those in the Asia-Pacific region. The authors also identify areas for further research. 98 references.

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Pancreatic and Biliary Disease: Laboratory Diagnostic Tests in Acute Pancreatitis Source: Journal of Clinical Gastroenterology. 34(4): 459-462. April 2002. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: The diagnosis of acute pancreatitis (inflammation of the pancreas) depends on a combination of clinical assessment and laboratory testing. This article reviews the laboratory diagnostic tests in acute pancreatitis. Although the serum amylase is the cornerstone laboratory test used in establishing the diagnosis of acute pancreatitis, there are limitations in the sensitivity and specificity that may be important for the clinician to recognize. The serum lipase level may be especially useful in patients with alcoholinduced acute pancreatitis. A new urinary test strip that uses trypsinogen-2 may have a role in establishing the diagnosis of acute pancreatitis. In addition, several new laboratory tests and new interpretations of old laboratory tests may assist in establishing the etiology (cause) and severity of acute pancreatitis. The authors summarize important aspects of standard laboratory tests and new laboratory approaches in establishing the diagnosis, etiology, and severity of acute pancreatitis. 1 table. 36 references.

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Risk Factors for Diabetes Mellitus in Chronic Pancreatitis Source: Gastroenterology. 119(5): 1324-1332. November 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The influence of disease progression and pancreatic surgery on the appearance of diabetes mellitus in patients with chronic pancreatitis is unknown. This article reports on a prospective cohort study of 500 consecutive patients with chronic pancreatitis (alcoholics, 85 percent); patients were followed over a mean period of 7.0 years (plus or minus 6.8 years) in a medical surgical institution between 1973 and 1996. Analysis of risk factors for diabetes mellitus was performed after the exclusion of 47 patients. Patients who underwent elective pancreatic surgery (n = 231; 51 percent) were compared with patients who never underwent surgery (n = 222; 49 percent). The cumulative rate of diabetes mellitus was 83 percent (plus or minus 4 percent) 25 years

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after the clinical onset of chronic pancreatitis (insulin requirement, 54 percent). The prevalence of diabetes mellitus did not increase in the surgical group overall but was higher 5 years after distal pancreatectomy (a surgical procedure that removes 50 to 70 percent of the distal pancreas; 57 percent of the patients) than after pancreaticoduodenectomy (36 percent), pancreatic drainage (36 percent), or cystic, biliary, or digestive drainage (24 percent), without difference in the latter ones. Pancreatic drainage did not prevent the onset of diabetes mellitus. Distal pancreatectomy and early onset of pancreatic calcifications were the only independent risk factors for diabetes mellitus. The authors conclude that the risk of diabetes mellitus is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy in patients with chronic pancreatitis. This risk seems to be largely caused by progression of the disease because it increased by more than 3 fold after the onset of pancreatic calcifications. 4 figures. 4 tables. 55 references. •

Evaluation of Factors That Have Reduced Mortality from Acute Pancreatitis Over the Past 20 Years Source: Journal of Clinical Gastroenterology. 35(1): 50-60. July 2002. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: The mortality (death) associated with acute pancreatitis varies markedly in different studies, with most frequently reported mortality rates of 10 to 15 percent for all cases and 15 to 90 percent for attacks regarded as 'severe.' This article reports on a study undertaken to investigate whether there has been a reduction in mortality associated with acute pancreatitis over the past 20 years and the reasons for this reduction. The study featured the authors' 20 year prospective assessment of mortality as it relates to the severity of the disease, complications, and current therapy. The results showed that the initial reduction in mortality related to acute pancreatitis coincided with the recognition and application of the signs of severity. These signs dictated admission to intensive care unit (ICU) therapy, the intensity of ICU monitoring, and the importance of organ specific emergency therapy. Further mortality reduction in the 1990s could be attributed to either a more select study sample or earlier and more selective endoscopic or surgical debridement of infected tissue, endoscopic cyst drainage, and angiographic control of gastrointestinal bleeding. Improved nutritional support by jejunal feeding, earlier use of antibiotic therapy, gut sterilization, early endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct stones, and necrosectomy (removal of dead tissue) for noninfected necrosis have reduced the overall mortality associated with acute pancreatitis to a mean of 5 percent for all cases and 20 percent for severe cases. 1 figure. 7 tables. 44 references.

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Prevalence and Pathogenesis of Duodenal Ulcer in Chronic Alcoholic Pancreatitis Source: Journal of Clinical Gastroenterology. 35(1): 71-74. July 2002. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: The prevalence of duodenal ulcer (DU) has been considered high in patients with chronic pancreatitis; however, its pathogenesis is unclear. This article reports on a study that investigated the role of Helicobacter pylori infection in the pathogenesis of DU in this population. The study included 107 cases (97 men, 10 women) of chronic alcoholic pancreatitis (CAP) who were investigated between 1997 and 2001. Two control groups included 137 patients with DU only and 59 nonulcer dyspepsia patients. The

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results showed 15 of the 107 patients (14 percent) with CAP had active DU. There was a trend toward an association between the presence of diabetes mellitus and or steatorrhea and the occurrence of DU in patients with CAP. The rate of H. pylori infection was significantly higher in patients with CAP and DU than in those with only CAP but the rate was similar to that in patients with simple DU. There was no significant difference in prevalence of H. pylori between CAP patients without DU and dyspeptic patients. These data demonstrate that the prevalence of DU in CAP is relatively high. H. pylori infection seems to play the major pathogenic role in DU associated with CAP. 2 tables. 29 references. •

Acute and Chronic Pancreatitis Source: Practical Gastroenterology. 25(12): 47-54. December 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: There are over 100,000 hospital admissions for pancreatitis in the United States per year. Pancreatitis has numerous causes, obscure pathogenesis, and few effective treatments. This continuing education article reviews the diagnosis and management of patients with acute and chronic pancreatitis. Topics include anatomy and physiology, pathophysiology, etiology (cause), clinical presentation (symptoms), diagnosis, prognosis, treatment options, and complications, first for acute pancreatitis, then for chronic pancreatitis. The management of acute pancreatitis depends on the recognition of severity and the diagnosis and management of pancreatic necrosis (tissue death). The majority of patients will do well with conservative and supportive treatment, but necrotizing pancreatitis requires intervention due to the mortality associated with this local complication. Steatorrhea (excessive amounts of fats in the feces) in chronic pancreatitis responds to enzyme supplementation. Chronic pancreatic pain is very difficult to treat and a multidisciplinary approach is recommended. The characterization of the pain syndrome with diagnostic nerve blocks may prove to be very important at directing medical or surgical therapy. 10 figures. 4 tables. 30 references.

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Surgical Management of Chronic Pancreatitis Source: Practical Gastroenterology. 16(3): 11-13, 17-18. March 1992. Summary: This article addresses the surgical management of chronic pancreatitis. The authors discuss the indications for surgical intervention, surgical alternatives, large-duct pancreatitis, biliary obstruction, duodenal obstruction, and ascites. They note that surgery, like medical treatment, will not repair the damaged pancreas, nor will it halt the progression of the disease. However, surgery can play a very important role in management of the disease, and can significantly improve the quality of life of those affected. 6 figures. 1 table. 6 references.

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Clinical Highlights: Medical Treatment of Acute Pancreatitis Source: Hospital Medicine. 28(1): 63. January 1992. Summary: This article consists of a chart that summarizes the medical treatment of acute pancreatitis. Grouped into supportive and specific nonoperative techniques, the chart covers intravascular volume, indications for pain relief and nutrition, nasogastric suction, percutaneous peritoneal lavage, and the use of antibiotics. 1 figure.

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Diagnostic Tests in Chronic Pancreatitis Source: Practical Gastroenterology. 16(1): 23-27, 30. January 1992. Summary: This article describes the diagnostic tests used to determine chronic pancreatitis. The authors note that pancreatic calcifications and histology are the only two findings that definitively establish the diagnosis of chronic pancreatitis. Since radiologic calcification is demonstrable in only some 20 to 40 percent of patients in most series, and histology is available in only a small number of patients, the majority of patients require ancillary investigation to assist in the diagnosis. Topics include tests of pancreatic function in common use, morphologic tests, tests of endocrine function, tests of exocrine function, and etiologic tests. 4 tables. 8 references. (AA-M).

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Childhood Pancreatitis Source: American Family Physician. 59(9): 2507-2512. May 1, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This article discusses acute pancreatitis in children, a rare finding but one that is probably more common than is generally realized. This condition should be considered in evaluating children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. The most common cause of pancreatitis in childhood and adolescence is blunt trauma; child abuse should not be overlooked as a possible cause of the trauma. Other causes include metabolic and nutritional factors, alcohol abuse (particularly in older adolescents), drug effects, obstructive causes, infectious causes, and systemic causes (such as hypotension and ischemia). Recurrent pancreatitis may be familial and result from inherited biochemical or anatomic abnormalities. The mainstays of supportive treatment are fluid resuscitation, pain medication, and attention to nutritional needs. The authors note that patients with hereditary pancreatitis are at high risk for pancreatic cancer. The article includes the case of a 10 year old boy with chronic pancreatitis. 3 figures. 1 table. 15 references.

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Acute Pancreatitis in the Elderly Source: Practical Gastroenterology. 19(1): 10-12, 14-16, 21-22. January 1995. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article focuses on acute pancreatitis (AP) in the elderly. The authors note that the initial considerations in managing patients with acute pancreatitis are etiology and severity of the underlying inflammatory process. Drugs and biliary causes are the primary etiologies among elderly patients. Topics include the clinical presentation of AP in the elderly; etiological considerations; prognostic indicators, including single biochemical factors and multiple prognostic criteria; peritoneal lavage; computed tomography; therapy; development of systemic complications; pancreatic necrosis; and biliary pancreatitis. The authors conclude that laparoscopic cholecystectomy with intraoperative cholangiography and common bile duct exploration is the treatment of choice in the presence of cholelithiasis; preoperative endoscopic retrograde cholangiopancreatography (ECRP) reserved for severe cases. 5 tables. (AA-M).

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Pancreatitis: Managing a Flare-Up Source: Nursing96. 26(4): 33-40. April 1996. Summary: This article guides nurses in the care of managing patients experiencing a flare-up of pancreatitis. Topics include the degrees of inflammation of the pancreas (acute versus chronic), the anatomy and physiology of the pancreas, the causes of pancreatitis, assessing pain, symptoms, diagnostic tests and understanding laboratory findings, diagnosis and prognostic issues, setting nursing goals, managing drug therapy, managing abscesses and other complications of pancreatitis, and planning for discharge. A posttest is included with which readers can qualify for continuing education credits. 1 figure. 1 table. 3 references.

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Acute Pancreatitis: Which Route Is Better for Nutritional Support? Source: Journal of Critical Illness. 15(1): 10-11. January 2000. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Greenwich, CT 06831-0010. (203) 661-0600. Summary: This article is an entry from a regular column in which physicians answer specific clinical problems. In this column, the question concerned the nutritional management of patients with acute pancreatitis and the preferred method of nutritional support (enteral or parenteral route). The author answers by noting that the optimal route and timing of nutritional support in patients with acute pancreatitis is controversial. Deciding when to start nutritional support depends on the patient's nutritional history and severity of pancreatitis. If a patient has adequate nutritional reserve and has mild or moderate pancreatitis, it is appropriate to wait 7 to 10 days before starting either enteral or parenteral nutrition and to give intravenous fluids only. There is insufficient evidence that shows nutrition alone positively affects the outcome of acute pancreatitis. Nutritional support simply supplies fluid, macronutrients (proteins, carbohydrates, and fats) and micronutrients (electrolytes, trace elements, and vitamins) while the patient takes nothing by mouth to minimize pancreatic stimulation. After 7 to 10 days without nutrition, negative nitrogen balance occurs, increasing a patient's risk of infection. At this point, nutritional support should be started if the patient is unable to take adequate oral nutrition. The author briefly summarizes two studies that support enteral over parenteral nutrition in the management of acute pancreatitis. The author cautions that in clinical practice, however, the choice is not always that easy. Patients frequently refuse nasal tubes and often do not tolerate the feedings. The author stresses that each case needs an individualized approach and that enteral nutrition should be used whenever possible. 5 references.

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Should Elective Endoscopic Sphincterotomy Replace Cholecystectomy for the Treatment of High-Risk Patients with Gallstone Pancreatitis? (editorial) Source: Journal of Clinical Gastroenterology. 13(2): 125-128. April 1991. Summary: This article notes that endoscopic sphincterotomy is currently the procedure of choice for management of retained common bile duct stones following cholecystectomy. It also is used more frequently for choledocholithiasis with an intact gallbladder in high-risk patients and in some patients with acute gallstone pancreatitis. To avoid surgery in high-risk patients, the authors propose that an elective endoscopic sphincterotomy may be a reasonable therapeutic option regardless of whether common bile duct stones are present. A prospective trial is needed to examine this issue, since, to date, there is no literature on endoscopic sphincterotomy in the absence of

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choledolithiasis for gallstone pancreatitis in patients with intact gallbladders. 1 table. 30 references. (AA-M). •

Current Concepts in the Management of Pancreatitis Source: Drugs. 41(3): 358-366. March 1991. Contact: Available from ADIS International. Suite B-30, Oxford Court Business Center, 582 Middletown Boulevard, Langhorne, PA 19047. (215) 752-4500. ISSN: 0012-6667. Summary: This article presents current concepts in the management of pancreatitis. Topics include establishing a diagnosis, determining severity, the treating and preventing complications, and preventing recurrence. The authors note that early endoscopic sphincterotomy for patients with severe gallstone pancreatitis and ductal calculi has been reported to reduce mortality and morbidity and may prove to be an important advance. 4 tables. 42 references.

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Octreotide Treatment in Patients with Severe Acute Pancreatitis Source: Digestive Dieseases and Sciences. 45(11): 2247-2251. November 2000. Contact: Available from Kluwer Academic/Plenum Publishers. 233 Spring Street, New York, NY 10013-1578. (212) 620-8000. Fax (212) 807-1047. Summary: This article reports on a study that investigated the effect of octreotide (Sandostatin) in the treatment of severe acute pancreatitis in a case control study. Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results. The authors report on their prospective randomized study (begun in 1992) on the effect of octreotide in severe acute pancreatitis, undertaken in three hospitals in Israel. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg subcutaneously three times a day). Of 50 patients, 25 were assigned to octreotide (treatment group) and 25 to conservative treatment only (control group). The two groups were matched with regard to age, sex, etiology, and severity of the disease. The complication rate was lower in the treatment group with regard to sepsis and adult respiratory distress syndrome (ARDS). These decreases could be explained by the immunomodulatory effects of octreotide. The hospital stay was shorter in the treatment group. Two patients died in the treatment group and eight in the control group. These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis. 4 tables. 36 references.

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Acute Pancreatitis in Chronic Renal Failure Source: American Journal of Gastroenterology. 91(12): 2477-2482. December 1996. Summary: This article reports on a study to estimate the frequency and severity of acute pancreatitis (AP) associated with chronic renal failure (CRF) and to find out whether CRF causes AP. The authors studied 532 patients with a first episode of AP during the period of 1982 to 1994. Twenty-one patients had CRF; 511 patients without CRF served as controls. AP was diagnosed clinically and by elevation of amylase and lipase. CT or sonographic confirmation of diagnosis was made in all CRF patients. The cause of AP in the non-CRF group was significantly different from that seen in the CRF group. Incidence of severe AP in the two groups was 47.6 percent in the CRF group versus 21 percent in the non-CRF group. By simplified prognostic criteria, it was 38 versus 10.3 percent, respectively. Overall, CRF patients had more complications compared with non-CRF. CRF patients with severe AP had high mortality when stratified by either Ranson's or simplified prognostic criteria. The authors conclude that AP in CRF is

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frequently of unknown cause, suggesting the role of either CRF or other factors. Irrespective of cause, AP in CRF is a serious disease, associated with a high morbidity and mortality. 1 figure. 3 tables. 38 references. (AA-M). •

Pancreatitis in the Elderly Source: Journal of Clinical Gastroenterology. 19(1): 64-68. July 1994. Summary: This article reviews pancreatitis in older adults. The authors note that although acute and chronic pancreatitis in this age group are essentially the same diseases as in younger patients, some features are unique to the aged patient. Topics include incidence and etiology, clinical presentation, mortality, diagnosis, and treatment of acute pancreatitis; and the incidence and etiology, clinical presentation, diagnosis and treatment of chronic pancreatitis, including early or adult-onset chronic pancreatitis and senile chronic pancreatitis. The authors stress that complications of pancreatitis in older adults must be adequately treated to avoid malnutrition, which may seriously affect well-being and quality of life. 3 tables. 19 references. (AA-M).

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Diagnosis and Management of Acute Pancreatitis Source: American Family Physician. 62(1): 164-174. July 1, 2000. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This article reviews the diagnosis and management of acute pancreatitis, which usually occurs as a result of alcohol abuse or bile duct obstruction. A careful review of the patient's history and appropriate laboratory studies can help the physician identify the etiology (cause) of the condition and thus guide management. Serum (blood) amylase and lipase levels are still used to confirm the diagnosis of acute pancreatitis. Although not routinely available, the serum trypsin level is the most accurate laboratory indicator for pancreatitis. Ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography (ERCP) are additional modalities that can help the family physician choose the best treatment approach. Prompt identification of patients who need intensive care referral or subspecialty consultation is crucial. The APACHE II and the multiple organ system failure scales provide prognostic information at the time of admission and may be repeated daily to monitor disease progression. Therapies such as nasogastric suctioning, anticholinergics, and histamine H2 receptor blockers have not been shown to decrease symptoms or hospital stays in patients with acute pancreatitis. Systemic antibiotics have been found to improve outcome in patients with severe disease. With supportive care, most patients have a good clinical outcome. 4 figures. 8 tables. 39 references.

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Etiology and Pathogenesis of Acute Pancreatitis: Current Concepts Source: Journal of Clinical Gastroenterology. 30(4): 343-356. June 2000. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This article reviews the etiology and pathogenesis of acute pancreatitis, a disorder that has numerous causes and an obscure pathogenesis. Bile duct stones and alcohol abuse together account for about 80 percent of acute pancreatitis. Most episodes of biliary pancreatitis are associated with transient impaction of the stone in the ampulla (that causes obstruction of the pancreatic duct, with ductal hypertension) or passage of the stone through and into the duodenum. Other causes of acute pancreatitis are various

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toxins, drugs, other obstructive causes (such as malignancy [cancer] or fibrotic sphincter of Oddi), metabolic abnormalities, trauma, ischemia, infection, and autoimmune diseases. In 10 percent of cases of acute pancreatitis, no underlying cause can be identified; this condition is known as idiopathic acute pancreatitis. Intra acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis, resulting in subsequent activation of other proteases, causing the subsequent cell damage. Ischemia (fluid) or reperfusion injury is increasingly recognized as a common and important mechanism is the pathogenesis of acute pancreatitis and especially in the progression from mild edematous to severe necrotizing form of the disease. Increased intracellular calcium concentration also mediates acinar cell damage. Oxygen derived free radicals and may cytokines (e.g., interleukin 1, tumor necrosis factor alpha, platelet activating factor) are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness. The damage to pancreatic cells and blood vessels that the different enzymes and inflammatory substances cause can result in tissue hypoxia (lack of oxygen) and further cellular necrosis (cell death), resulting in a vicious circle in which more pancreatic enzymes are released and more pancreatic injury occurs. 4 figures. 2 tables. 155 references. •

Nutritional Management in Acute and Chronic Pancreatitis Source: Gastroenterology Clinics of North America. 27(2): 421-434. June 1998. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article reviews the nutritional management of patients with acute or chronic pancreatitis. Topics include determining the need and route for nutritional support, factors that affect caloric requirements, enteral access, formulas, complications of pancreatitis and how they affect nutritional therapy, outpatient therapy, and evidence that nutritional therapy makes a difference. The authors note that not all patients with acute or chronic pancreatitis require nutritional alimentation. For those whose disease is more severe, however, failure to provide nutritional support can contribute to reduced defenses, an increased rate of complications, and a prolonged hospital course. Nutritional therapy in the past was governed by the principle that the gut should rest, and stimulation of pancreatic exocrine secretion should be avoided. These concepts have been replaced by the principle that pancreatic stimulation should be reduced to subclinical levels; that gut integrity should be maintained; and that the stress response should be contained to reduce the likelihood of multiple organ failure, nosocomial infection, and mortality. 70 references.

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Role of Imaging in Acute Pancreatitis Source: European Journal of Gastroenterology and Hepatology. 9(2): 106-116. February 1997. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866 or (215) 574-2210. Summary: This article reviews the roles of ultrasound, computed tomography, and magnetic resonance imaging (MRI) in the evaluation and management of acute pancreatitis. The author notes that pancreatitis can remain localized to the pancreas and immediate peripancreatic tissues or can affect structures remote from the pancreatic bed. Thus, the imaging techniques chosen need to cover all organs and pathways likely to be affected. The author reviews the importance of imaging in the diagnosis of pancreatic necrosis, acute fluid collections, pancreatic abscess, pseudocysts, and vascular

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complications. Ultrasound is useful in the detection of gallstones and any associated compromise to the biliary tree; and in the detection of pancreatic and peripancreatic fluid collections. The role of MRI in the imaging of acute pancreatitis remains uncertain, with supporters of the technique suggesting that MRI is complementary to CT with definite advantages in certain situations. Other authors contend that the role of MRI has not been fully evaluated and currently offers no advantage over CT. The use of interventional techniques as opposed to surgical intervention is also discussed. 8 figures. 35 references (32 annotated). •

Tropical Pancreatitis Source: Journal of Clinical Gastroenterology. 35(1): 61-66. July 2002. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: This article reviews tropical pancreatitis, an uncommon cause of acute, and often chronic, relapsing pancreatitis. Patients present with abdominal pain, weight loss, pancreatic calcifications, and glucose intolerance or diabetes mellitus. Etiologies (causes) include a protein-calorie malnourished state, a variety of exogenous food toxins, pancreatic duct anomalies, and a possible genetic predisposition. Chronic cyanide exposure from the diet may contribute to this disease, seen often in India, Asia, and Africa. The pancreatic duct of these patients often is markedly dilated, and may contain stones, with or without strictures. The risk of ductal carcinoma (cancer) with this disease is accentuated. Treatment may be frustrating, and may include pancreatic enzymes, duct manipulations at endoscopic retrograde cholangiopancreatography (ERCP), octreotide (drug therapy), celiac axis blocks for pain control, or surgery via drainage or resection. The article includes a representative example case study. 1 figure. 32 references.

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Chronic Pancreatitis Source: Lancet. 350(9088): 1379-1385. November 8, 1997. Summary: This article updates physicians on the diagnosis and treatment of chronic pancreatitis. Chronic pancreatitis is an inflammatory disease in which progressive and irreversible structural changes to the pancreas result in a permanent impairment of both the exocrine and endocrine functions. The authors cover classification; etiology, including alcohol-related (70 to 80 percent of all cases of chronic pancreatitis), idiopathic, hereditary, tropical, obstructive, hyperparathyroidism, trauma, pancreas divisum, and alfa-1-antitrypsin deficiency; clinical features, including pain, pancreatic insufficiency, glucose intolerance, diabetes mellitus, and classical physical appearance; diagnostic tests, including dynamic tests and pancreatic imaging; differential diagnosis; treatment options, including for pain management, relief of obstruction, maldigestion, and malabsorption; and complications, including duodenal and bile duct obstruction, pancreatic pseudocyst, pancreatic fistula, splenic-vein thrombosis, and pseudoaneurysm formation. The authors conclude with a brief section considering when patients with chronic pancreatitis should be referred to a specialist. 4 figures. 50 references. (AA-M).

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Chronic Pancreatitis: Surgical Treatment and Procedures Source: Practical Gastroenterology. 20(9): 40, 43-44, 46, 51-52, 54-56, 59-60, 62-63. August 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected].

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Summary: This article, the eighth in a series on pancreatic disease, considers the use of surgical treatment for patients with chronic pancreatitis (CP). Surgery for chronic pancreatitis is performed for complications of the disease, for intractable pain, or when cancer cannot be excluded. The authors lament that the ideal operation, which should be simple to perform, provide longlasting pain relief, rectify the complications, avoid further endocrine and exocrine insufficiency, and have low mortality and morbidity, does not exist. Partington Rochelle decompression of the major pancreatic duct can be performed with low morbidity and mortality. Disenchantment with the operation has resulted from repeated failure to achieve sustained pain relief in half the patients who undergo it. The surgical procedures of 95 percent distal pancreatectomy was abandoned because of the high incidence of exocrine and endocrine insufficiency. From 50 to 60 percent distal pancreatectomy is applicable to a small percentage of patients with chronic pancreatitis who have ducts measuring 3 mm or less and disease limited to the body and tail of the pancreas. Pancreaticoduodenectomy, with or without pylorus preservation, is associated with sustained pain relief in 80 percent of patients, but it has not been embraced by many surgeons as their primary operation for pain relief because simpler procedures give promise of providing equivalent degrees of relief. These newer procedures, local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy, and duodenum preserving resection of the head of the pancreas, have been reported to provide sustained pain relief in about 80 percent of patients followed for an average of 37 months and 46 months, respectively. Further followup will be required to determine whether this degree of pain relief is maintained for 5 years or longer. 8 figures. 2 tables. 17 references. (AA-M). •

Acute Pancreatitis: Principles of Management Source: Practical Gastroenterology. 20(6): 26, 28, 33-36, 38-39. June 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article, the fourth in a series on pancreatic disease, presents principles of management for the care of patients with acute pancreatitis. The authors note that the treatment of these patients depends primarily on the etiology and severity of the disease. The goals of therapy are to control the inflammatory process and manage any complications that arise. The finding of complications such as respiratory impairment, sepsis, and renal failure importantly influences treatment planning. Intravascular volume repletion and maintenance is vital in acute pancreatitis because it prevents further extension of the inflammatory process. A new treatment modality that involves the use of dextran seems to provide additional benefits in this regard. Patients with acute pancreatitis should be kept fasting until the inflammatory process is deemed to be controlled. Nutritional support with parenteral feeding is indicated for patients with severe pancreatitis and those expected to fast for a prolonged period. Pain, a cardinal symptom in acute pancreatitis, can be treated with parenteral meperidine. Octreotide seems to decrease the exocrine secretory activity of the pancreas. Prophylaxis with antibiotics may be considered for patients with severe forms of the disease. A new specific cytokine antagonist, lexipafant, has been shown to be effective in decreasing complications in severe acute pancreatitis. Endoscopic treatment of severe gallstone pancreatitis in its early stages decreases the frequency of biliary sepsis. Surgical treatment is indicated in cases of infected necrotizing pancreatitis. The optimal treatment for noninfected necrotizing pancreatitis remains to be defined. Intensive medical treatment should be provided initially, with failure to respond requiring a surgical approach. 1 figure. 57 references. (AA-M).

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Surgery for Acute and Chronic Pancreatitis Source: Practical Gastroenterology. 21(1): 30-34, 37-40, 42-43. January 1997. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article, the ninth in a series on surgery of the gastrointestinal (GI) tract, describes surgery for acute and chronic pancreatitis. The authors note that the clinical management of acute pancreatitis has been evolving during the last decade because of advances in critical care and better understanding of the natural history of the disease. Bacterial infection of pancreatic necrosis now plays a crucial role in the outcome of severe acute pancreatitis. Surgical intervention is concentrated in dealing with infection of the necrosed pancreas during the acute phase. In the late phase, the indications for surgery include prolonged ventilator dependency, intractable pain, biliary disease, and complications related to the gastrointestinal tract or the pancreatic ductal system. For chronic pancreatitis, major advances include better diagnostic modalities (endoscopy, computed tomography, and magnetic resonance imaging) and newer surgical procedures (the Beger and Frey procedures). Although there is no single operation that can deal with all the complications associated with chronic pancreatitis, surgical intervention, when appropriately chosen and properly performed, can be effective in relieving pain and potentially preserving organ function. 1 figure. 1 table. 33 references. (AA-M).

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Acute Pancreatitis: Clinical Classification and Terminology Source: Practical Gastroenterology. 20(5): 8, 9-10, 12, 14, 16, 21-22, 24. May 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article, the second in a series on pancreatic disease, considers the clinical classification and terminology of acute pancreatitis. The author contends that the management of acute pancreatitis and its complications has been hampered by imprecise terminology and idiosyncratic definitions. Since optimal therapy requires accuracy in diagnosis, and since accurate diagnosis depends in turn on precise terminology, the need for an international consensus was apparent. Accordingly, a multidisciplinary group of 40 internationally recognized experts in acute pancreatitis was assembled in Atlanta, GA, in 1992 for the stated purposes of constructing a clinically based classification system for acute pancreatitis and creating a plan of management based on the new definitions. This article describes the deliberations and resulting recommendations of this symposium. The author concludes that the Atlanta Symposium's suggested classification and resulting therapeutic approach has been in prospective use for the past 5 years by authorities on acute pancreatitis all over the world and may now be recommended without reservation. One chart outlines the flow diagram for the initial management of patients with acute pancreatitis. 3 figures. 7 references. (AA-M).

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Chronic Pancreatitis: Medical Management Source: Practical Gastroenterology. 20(8): 6-8, 14-16, 18, 20-21. August 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected].

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Summary: This article, the seventh in a series on pancreatic disease, considers the medical management of patients with chronic pancreatitis. The authors classify patients with chronic pancreatitis into two categories: those with big duct disease and those with small duct disease. The diagnostic approach to and medical management of the patient with chronic pancreatitis are greatly influenced by the degree of damage to the exocrine pancreas (i.e., the size of the involved ducts). Patients with chronic pancreatitis come to medical attention primarily because of abdominal pain and or maldigestion. The cornerstone of medical management for either of these complaints is the employment of pancreatic enzyme formulations. If severe damage to the pancreas is present (big duct disease), surgical decompression of the main duct or experimental suppression of pancreatic secretion with octreotide may afford pain relief. The authors conclude by reiterating the need for the clinician to consider duct size when designing appropriate management plans for patients with chronic pancreatitis. 4 figures. 4 tables. 30 references. (AA-M). •

Chronic Pancreatitis: Selective Use of Diagnostic Laboratory Procedures Source: Practical Gastroenterology. 20(7): 54-59. July 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article, the sixth in a series on pancreatic disease, considers the selective use of diagnostic laboratory procedures in chronic pancreatitis (CP). The authors stress that the ease of diagnosing CP depends on the etiology, severity, and duration of the disease. In patients with severe CP due to alcohol, the diagnosis can be achieved through the characteristic history, plain abdominal xrays, and measurement of serum enzymes. Difficulties arise when, as in early idiopathic CP, the suspicion of CP is high but routine tests are negative. The use of more complex tests may not yield the diagnosis of CP because imaging tests (ultrasonography, computed tomography, and endoscopic retrograde pancreatography) and exocrine pancreative function tests may not yield abnormal findings until the disease is far advanced. The authors focus on providing practical points regarding the currently available tests that may be required to diagnose CP. 5 tables. 15 references. (AA-M).

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Acute Pancreatitis: Diagnosis and Evaluation Source: Practical Gastroenterology. 20(6): 8, 13-14, 16, 18, 20, 25. June 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article, the third in a series on pancreatic disease, considers the diagnosis and evaluation of acute pancreatitis. The authors note that acute pancreatitis can be diagnosed in the vast majority of patients on the basis of the history and the finding of hyperamylasemia (raised amylase level in the blood). In about 5 to 30 percent of patients, the hyperamylasemia arises from causes other than pancreatitis, thus necessitating additional investigations. If differentiation from other catastrophic surgically correctable disease is problematic, an immediate computed tomography (CT) scan or, if CT is not available, laparotomy should be performed. Once the diagnosis of pancreatitis is established, the severity of the attack should be assessed in accord with some grading schema. Severity grading derives importance because it governs prognosis, mortality, and the intensity of therapy. The scoring systems currently in use correctly predict a severe or fulminating attack with an accuracy of about 80 to 90 percent in the 20 percent of patients who present with such attacks. A CT scan should

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not be used for the sole purpose of assessing severity, as the effect of the contrast material on renal and pancreatic microcirculation is still uncertain. However, CT is essential to uncover and delineate intra abdominal complications if the attack persists. Early etiologic assessment is also important because the detection of potential causes for acute pancreatitis will influence the treatment approach, both immediately and after subsidence of the acute process. 4 tables. 6 references. (AA-M). •

Acute Pancreatitis: Another Piece of the Puzzle? Source: New England Journal of Medicine. 325(6): 423-424. August 8, 1991. Summary: This brief article describes two forms of experimental pancreatitis and hypothesizes a connection between the occurrence of pancreatic cellular injury and calcium levels. The author briefly reviews the history of research work searching for the mechanisms that trigger acute pancreatitis. The author concludes that the observation of a relation between pancreatitis and calcium administration may provide yet another clue to the still puzzling story of the pathogenesis of pancreatitis. Reference is made to another article in the same journal issue that presents research in this area. 10 references.

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Acute Pancreatitis-A Historical Update Source: Practical Gastroenterology. 16(1): 18-19. January 1992. Summary: This brief article, serving as an introduction to a series of articles on pancreatitis, presents an historical update of the condition. Topics include early references to chronic pancreatitis secondary to alcoholism, the Marseille symposium of 1963, and the non-alcohol-related forms of chronic pancreatitis (senile, hereditary, and idiopathic). 2 figures. 1 table. 14 references.

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Antibiotics Prove No Match for Necrotizing Pancreatitis Source: Gastroenterology and Endoscopy News. p. 1, 10. January 2000. Contact: Available from McMahon Publishing Group. 545 West 45th Street, 8th Floor, New York, NY 10036. (212) 957-5300. Website: www.gastroendonews.com. Summary: This news article, from a monthly newspaper for gastroenterologists, describes the use of antibiotic prophylaxis in patients undergoing surgery for acute necrotizing pancreatitis (ANP). The author notes that the data demonstrate no net benefit for this antibiotic prophylaxis. Moreover, the widespread use of imipenem (Primaxin, Merck) alters the prevalence of various microorganisms in the pancreas and results in the emergence of antibiotic resistant flora. The author briefly reports on a new study that supports this contention; 46 patients were enrolled in the study, 20 of whom received imipenem, 16 received other antibiotics, and 10 received no prophylaxis. Drug resistant organisms were found in 12 (39 percent) of the 31 infected patients. The prevalence of the pancreatic organisms in infected patients differed from the researchers' expectations. Prior studies have tended to support the use of prophylactic antibiotics to reduce the rate of pancreatic infection in patients undergoing operative procedures for ANP. 2 tables.

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Practice Guidelines in Acute Pancreatitis Source: American Journal of Gastroenterology. 92(3): 377-386. March 1997. Summary: This practice guideline reviews the basis of decisions in the management of patients with acute pancreatitis. The author notes that there are a number of important

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issues pertaining to these decisions, including the need for a consensus on terminology, the most appropriate criteria for determining severity of acute pancreatitis, choices of medical versus surgical therapy, and options for treating complications, including pancreatic pseudocysts. After a section of definitions, the author provides goals and recommendations for each category. The goals of medical therapy include supportive care, limitation of systemic complications, prevention of pancreatic necrosis, and prevention of pancreatic infection once necrosis takes place. In mild pancreatitis, fluid resuscitation and careful monitoring are the two most important components of treatment. Dynamic contrast-enhanced CT scan is recommended at some point beyond the first 3 days in severe acute pancreatitis to distinguish interstitial from necrotizing disease. In the absence of clinical improvement, guided percutaneous aspiration should be performed to distinguish infected necrosis from severe sterile necrosis. Infected necrosis requires surgical debridement; severe sterile necrosis can usually be treated medically. Asymptomatic pseudocysts require no specific treatment. Symptomatic pseudocysts can be decompressed by surgical, radiologic, or endoscopic methods. 1 figure. 6 tables. 38 references. (AA-M). •

Management of Acute Pancreatitis: A Critical Assessment as Dr. Bockus Would Have Wished Source: American Journal of Gastroenterology. 90(5): 696-703. May 1995. Summary: This presentation, from the 1994 World Congress of Gastroenterology, reviews the management of acute pancreatitis. Topics covered include etiology and pathogenesis; terminology; severity grading; initial management of acute pancreatitis; peritoneal lavage; necrosis and infection; and biliary pancreatitis. The author focuses on some selected features and certain collateral factors that subtly or overtly influence the nature, breadth, and intensity of the therapeutic measures. 6 figures. 67 references. (AAM).

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Clinical Update: Management of Acute Pancreatitis Source: Journal of Gastroenterology and Hepatology. 12(3): 189-197. March 1997. Contact: Available from Blackwell Science Pty Ltd. P.O. Box 378, Carlton, Victoria 3053, Australia. Phone: 61 3 9347 0300; Fax: 61 3 9347 5001; E-mail: [email protected]. Web site: http://www.blacksci.co.uk. Summary: This review article considers the management of acute pancreatitis. The authors follow the clinically based classification system adapted at an international symposium in Atlanta in 1992. Acute pancreatitis refers to an acute inflammatory process of the pancreas, with variable involvement of other regional tissues or remote organ systems. The authors emphasize the importance of confirming the diagnosis and establishing the etiology. Improved methods of assessing the biliary tree may reduce the number of patients regarded as having idiopathic pancreatitis. Detailed clinical and laboratory protocols, designed to assess severity, have no major advantage over clinical assessment. The contrast-enhanced computed tomography (CT) scan is important to assess the degree of pancreatic necrosis and to detect local complications. The treatment of pancreatitis continues to be largely supportive. However, controlled studies support the use of antibiotics in severe acute pancreatitis and indicate a possible role for the use of octreotide and antioxidants. The place of endoscopic and surgical intervention is becoming better defined. Once an attack has passed, further investigation is often required in an attempt to prevent further episodes of inflammation. 1 figure. 2 tables. 99 references. (AA-M).

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Chronic Pancreatitis: Diagnosis, Classification, and New Genetic Developments Source: Gastroenterology. 120(3): 682-707. February 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: This review article focuses on the definitions and classification of chronic pancreatitis, on structural and genetic analysis, and on risk factors. Recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. The authors maintain that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography (CT) remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging (MRI) are considered. Once chronic pancreatitis is diagnosed, proper classification become important. Major predisposing risk factors to chronic pancreatitis may be categorized as either toxic metabolic, idiopathic (unknown), genetic, autoimmune, recurrent and severe acute pancreatitis, or obstructive (TIGAR O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end stage chronic pancreatitis. 8 figures. 5 tables. 242 references.

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Gallstone Pancreatitis: Choosing and Timing Treatment Source: Postgraduate Medicine. 89(2): 123-129. February 1, 1991. Summary: Why the passage of small gallstones sometimes causes pancreatitis is still unclear, but the condition leads to life-threatening multisystem dysfunction in some people. This article notes that surgical removal of stones or the gallbladder is often necessary to prevent complications and recurrence. The timing of surgery is dictated by serum enzyme levels and liver function test results as well as by the patient's condition. Whether surgery or endoscopic sphincterotomy is preferable as primary therapy for gallstone pancreatitis remains unresolved. The authors illustrate diagnosis of the disorder with two representative case reports and also address treatment issues. 2 figures. 3 tables. 24 references.

Federally Funded Research on Pancreatitis The U.S. Government supports a variety of research studies relating to pancreatitis. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable

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

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

Project Title: 13CHIOLEIN BREATH TEST--NONINVASIVE MEASUREMENT OF PANCREATIC EXOCRINE FUNCTION Principal Investigator & Institution: Toskes, Phillip; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001 Summary: The purpose of this study is to show that the Hiolein breath test is a simple, safe and reliable test to diagnosis patients with chronic pancreatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A PHYSICAL ACTIVITY & NUTRITION INTERVENTION IN HIV Principal Investigator & Institution: Smith, Barabara A.; None; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2005 Summary: Although the use of potent antiretrovirals has improved mortality and morbidity associated with HIV-1 infection, new constellations of side effects continue to challenge nurses and other providers. One new syndrome associated with the antiretroviral therapy, lipodystrophy or fat redistribution, includes peripheral wasting, central fat accumulation, elevated blood lipids, glucose and insulin and places patients at risk for cardiovascular disease, diabetes, pancreatitis and may influence adherence to drug therapy; thus, the management of troubling side effects and symptoms such as lipodystrophy has taken on new importance and underscores the need to examine strategies that may attenuate or alleviate these side effects/symptoms. Subsequent work will need to focus on the prevention of the syndrome once strategies for managing the syndrome(s) have been identified. The purpose of the proposed study is to examine the effects of a 16-week integrated intervention designed to improve body composition, blood lipids and metabolic variables in HIV-1 infected individuals who are enrolled in NIH funded clinical trials of highly active antiretroviral therapy (HAART) and who are experiencing lipodystrophy. The intervention consists of three major components: physical activities intended to increase cardiorespiratory endurance, physical activities that will enhance strength, flexibility and increase cross-sectional area of muscle, and a nutrition component. Each component of the intervention is intended to improve some aspect of the lipodystrophy syndrome and is consistent with the Healthy People 2010. This experimental study will use a 2-group design with subjects in the experimental group (n=42) encouraged to accumulate 30 minutes of physical activity most if not all days of the week and set measurable dietary goals with the dietitian. Subjects in the control group (n=42) will maintain usual activity and usual diet for 16 weeks and then enter the intervention phase of the project. Subjects will be recruited from the ALLRT

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protocol or FRAM study at the UAB Outpatient HIV Clinic. A two by two, mixed model ANCOVA will be used to test study hypotheses related to body composition, blood lipids, glucose, insulin and C-peptide. Data from the study will be used to develop evidence-based guidelines for advanced practice nurses, dietitians, physicians and other health care providers to assist patients in managing lipodystrophy associated with HIV1 therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACUTE PANCREATITIS Principal Investigator & Institution: Steer, Michael L.; Professor of Surgery; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-JUL-1982; Project End 31-JUL-2003 Summary: (Adapted from investigator's abstract) Currently available evidence indicates that digestive enzyme zymogens such as trypsinogen become prematurely activated within acinar cells of the pancreas during the early stages of acute pancreatitis. Activated digestive enzymes are believed to cause cell injury leading to acinar cell death and pancreatitis. The proposed project will pursue the following specific aims: 1) to define the mechanisms responsible for premature activation of zymogens within the pancreas and the role of those activated digestive enzymes in the evolution of acute pancreatitis; and 2) to determine if the type of acinar cell death (ie, necrosis or apoptosis) during acute pancreatitis regulates the severity of that acute pancreatitis. The specific aim #1 studies will build on the observation that infusion of a supramaximally stimulating dose of the CCK analog caerulein causes intrapancreatic activation of trypsinogen as well as pancreatitis in rats. Furthermore, cathepsin B mediated activation of trypsinogen occurs when isolated acini are incubated in vitro with supramaximally stimulating concentrations of caerulein. In the proposed studies, the intracellular location of trypsinogen activation, the cellular events involved in trypsinogen activation, and the mechanism by which trypsinogen activation leads to cell injury will be determined. In the specific aim #2 studies, several models of experimental pancreatitis in laboratory animals (mice, rats, opossums) will be utilized to evaluate the possibility that apoptosis minimizes the severity of pancreatitis. The mechanisms underlying this phenomenon will be examined and the potential value of treating established pancreatitis by inducing apoptosis will be evaluated. Successful completion of these proposed studies will provide important new insights into the cellular basis for acute pancreatitis and identify methods of either preventing or minimizing the severity of this frequently lethal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADENOSINE IN TRAUMA AND SEPSIS Principal Investigator & Institution: Hasko, Gyorgy; Surgery; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: Multiple organ failure (MOF) is the cause of 50 percent to 80 percent of all deaths in surgical intensive care units. MOF is documented to occur after a number of diverse clinical conditions, including mechanical and thermal trauma, pancreatitis and shock. In a large subgroup of patients, secondary infections serve to trigger the development of MOF, which is related to the development of an excessive compensatory anti-inflammatory reaction (CARS) and a generalized immunosuppressive state. CARS is characterized by several changes in the patients'

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immune phenotype. Two of the most important of these immune-phenotypic changes are a shift in T helper (Th) cell population from a Th1 to a Th2 response and shift in the macrophage phenotype from a proinflammatory to an anti-inflammatory one. This shift in the macrophage phenotype is characterized by a decrease in the production of IL-12 and an increase in the production of IL-10. Neither the signals nor mechanisms responsible for the development of this altered immune phenotype have been fully elucidated. Recently, it has been proposed that this immunosuppressed state may be secondary to the excessive release of a variety of mediators including catecholamines and glucocorticoids by activation of the stress system. In addition, it appears that adenosine (ADO), another stress mediator released excessively during CARS, could also contribute to the immune paralysis seen in CARS, since ADO appears to potentiate the development of an immune compromised state. Using an anti-CD3- stimulated mouse spleen cell system, we have recently discovered that extracellular ADO augments the production of the Th2 cytokine IL-4, whereas it reduces the production of the Th1 cytokine interferon-gamma. In addition, we have obtained evidence that ADO enhances IL-10 and decreases IL-12 production by immunostimulated macrophages. Thus, we will investigate the hypothesis that high extracellular concentrations of ADO may contribute to the deleterious immune hyporesponsiveness observed in patients with CARS. Because ADO exerts its biological effects by binding to any of 4 specific cell surface receptors, we also hypothesize that ADO shifts the immune response from a proinflammatory to an anti-inflammatory one through the activation of certain ADO receptors present on T cells and macrophages. We will test these hypotheses both in vitro using T cell and macrophage systems as well as in vivo using the mouse cecal ligation and puncture model of MOF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALCOHOL REDUCTION IN MEDICAL ILLNESSES:HCV AS PROTOTYPE Principal Investigator & Institution: Dawson, Neal V.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Alcohol use is discouraged or contraindicated for patients with a variety of medical illnesses. For many diseases directly caused by alcohol, the use of alcohol may be associated with recurrent symptoms shortly after its consumption, e.g., pancreatitis or gastritis, and the prohibition against alcohol is straightforward. However, for many chronic diseases, the use of alcohol is not associated with any short-term symptoms or sequelae. The course of these chronic diseases (or their treatments) among non-abusing/nondependent patients can be adversely affected by even moderate alcohol use, e.g., chronic hepatitis, (nonalcoholic) cirrhosis, severe diabetes, or the use of the 'blood thinner', warfarin. Chronic Hepatitis C virus (HCV) infection is a prototypical example of a disease in which alcohol use tends to cause no symptoms. Even moderate chronic alcohol use can be associated with an increased likelihood of cirrhosis and liver cancer. HCV infection rates and prognosis are related to alcohol use in multiple ways. Alcohol use during HCV treatment is associated with a decreased likelihood of viral clearance. Long-term alcohol use may increase the proliferation of HCV and the associated liver damage even with moderate alcohol consumption. Greatly reducing or eliminating alcohol use may importantly enhance the prognoses of patients, even if they are not candidates for specific HCV treatments. Despite having diagnoses that warrant abstinence from alcohol, many patients continue to drink alcohol. Little is known about why patients continue to consume alcohol in the

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face of diagnoses that warrant a reduction in use or abstinence. The current study is designed to determine factors that lead to continuing alcohol intake among alcohol nonabusing/nondependent patients who are advised to stop drinking by health care providers. In Phase 1, focus groups (patients and providers) will be used to discover issues that may be associated with continued drinking. In Phase 2, questionnaire items will be developed based on the data gleaned from Phase 1. The potential pool of items will be administered to 10 patients per item and factor analyzed. In Phase 3, the items retained from the pool of potential items will be used to create a questionnaire that will be tested for its ability to predict alcohol reduction or cessation. Since alcohol use is common in the U.S. and since most patients who currently have HCV are not candidates for treatment, abstinence from alcohol use represents a major opportunity to prevent a decline in the health and quality of life of patients with HCV and similar diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALCOHOL SENSITIZES THE PANCREAS FOR CK INDUCED PANCREATITIS Principal Investigator & Institution: Pandol, s; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001 Summary: The broad long-term objective of the work described in this application is to determine the molecular mechanisms responsible for the exocrine pancreatic disorders caused by ethanol. The work proposed is designed to determine the effect of an ethanolcontaining diet on the factors that mediate pancreatitis. Our hypothesis states that a ethanol diet alone or in combination with a low dose of cholecystokinin-octapeptide (CCK-8) infusion results in activation of transcription factors involved in regulating the expression of pro-inflammatory cytokines and chemokines. These cytokines/chemokines, in turn, mediate the inflammatory and cell death responses that are the hallmarks of pancreatitis. Using a rat model of continuous infusion of an ethanol-containing diet, we proposed the following specific aims: 1. Determine the effect of the ethanol diet with and without the CCK-8 infusion on activation of transcription factors (i.e., NF- kappaB and P-1) that regulate cytokine/chemokine production in the pancreas and inflammatory and cell death responses. 2. Determine the mechanism(s) of NF-kappaB and AP-1 activation in the pancreas caused by the ethanol diet in the presence and absence of the CCK-8 infusion. 3. Determine the effect of the ethanol diet with and without the CCK-8 infusion on the expression and regulation of specific cytokines/chemokines and their role in mediating inflammatory and cell death responses in pancreatitis. 4. Determine the effect of the ethanol diet with and without the CCK-8 infusion on intrapancreatic trypsin activation and the mechanism(s) of these effects on intrapancreatic trypsin activation. Measurements. to accomplish these goals will include serum amylase and lipase, pancreatic weight, pancreatic necrosis, apoptosis, vacuolization, neutrophils and macrophages using histologic techniques: pancreatic trypsin activation; transcription factor activation using gel shift assays; and expression of cytokines/chemokines using RT-PCR. Western blot analysis, immunocytochemistry and bioassay. The results of the studies described in this application will be elucidation of the mechanism of ethanol's effects in pancreatitis that can be used to design strategies for therapeutic interventions and clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AMYLIN AND ITS RELEASING FACTOR IN THE EARLY DIAGNOSIS OF PANCREATIC CANCER Principal Investigator & Institution: Adrian, Thomas E.; Professor; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001; Project Start 25-MAR-1999; Project End 31-JAN-2003 Summary: Pancreatic cancer is associated with profound insulin resistance, resulting in diabetes in up to 80% of patients. This metabolic abnormality is tumor dependent and disappears after tumor resection, despite the loss of islets. Amylin is a pancreatic hormone that inhibits muscle glycogen synthesis and reduces food intake. In most pancreatic cancer patients, amylin levels are elevated in the fasting state. Even though diabetes may not be a major problem for the management of patients with pancreatic cancer, measurement of amylin may be a valuable marker for the early diagnosis of the disease, at least in a proportion of patients. Furthermore, the increased amylin levels appear to result from stimulation of peri-tumoral islets by a tumor-derived peptide (amylin releasing peptide of ARP). It is likely that, compared with amylin, circulating ARP levels are elevated in an even higher proportion of pancreatic cancer patients. The major goals of this proposal are as follows: 1. To investigate the specificity of elevated circulating amylin in pancreatic cancer, by investigating patients with pancreatitis, biliary obstruction, newly diagnosed diabetes, pancreatic cancer or other malignancies. 2. To purify and sequence ARP and develop a radioimmunoassay to measure this peptide. 3. To establish whether ARP is a better marker for pancreatic cancer than amylin, by measurement in the above groups of patients. 4. To determine the value of amylin and ARP as early indicators of pancreatic cancer, by measuring the peptides in families with a high risk of developing the disease, and by measuring them in samples from pancreatic cancer patient collected several years prior to their cancer diagnosis. This study may aid in the development of an early screening technique for detecting pancreatic cancer at an early, curable stage. In addition, it will improve our understanding of the role played by the islets in this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTI-INFLAMMATORY PAF ACETYLHYDROLASE IN LUNG INJURY Principal Investigator & Institution: Howard, Katherine M.; Assistant Professor; Biochemistry; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: Plasma-type platelet-activating factor acetylhydrolase is a distinct Ca+2independent phospholipase A2 enzyme specific for the inactivation of platelet-activating factor (PAF) and PAF- like phospholipids. Thus, PAF acetylhydrolase plays a crucial role in inactivating a potent inflammatory mediator implicated in the initiation and propagation of acute lung injury. This anti- inflammatory property of PAF acetylhydrolase has lead to the therapeutic investigation of PAF acetylhydrolase in a wide range of inflammatory diseases including asthma, Adult Respiratory Distress Syndrome, diabetes, pancreatitis, and vascular and heart disease. The objective of the proposed research is to investigate the cellular and molecular mechanisms involved in the expression and regulation of PAF acetylhydrolase in rat models of acute lung injury. Lung tissue PAF acetylhydrolase expression is dramatically increased in response to in vivo inflammatory challenge. Three closely related Specific Aims will lead to the localization and characterization of PAF acetylhydrolase- expressing cells; the

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elucidation of the mechanisms involved in PAF acetylhydrolase up-regulation; and the determination of the physiological consequences of increased PAF acetylhydrolase in resolving and limiting lung injury. First, a detailed localization and characterization of PAF acetylhydrolase in normal lung and in response to lung injury will be performed. These experiments in whole animals will explore the differential expression of PAF acetylhydrolase in resident lung macrophages and granulocytes. Granulocytes, predominately comprised of neutrophils, appear to have the capacity to deliver this potent anti-inflammatory agent to sites of inflammation. Second, the involvement of PAF, the PAF receptor, and STAT transcription factors in PAF acetylhydrolase upregulation will be examined. These experiments will determine the effects on PAF acetylhydrolase expression resulting from the administration of PAF and PAF receptor antagonists and in mice genetically lacking the PAF receptor. Third, the physiological consequences of up- regulated PAF acetylhydrolase expression in lung injury will be investigated by assessing the in vivo PAF-degrading capacity of the compromised lung and determining the effects on the lung inflammatory sequelae in response to exogenous PAF acetylhydrolase administration. Through the logical design of the proposed studies, novel and important information will be gained that will significantly advance our understanding of the cell biology of this important anti-inflammatory enzyme. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APOPTOSIS AND NECROSIS IN PANCREATITIS Principal Investigator & Institution: Gukovskaya, Anna S.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Inflammation and parenchymal tissue damage are hallmarks of pancreatitis. In particular, severe necrosis is a major complication of the disease. Over the past decade, significant progress has been achieved in understanding the mechanisms of the inflammatory response of pancreatitis. In contrast, very little is known about the mechanisms of pancreatic acinar cell death. Mechanisms of necrosis are largely unknown. Key signals mediating apoptosis have been established; however, their roles in disease processes remain obscure, and they have not been investigated in pancreatitis. The role of cell death pathways in pathologic trypsin activation, an important marker of tissue damage in pancreatitis, has not been explored. Our preliminary data indicate that key necrotic and apoptotic mechanisms: poly (ADPribose) polymerase (PARP), mitochondrial dysfunction, caspases (specific cysteine proteases), and the transcription factor NFkappaB are activated in experimental models of pancreatitis and in pancreatic acinar cells stimulated with cholecystokinin (CCK). For the present application, we hypothesize that in pancreatitis, necrotic and apoptotic signaling pathways are interrelated. Activation of PARP and mitochondrial deenergization leads to ATP depletion and necrosis. On the other hand, effector caspases mediate apoptosis and limit necrosis by inactivating PARP and trypsin. NFkappaB negatively regulates effector caspases and, thus plays an anti-apoptotic role in pancreatitis. Thus PARP, mitochondrial dysfunction, caspases, and NFkappaB play central roles in determining the balance between apoptotic versus necrotic type of acinar cell death and the severity of pancreatitis. We propose the following specific objectives for the present application: 1). Determine the role of PARP in necrosis and apoptosis in experimental pancreatitis and in vitro, in pancreatic acini stimulated with CCK. 2). Determine the role of mitochondrial dysfunction in necrosis and apoptosis in experimental pancreatitis and in vitro, in pancreatic acini stimulated with CCK. 3)

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Determine the role of caspases in necrosis, apoptosis, and trypsin activation in experimental pancreatitis and in vitro, in pancreatic acini stimulated with CCK. 4). Determine the role of NFkappaB in necrosis and apoptosis in experimental pancreatitis and in vitro, in pancreatic acini stimulated with CCK. Measurements to achieve these goals will include measures of pancreatitis, morphologic characterization of apoptosis and necrosis, intrapancreatic activation of caspases and trypsin, cytochrome c release, mitochondrial membrane potential, ATP levels, and NFkappaB activation by using Western blot and gel shift analyses, enzymatic and fluorimetric assays. The result of the experiments in the proposed specific objectives will be delineation of key molecular mechanisms regulating necrosis and apoptosis in acute pancreatitis, which will lead to novel therapeutic strategies to treat the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APPROACHES TO THE STUDY OF PANCREATIC REGENERATION Principal Investigator & Institution: Raper, Steven E.; Associate Professor; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from Applicant's Abstract): This proposal seek to extend the knowledge already accumulated about recombinant adenoviral gene transfer to the pancreas, and to use this knowledge to study two fundamental problems of pancreatic biology-pancreatic regeneration and islet morphogenesis. The experiments outlined below were planned based on four overarching hypotheses which have been developed based on the preliminary work done in the laboratory of the PI, as well as extensive review of the literature: 1.) The transient gene expression seen in pancreatic cells transduced with recombinant adenoviruses can be overcome by further study of the mechanisms involved; 2.) Host immunomodulation is one promising strategy for establishing long-term gene expression; 3.) Recombinant adenoviruses can be engineered to express genes involved in pancreatic growth and used as probes to elucidate the biology of regeneration; 4.) Recombinant adenoviruses will be useful in designing innovative strategies to study islet morphogenesis, and ultimately target the islets for gene therapy in vivo. The following Specific Aims will be undertaken in the conduct of this grant: 1.) To study the interaction of recombinant adenoviral vectors with the pancreas of immunocompetent/immunodeficient mice; 2.) To study the interaction of recombinant adenoviral vectors with the pancreas of immunodeficient mice, and to test innovative approaches to prolonging viral transgene expression in pancreata transduced into immunocompetent mice; 3.) To study the effect of physiologic perturbations (streptozotocin, acute pancreatitis, pancreatic resection) on stability of pancreas directed gene transfer; 4.) To study the effect of recombinant adenoviruses encoding the pancreatic growth genes regA and regB as well as hepatocyte growth factor (HGF) in attempts to stimulate pancreatic regeneration; 5.) To target beta cells of the islets of Langerhans by promoting long-tern gene expression and observing transit of transgene expressing cells from the periphery. The information learned from these studies will be important in understanding the biology of pancreatic regeneration and islet morphogenesis. The work will also allow a deeper understanding of pancreatic immunology and the development of innovative strategies for pancreas and isletdirected gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAR FUNCTION IN VIRUS TROPISM AND CELL-CELL CONTACT Principal Investigator & Institution: Bergelson, Jeffrey M.; Assistant Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Coxsackie B viruses (CBV) and Adenoviruses (Ads) are the major causes of viral myocarditis, and CBV are implicated in the pancreatitis and diabetes. All CBV and many Ads initiate infection by attachment to the coxsackievirus and adenovirus receptor (CAR), a cell surface glycoprotein whose physiologic function has not been defined. This proposal concerns both CAR's role in virus tropism and its physiologic function. We recently found that CAR is a functional component of the epithelial cell tight junction, a specialized intercellular contact that serves as a barrier to the paracellular solute movement. On polarized epithelial cells, CAR is sequestered in tight junctions; consequently, epithelial monolayers resist infection by both CBV and Ads. Some CBV also attach to a second receptor, DAF, a molecule whose role in infection has remained poorly understood. Preliminary data indicate that while DAF may alter the route by which virus enters a cell, it does not trigger conformational changes in the virion essential that are essential for infection. However, DAF is targeted to the apical surface of polarized cells, and a DAF-binding CBV variant efficiently infects epithelial monolayers; we propose that interaction with DAF provides a mechanism for virus infection at epithelial and mucosal surfaces. In the first series of proposed experiments, we will determine the functions of CAR and DAF during infection, define the route of virus entry for CAR-binding viruses and DAFbinding variants, and test the hypothesis that attachment to DAF permits CBV to cross epithelial surfaces In a second series of experiments we will define CAR's function in CBV pathogenesis in an in vivo model. In human tissues, CAR mRNA is most highly expressed in the heart and pancreas, the major CBV target organs both in humans and in animal models of infection. We will use a conditional gene targeting strategy to determine whether tissue-specific CAR expression is essential for CBV infection, and for virus-induced pathology in the heart and pancreas. In a final group of experiments we will explore CAR's physiologic functions. We have found that CAR is both a structural and functional component of the tight junction, that CAR interacts with the major junctional protein ZO-1, and that homotypic interactions between CAR extracellular domains mediate cell adhesion and contribute to junctional integrity. We will determine the structures involved in CAR-mediated homotypic adhesion, and define CAR' s interactions with other proteins important for junction formation and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CENTER FOR ALCOHOLIC LIVER AND PANCREATIC INJURY Principal Investigator & Institution: Tsukamoto, Hidekazu; Professor of Medicine & Pathology; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The proposed Alcohol Research Center constitutes the first Los Angeles citywide Center of Excellence devoted to Studies on Alcoholic Liver and Pancreatic Injury. The Center is created through consolidation of existing collaborative and interactive programs among the established investigators at USC and UCLA. These investigators are unified by the Center's theme, "Elucidation of the mechanisms by which ethanol primes and sensitizes the liver and pancreas for injury", which illustrates their shared research philosophy and goal. To pursue this theme, the Center will solidify the

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integration and cross-utilization of the unique and specialized expertise that each participating investigator will contribute to the Center such as animal models, morphology, glutathione homeostasis, oxidative stress, cytoskeletal biology, nonparenchymal liver cell biology, molecular virology, pancreatic acinar cell biology, and signal transduction. The Center will also catalyze cross-utilization of complementary resources by our Center and other existing Centers of Excellence on both campuses (USC Center for Liver Disease, USC Hepatitis C Cooperative Research Center, USC Norris Comprehensive Cancer Center, UCLA CURE Digestive Disease Research Center) to promote technical and academic synergism and to achieve integrated dissemination of educational activities. In addition to the city-wide approach and the unified Center's theme, the Center is unique in that the intragastric ethanol infusion model (IEI model) serves as an integral component which supports most of the enter research activities directed toward the theme. The center will also be the first to offer the animal or tissue sharing program for the IEI model to non-Center investigators. It is our Center's ultimate goal to establish effective preventive and therapeutic modalities for alcoholic liver and pancreatic diseases via mechanistic delineation of ethanol primes and sensitized these organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION AND SORTING OF ZYMOGEN GRANULE PROTEINS Principal Investigator & Institution: Lowe, Anson W.; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-FEB-1991; Project End 31-JAN-2005 Summary: (provided by applicant): The exocrine pancreas is responsible for the synthesis and secretion of digestive enzymes into the intestine. The acinar cell is responsible for the pancreas' exocrine functions and can be characterized as a polarized secretory epithelia. Digestive enzyme secretion is also regulated and can be stimulated with acetylcholine and cholecystokinin. The key subcellular organelle responsible for regulated secretion in the acinar cell is the zymogen granule; a secretory vesicle that stores and concentrates digestive enzymes until secretion is stimulated. The focus of this project has been the characterization of zymogen granule membrane proteins as a means toward understanding the mechanisms underlying the formation of secretory granules and the targeting of proteins to the regulated secretory pathway. GP2 is the dominant protein in the zymogen granule membrane and accounts for 35 percent of the total granule membrane protein. In vitro studies have demonstrated that GP2 is able to aggregate with other exocrine regulated secretory proteins in acidic conditions designed to mimic the trans-Golgi network and immature secretory granule where sorting occurs. GP2 is initially bound to the membrane through a glycosylphosphotidylinositol linkage, which by itself confers membrane protein sorting to the apical plasma membrane. Because GP2 exhibits binding to the soluble digestive enzymes within the granule and contains a sorting determinant for the apical plasma membrane, it is likely that the protein plays a significant role in sorting digestive enzymes into the zymogen granule and the regulated pathway. The goal of this application for the next funding period is to define GP2's function. Transgenic knockout techniques will be employed to produce a mouse with a GP2 null allele. Because GP2 is specifically expressed in the pancreatic zymogen granule and the exocrine pancreas is not functional until after birth, it is unlikely that an embryonic lethal will result from the mutation. Thus preparations have been made to analyze the resultant mutant mice using biochemical, morphological, and physiological approaches. Electron microscopy will be used to study GP2's role on the

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formation of the zymogen granule. Primary pancreatic cultures will be used to study the integrity of the regulated secretory pathway in the mutants. To establish that any resultant phenotypes are truly secondary to the GP2 null mutant, preparations have been made for the reconstitution of wild-type GP2 in primary pancreatic cultures using adenovirus mediated gene delivery. Adenovirus expression of a variety of mutant GP2 constructs will be used to identify important functional domains in the protein. Last, studies will be performed on the effects of the GP2 mutation in experimentally induced pancreatitis. The model we propose to generate will provide important information on GP2 biology and may also provide potential models for human acute and chronic pancreatic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--GHC POPULATION AND SURVEILLANCE Principal Investigator & Institution: Chu, Susan; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001 Summary: The Overall goal of this Core is to support individual projects and overall objectives by identifying and recruiting patients for participation in Program Project Studies, by collecting gastrointestinal cancer tissues from cases that arise in a population of approximately 400,000 enrollees, and by enhancing the ability of Program Project investigators to conduct longitudinal studies in colon and pancreas cancer. Through the Center for Health Studies, the GHC Population Core will facilitate access to a health care delivery system that has distinct advantages as a setting for translational research that include a large defined patient population and a rich array of information systems; established programs in cancer screening with linkage to risk factors and pathologic outcomes; and experience in the design, conduct, and analysis of intervention and observational studies of cancer prevention, control and treatment. The specific aims of the GHC Population Core are: 1) To identify and collect specimens from patients with chronic pancreatitis, pancreatic cancer, and colon cancer for proposed projects 1 and 4; 2) To recruit patients undergoing colonoscopy and collect risk factor data, fecal and blood samples, and biopsy results, and tissue specimens for longitudinal studies of colon cancer risk and development; and 4) To establish a surveillance system to monitor changes in gastrointestinal cancer incidence, morbidity, and mortality in our defined population. The GHC Population Core will build and maintain a retrospective registry with linked pathology results of more than 9800 patients who underwent colonoscopy between 1991 and 1996 and will add risk factor data for the anticipated 4800 patients who will be colonoscopied during the project period. Group Health Cooperative (GHC) is a staff-model managed care organization that serves over 400,000 enrollees in the western Washington Puget Sound region. The GHC Population Core will operate within the GHC Center for Health Studies, a research organization dedicated to the conduct of studies that contribute to scientific knowledge in the public domain and to the quality of health care at GHC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--PANCREAS TUMOR SPORE TISSUE BANK Principal Investigator & Institution: Bridge, Julia; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001

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Summary: All projects in this SPORE will use human specimens for translational research directed at reducing the incidence and mortality of pancreatic cancer. In order to provide the necessary specimens, a Pancreas Tumor SPORE Tissue Bank will be developed in cooperation with and under the auspices of the University of Nebraska Medical Center (UNMC) Tumor Bank. The guidelines and protocols for collecting specimens established by the UNMC Tumor Bank and the Institutional Review Board will be followed for the SPORE proposal. This core facility will store normal, benign (i.e. acute and/or chronic fibrosing pancreatitis) and malignant pancreatic tissues (including both primary and metastatic pancreatic carcinomas) and peripheral blood lymphocytes, plasma and serum from patients with pancreatic malignancies. The bank will also coordinate collection and storage of pancreatic ductal secretions and peritoneal washings. Cytogenetic analysis will be performed on all malignant lesions when possible. The core will include a mechanism for database management and specimen distribution. A uniform system of prioritization of requested materials would be defined and used by the Pancreas Tumor SPORE Tissues Bank oversight committee. This core facility is intended to benefit the specific research activities of the SPORE as well as the research activities of other scientists within and outside of UNMC who are concentrating on translational research issues. Additionally, tissues will be available for distribution through NCI supported tissue networks in national prioritization. Only specimens obtained from clinically indicated surgeries after all other diagnostic procedures have been performed will be submitted to the Pancreas Tumor SPORE Tissue Bank for translational research. The specimens would other wise be discarded or disposed of. Eligible patients will have the opportunity to participate by submitting written informed consent. There will be no risk to the patient or compromise to the patient's care, since all of the procedures performed would be performed for diagnostic reasons regardless of the SPORE. Members of the pathology department and the clinical departments are participants in the individual research projects and thus, also contribute to the Core for maximal and effective accumulation of satisfactory specimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--PATIENT/BIOSTATISTICS FACILITY Principal Investigator & Institution: Corey, Mary; Associate Professor; Hospital for Sick Chldrn (Toronto) 555 University Ave Toronto, Timing: Fiscal Year 2001 Summary: The Patient/Biostatistics Core provides an overall structure for maintaining and connecting all the available patient data related to mutations in the CFTR gene, generates regular summaries for the design and analysis of experiments and observational studies. Core activities will include: integration of new clinical and scientific data into the Toronto CF Database; support for the database on male infertility patients, who comprise the largest identified group of an expanded spectrum of patients affected by mutations in the CFTR gene; creation of data files and analytic strategies to study other atypical phenotypic groups related to CFTR, such as young patients with pancreatitis and adults with chronic lung disease; provision of clinical profiles for individual patients and patient groups to enhance the planning or interpretation of scientific experiments; statistical analysis of core and project data; and timely statistical consulting for the design and interpretation of experiments. A particular focus in the next period will be the acquisition and support of new and developing software for linkage and association analysis of complex genetic traits. SAS software is used for most data management and statistical analysis, including longitudinal regression and survival regression. Other computer programs used for specific purposes include

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SPLUS (for graphics and sophisticated statistical estimation); Mapmaker/Sibs, SAGE, and GAP (for genetic linkage and association analysis); DBMS/COPY and ConversionsPlus for converting and transferring files between different systems. Increasingly, different types of laboratory data will be retrieved directly from other computer systems within the hospitals, necessitating increased levels of quality control and validity checking to ensure appropriate record linkage and to preserve the confidentiality of identified patient data. Core support will ensure that scientists have access to the most appropriate patient information and material to design experiments, and that research hypotheses and results are related as immediately and precisely as possible to patient data, to define the links between mutations, protein dysfunction, and disease expression. This core encourages collaboration of basic and clinical investigators, and therefore hastens the application of new knowledge to patient management and treatment evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COXSACKIEVIRUS 3B PERSISTENCE AND REACTIVATION IN VIVO Principal Investigator & Institution: Feuer, Ralph; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-MAR-2001 Summary: Coxsackieviruses have been implicated in a number of different human diseases, including acute and chronic myocarditis, viral-induced insulin-dependent diabetes mellitus (IDDM), pancreatitis, chronic inflammatory myopathy, and chronic fatigue syndrome. The proposed research will examine the mechanisms of persistence in Coxsackievirus B3 (CVB3) infected mice, using a recombinant virus expressing the enhanced green fluorescent protein (eGFP). Our laboratory has established a solid foundation of molecular and immunological techniques and reagents from previous studies of CVB3 persistence and pathogenesis. Preliminary studies with recombinant eGFP-CVB3 indicate that a certain population of Hela RW cells in culture cannot support a productive infection, including quiescent cells (G0) and cells blocked at the G2/M phase of the cell cycle. The following experiments will test the hypothesis that persistence of CVB3 in mice may rely on infection of quiescent cells incapable of supporting viral replication; and that a subsequent change in the cell-cycle status may lead to virus reactivation and further viral/immune mediated pathology (including myocarditis) in the host. SPECIFIC AIMS: 1. To examine the stability of persistent or latent CVB3 RNA. Quiescent cells infected with eGFP-CVB3 and maintained in serum free media without passage will be monitored at multiple time points for viral replication (plaque assay) and for stability of viral RNA (RT-PCR). Virus rescue will be observed (GFP, RT-PCR, and plaque assay) after cell stimulation with 10 % FBS. 2. To investigate what factors or stimuli may be involved in reactivation of CVB3. Transgenic mice expressing SV40 T antigen in cardiac tissues will be characterized for greater pathogenesis following infection with eGFP-CVB3 by histology and GFP fluorescence. Stimulated PBLs from persistently infected mice will be examined for CVB3 reactivation by GFP expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYSTEINE STRING PROTEIN AND ACUTE PANCREATITIS Principal Investigator & Institution: Groblewski, Guy E.; Nutritional Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706

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Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Acute pancreatitis is an inflammatory disease that is triggered by the premature activation of proteolytic zymogens in acinar cells. As a protective mechanism, zymogens are synthesized as inactive pro-enzymes and packaged in specialized secretory granules destined for exocytosis into the pancreatic duct. During pancreatitis, proteolytic zymogens are prematurely activated in acinar cells by aberrantly mixing with hydrolases present in lysosomes. The mixing of lysosomal hydrolases with zymogens occurs in large cytoplasmic vacuoles as a result of pathogenic alterations in acinar cell membrane trafficking. It is well established that the stress-induced expression of heat shock protein-70 (HSP70) in acini provides a natural protective effect against the pathogenic mixing of lysosomal and secretory granule membrane compartments. This proposal is designed to elucidate the mechanism by which HSP70 inhibits the intra-acinar cell activation of zymogens in preventing the onset of acute pancreatitis. HSP70 is a molecular chaperone in the cytosol that requires a co-chaperone protein to stimulate ATPase activation and substrate binding. We have 1) identified an HSP70 co-chaperone protein called cysteine string protein (CSP) in acinar cells, 2) localized this membrane associated molecule throughout the secretory pathway and 3) developed the TAT-fusion protein system to manipulate CSP expression in acinar cells and thereby study its function. We hypothesize that CSP mediates the protective effects of HSP70 against pancreatitis by targeting HSPT0 chaperone activity from the cytosol to the secretory pathway. In Specific Aim 1, mutant forms of CSP that no longer anchor to secretory granule membranes will be overexpressed acinar cells to determine the importance of CSP in targeting HSP70 to these organelles during pancreatitis. In Specific Aim II, short interference RNAs will be used to inhibit CSP expression in pancreatic Iobules and the protective effects of HSP70 on secretagogue-induced acinar cell damage will be evaluated. These studies will allow us to directly evaluate the role of CSP in the secretory pathway of acini under physiological and pathophysiological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINANTS OF PANCREATIC INJURY IN CYSTIC FIBROSIS Principal Investigator & Institution: Accurso, Frank J.; Professor of Pediatrics; Children's Hospital (Denver) 1056 E 19Th Ave Denver, Co 80218 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Marked phenotypic variability in individuals with cystic fibrosis (CF) who have the same CF genotype suggests that modifier genes may play a role in this disorder. Since most abnormalities in CF begin early in life, investigation of determinants of disease in infants and young children may provide insight into pathogenesis. We have observed that circulating immunoreactive trypsinogen (IRT) levels in infants with CF identified through newborn screening are correlated with early pancreatic dysfunction and with pulmonary function at six years of age. IRT is therefore a biochemical marker of early pancreatic disease in CF also carrying implications for early pulmonary disease. In addition, we have observed that IRT is heritable. We therefore hypothesize that early IRT abnormalities in CF are explained in part by genes that modify the CFTR gene effect on pancreatic injury. We will test this hypothesis in infants and young children with cystic fibrosis diagnosed through newborn screening. IRT will be modeled with age using longitudinal mixed effects approaches with a log transformation to produce a quantitative phenotype that will be used in a Transmission Disequilibrium Test (TDT) to determine if IRT is cosegregating with each of the candidate modifiers. Specific modifiers to be tested can

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be categorized as follows: a. Genetic markers lying within the D19S112 region on chromosome 19 that have been linked to intestinal disease in CF, b. Genes coding for pancreatic enzymes that are capable of causing local tissue injury, c. Genes coding for pancreatic proteins capable of modulating local tissue injury, d. Genes coding for pancreatic membrane transporters, and e.Putative modifier genes of other CF organ involvement. Candidate genes with common, known functional variants will be studied through genotyping. Genes with no known functional variants will be sequenced in a subset of patients exhibiting either "rapid" or "slow" decline in IRT to identify potentially useful mutations or polymorphisms. Sequences of interest will then be examined in the entire study population, with priority as follows: obvious mutations (for example nonsense, frameshift and splice type), then promoter or missense alleles, then variants non- randomly segregating among the IRT "rapid" or "slow" decliners, and then more common variants. We also plan to establish a clinical database and a DNA repository for infants identified by newborn screening. Achieving our goals will likely provide: 1. Insight into the mechanisms of early pancreatic injury, 2. Clues to the pathophysiology of other organs involved in CF, 3. Valuable prognostic information for counseling families of newly diagnosed infants, 4. Information useful for future investigation of the pancreatic complications of CF in later life including recurrent pancreatitis and cystic fibrosis related diabetes. Our long-term objectives are to find new approaches to the early treatment of CF in order to delay pancreatic injury and the development of lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINATION OF CFTR GENE MUTATIONS IN RECURRENT & CHRONIC PANCREATI Principal Investigator & Institution: Freedman, Steven D.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIET, DISEASE, AND PANCREATIC ENZYME SYNTHESIS IN HUMANS Principal Investigator & Institution: O'keefe, Stephen J.; Internal Medicine; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: Acute pancreatitis is a disease of high mortality, induced by premature activation of digestive enzymes in the pancreas, and accompanied by a severe systemic immunoinflammatory response and protein catabolism. Meeting nutritional needs is difficult because food-induced pancreatic stimulation may exacerbate the disease process, and intravenous nutrition (TPN), while "resting the pancreas," increases the risk of septicemia and mucosal atrophy. Recent controlled clinical trials suggest that tubefeeding with elemental diets has advantages over TPN with regard to cost, safety (less infective complications), and efficacy (more anticatabolic). However, it is unknown in humans whether elemental diets stimulate the pancreas, and the beneficial effects may simply reflect better metabolic control and fewer serious complications. Consequently, Dr. O'Keefe and colleagues plan to measure the effects of duodenal infusions of elemental diets on pancreatic enzyme synthesis and secretion in normal volunteers and patients with acute pancreatitis using a unique method that they have developed, based

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on the 6-hr intravenous and enteral infusion of two isotope-labeled amino acids and measurement of their uptake into trypsin and amylase proteins extracted from duodenal secretions. The method also allows them to obtain simultaneous measurements of the rates of protein catabolism and utilization of dietary amino acids for the synthesis of mucosal proteins (obtained by endoscopic biopsy). Studies will be conducted in groups of 8 normal volunteers to compare the relative effects of complex and elemental diets given as duodenal infusions, versus TPN, on the normal response to a complex oral diet. The results will then be used to evaluate the responses in 20 patients with acute pancreatitis randomized to receive enteral elemental or TPN. The results of these investigations are expected to provide valuable new information on both the stimulatory effects of food on the human digestive system and the nutritional value of modern nutritional support techniques, and help determine why elemental diets are more effective than TPN in the management of patients with acute pancreatitis. The results are also expected to form a scientific basis for the design of disease-specific diets for patients with acute pancreatic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISEASE VARIABILITY IN PATIENTS WITH CFTR GENE MUTATIONS Principal Investigator & Institution: Durie, Peter; Professor; Hospital for Sick Chldrn (Toronto) 555 University Ave Toronto, Timing: Fiscal Year 2001 Summary: The range and severity of CF disease is extremely heterogeneous. Our evaluation of a large number of well defined patients with "typical" and "atypical" CF disease and those suspected of having CF are elucidating the relative influence on the disease phenotype of genetic factors including the different CFTR gene mutations and other modulatory genetic factors. Our overall goal is to establish a comprehensive understanding of the spectrum of CF disease associated with mutations and/or variants in the CFTR gene. As well, some variability in CF disease expression between patients with the same genotype (and in specific organs) will be due to the effects of "Modifier" genetic variants on a patient's genome. The specific aims of this application are to:. define CF phenotypes by identifying CFTR gene mutations in well defined patient cohorts with: a conventional diagnosis of CF, "atypical" CF and those suspected of having CF. define the natural history of CF disease in patients with CFTR gene mutations who are diagnosed by conventional diagnostic criteria or have "atypical" CF phenotype including males with infertility and patients with idiopathic pancreatitis. determine the frequency of CFTR gene mutations in cohorts with disease phenotypes resembling CF including asthma, chronic lung disease, and neonates with high immunoreactive trypsinogen and normal sweat test. evaluate obligate heterozygotes with different CFTR gene mutations for evidence of CF phenotypes. determine, in the above mentioned patient cohorts, the relative influence in the CF phenotype the different CFTR gene mutations and modifier genes. Taken together, we will help to clarify the diagnosis of CF disease and ultimately, our findings will lea to significant advances in diagnosis and therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOTOXIN ASSAY FOR ANALYSIS OF SEPTICEMIA DAMAGE Principal Investigator & Institution: Segal, Gershon; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218

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Timing: Fiscal Year 2001 Summary: In the United States, septicemia is the 13th leading cause of death, and accounts for $5 - 10 billion health care dollars spent annually. Patients at risk of developing sepsis frequently present initially to the Emergency Department (ED), with a 'preseptic' syndrome, known as 'systemic inflammatory response syndrome' (SIRS). Prompt recognition, evaluation and initiation of therapy in this group of patients is an area of intensive investigation, since early therapeutic intervention with well established modalities (intravenous fluids and antibiotics) has been shown to be associated with improved outcomes. Furthermore, advances in understanding of the pathophysiology of bacteremia has opened the door for the development of additional therapeutics (e.g. antiendotoxin antibodies) for interrupting the cascade of events associated with full blown sepsis. Establishing an early diagnosis of septicemia remains challenging however. Not all patients with SIRS (fever, tachycardia, tachypnea, and elevated white blood cell count) have a bacterial infection. SIRS can also occur in patients with severe trauma, pancreatitis, and burns without infections. Additionally, demonstration that an infection is the inciting stimulus for SIRS is complicated by the fact that culture reports are usually not available for 24-48 hours, and blood cultures are positive in only about 60% of cases of sepsis. A sensitive and specific clinical diagnostic test for earlier detection of infection would allow physicians to make the diagnosis of septicemia more rapidly, and identify patients who would benefit from specific therapy. Previous efforts toward the development of an assay for early detection of bacteremia have focused on gram-negative infections, as these bacteria are responsible for the majority of cases of sepsis in the United States. The only test currently available assay, the Limulus amebocte lysate test (LAL) is an indirect semiquantitative assay, which has variable sensitivity and specificity and is thus utilized only for industry and research purposes. Recent investigations from the sponsor of this protocol (LINK technology) have demonstrated that a ligand binding assay (LBA) exceeds the sensitivity and specificity of the LAL for the detection of endotoxin in plasma, and may therefore provide the first clinically useful test for early identification of patients with gram negative septicemia. LINK's endotoxin test is based on the core discovery that endotoxin binds to an A1 adenosine receptor. A sensitive and specific clinical diagnostic that quantitates the level of endotoxin in blood has a broad range of clinical uses including: (a) early diagnosis of gram negative septicemia allowing for antibiotic specific therapy; (b) early prediction of impending organ dysfunction; and (c) monitoring of the effectiveness of antibiotics or other therapeutic agents targeted at eradicating the infection and treating the complications associated with gram negative bacteremia. We hypothesize that the detection of endotoxin in human blood by a LBA is an early, sensitive, and specific predictor of organ dysfunction associated with gram negative septicemia. The following specific objectives for this pilot study are: 1) to establish the relationship between the LBA and organ dysfunction; 2) to estimate the correlation of diagnostic errors between the LBA and blood culture; and 3) to identify potential confounders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENOS IS PROTECTIVE IN THE INITIATION OF PANCREATITIS Principal Investigator & Institution: Dimagno, Matthew J.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Pharmacological inhibition of nitric oxide synthase (NOS) or enhancement of nitric oxide (NO) in experimental acute pancreatitis (AP) has yielded mixed results, in part because three NOS isoforms exist: neuronal- (nNOS),

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endothelial- (eNOS) and inducible- (iNOS). Our preliminary data clarifies the role of NO during the initiation of AP and shows that pharmacologic NOS blockade and eNOS deletion, but not nNOS or iNOS deletion, enhance the initiation of an in vivo caerulein hyperstimulation model of AP. By contrast pharmacologic NOS blockade during in vitro caerulein AP has no effect on conversion of intraacinar trypsinogen to trypsin, a hallmark of AP, suggesting that eNOS-derived NO arises from a non-acinar source and/or acts on a non-acinar target. Our data also suggests that upregulation of endothelial eNOS by Simvastatin and Cytochalasin D may attenuate in vivo caerulein AP. We hypothesize that eNOS-derived NO indirectly inhibits initiation of AP by enhancing pancreatic microvascular perfusion. We plan to confirm whether eNOSderived NO acts on a non-acinar target by using an in vitro caerulein model of AP in isolated eNOS KO acini vs. WT acini. Secondly we plan to assess differences in pancreatic perfusion between eNOS KO mice and WT mice during AP using dyelabeled microspheres. Third we plan to determine whether the enhanced initiation of in vivo AP in eNOS KO mice (compared with WT mice) may be normalized by augmenting pancreatic perfusion with NO donors. Fourth we plan to upregulate eNOS pharmacologically in WT and eNOS KO mice to assess for protection against in vivo caerulein AP. We hope that this study may further clarify the role of NO in the pathogenesis of AP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXOCRINE PANCREATIC ZYMOGEN ACTIVATION Principal Investigator & Institution: Gorelick, Fred S.; Professor of Medicine; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 15-JUL-1998; Project End 31-MAR-2007 Summary: (provided by applicant): The pathologic proteolytic activation of digestive zymogens within pancreatic acinar cells is a key step in the initiation of pancreatitis. The extracellular and intracellular mechanisms responsible for this activation remain unclear. Supraphysiologic concentrations (>10 fold than required for maximal secretion) of the physiologic ligand, cholecystokinin (CCK), given in vivo cause zymogen activation and pancreatitis. Similarly treated isolated acinar cells respond with zymogen activation and are injured. Factors that can sensitize the acinar cell to the pathologic effects of CCK might be relevant to the pathogenesis of acute pancreatitis. Several experimental studies suggest that CCK-activated pathways contribute to disease. These include pancreatitis induced by ischemia, bile salts, the CDE diet, and ethanol. We hypothesize that: 1) clinically relevant agents or conditions can either act alone or sensitize the acinar cell to the effects of CCK on zymogen activation, and 2) such activation will depend on Ca2+-dependent and independent mechanisms. We find that the following relevant factors sensitize the acinar cell to zymogen activation caused by physiologic concentrations of CCK: secretin, VLDL, and short chain fatty acids. With respect to alcohols, sensitization increased with chain length and deceased with branching. At sensitizing concentrations, alcohols caused no detectable changes in either cytosolic Ca2+ signaling or secretion. However, the sensitizing effects of secretin corresponded to effects on CCK induced Ca2+ signaling. Previous studies suggested that a low pH compartment mediated zymogen activation. We find that inhibitors of vacuolar (v) ATPase (bafinomycin and concanomycin) block CCK-induced zymogen activation. Using antibodies to subunits of vATPase, we observed translocation during CCK treatments. Thus, vATPase appears to be activated and contribute to zymogen activation. We plan to examine the cellular signaling pathways stimulated by these sensitizing agents with particular emphasis on Ca2+, cAMP, PKC, and vATPase.

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Further, we will examine the effects of the sensitizing agents on cell injury and the trafficking of active enzymes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FATTY PANCREATITIS

ACID

ETHYL

ESTERS

IN

ETHANOL-INDUCED

Principal Investigator & Institution: Kaphalia, Bhupendra; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Pancreatitis is a major health problem in alcoholics that causes high mortality and morbidity, and after biliary duct diseases, chronic alcohol abuse is the second major cause of chronic pancreatitis. However, the mechanism of alcohol-induced pancreatitis is poorly understood. Oxidative metabolism of ethanol catalyzed by alcohol dehydrogenase (ADH) is negligible in the pancreas, while nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs), catalyzed by FAEE synthase, appears to be the major mechanism of ethanol disposition in the pancreas during chronic alcohol abuse. Surprisingly, very little is known regarding the role of endogenously formed FAEEs in ethanol-induced pancreatitis. Based upon our preliminary studies showing - 14-fold increase in FAEE levels in the pancreas of hepatic ADH-deficient (ADH-) deer mice as compared to those in ADH-normal deer mice, and a dose- and time-dependent formation of FAEEs and FAEE-induced apoptosis upon ethanol exposure of ADH-deficient human hepatocellular carcinoma (HepG2) cells in culture, we hypothesize that increased formation of FAEEs is a triggering event in ethanol-induced pancreatitis, and that FAEEs and FAEE synthase can be early markers of pancreatic injury. Our preliminary studies also indicate that FAEEs are formed in rat pancreatic tumor (AR42J) cells in culture. Therefore, to investigate the toxic potential of endogenously formed FAEEs and elucidate their role in ethanol-induced pancreatic injury, we will use ADH- deer mice and AR42J cells. In Aim 1, we will determine the levels of FAEEs in the plasma and pancreas of ADH- deer mice after ethanol exposure in a dose- and time-dependent manner, and evaluate the biochemical and morphological parameters associated with pancreatic injury. We will evaluate apoptosis in the pancreas of ADH- deer mice, and in AR42J cells, after ethanol exposure (Aim 2). Inhibitors or inducers of FAEE synthase to attenuate or augment formation of FAEEs in AR42J cells, respectively, will be used to further examine the role of endogenously formed FAEEs in ethanol-induced apoptosis and toxicity (Aim 3). Achieving our Specific Aims 1-3 should establish the role of FAEEs in ethanol-induced pancreatic injury, lay the foundation for future human studies to develop these parameters as early markers for ethanol-induced pancreatic damage, and ultimately benefit us in developing new preventive/therapeutic strategies for early intervention before irreversible damage to pancreas occurs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GASTROINTESTINAL PROGRAM PROJECT Principal Investigator & Institution: Potter, John D.; Member & Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 18-AUG-1998; Project End 31-MAY-2003 Summary: Research in colorectal and pancreas cancer is proposed. It takes as its theme the following model: the interaction of cells with DNA damaging agents can result in three classes of cells-normal cells with intact DNA; cells with damaged DNA that undergo apoptosis; and cells which, despite DNA damage, fail to suicide. We propose to

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explore aspects of the differences in these three classes of cells to increase our understanding of the carcinogenesis process, to monitor interventions, identify markers that may be used for population screening, and to exploit for therapeutic purposes. Project 1 focuses on oxidative damage and apoptosis among a high-risk human populations- with pancreatitis- and an animal model in order to establish the roles of oxidative DNA damage and antioxidants in pancreatitis and pancreas cancer, and to develop a clinical screening test. Project 2 also focuses on a high-risk inflammatory disease- ulcerative colitis-in order to determine the role of DNA damage and mutagenesis in the progression of UC dysplasia. In addition, an intervention with antioxidants is proposed to reverse of slow the dysplasia neoplasia sequence. Project 3 focuses on colonoscopy patients with the specific aim of identifying several processes in the pathways to neoplasia, including oxidative damage and changes in expression of apoptosis-related proteins, that will allow the early identification of high-risk individuals in a low-cost, minimally invasive manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC CONTRIBUTION TO THE STRESS RESPONSE Principal Investigator & Institution: De Maio, Antonio; Associate Professor; Surgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: (Adapted from the applicant's abstract): The sequential collapse of different organ systems days or weeks after severe trauma, sepsis, pancreatitis, and shock, termed multiple organ dysfunction syndrome (MODS), is the most important cause of mortality and morbidity of patients admitted to the surgical intensive care unit. Recent studies have suggested that MODS is caused by an overwhelming inflammatory response as part of the host defense system. One important clinical observation is the heterogeneous response observed in patients after similar stresses. A possible explanation for this observation is that the response to stress is influenced by the patient's genetic background. Thus, the central focus of this proposal is to evaluate whether genetic diversity may contribute to the inflammatory response after stress. Inbred mouse strains will be used to test this hypothesis. This information will provide us with a better understanding of the inflammatory process and the indentification of genes that modulate the inflammatory response. This is a novel approach to a problem whose solution has been elusive using conventional methodologies. The specific aims of the project are: 1) To compare the inflammatory response between C57Bl6/J and A/J mice. The hypothesis to be tested is that the genetically distinct mouse strains, C57Bl6/J (B6) and A/J have significant differences in their inflammatory response. A comparison of the inflammatory response between these two mouse strains will be performed after two different, but related, stresses: administration of E. coli LPS, and peritonitis induced by cecal ligation and puncture (CLP). This study is also pertinent to the development of quantitative assays for the screening of recombinant inbred (RI) mouse strains (Specific Aim 2), and the identification of possible candidate genes for a positional cloning effort (Specific Aim 3). 2) To map loci responsible for strain-specific differences in the inflammatory response. The phenotypes modulating the inflammatory response of B6 (sensitive) and A/J (resistant) mice will be characterized after administration of LPS or following CLP. The assays to be used are: the infiltration of leukocytes in liver and lung, and assessment of plasma cytokine levels (TNFa and IL-B). Loci governing these responses will be mapped using RI strains (AxB and BxA). 3) Identification of candidate genes contributing to differences in the inflammatory response. The positions of those loci with the strongest contribution to the phenotypes described in Specific Aim 2 will

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be refined with backcross and intercross strategies (high resolution mapping) and subjected to a positional cloning effort. The results from this analysis will provide us with candidate genes that contribute to the heterogeneity of the inflammatory response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEAT SHOCK PROTEINS AND PANCREATITIS Principal Investigator & Institution: Saluja, Ashok K.; Professor of Surgery and Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): The broad, long-term aim of the work proposed in the present application is to determine the role of prior stress and heat shock proteins in regulating the severity of pancreatitis-a disease with considerable morbidity and mortality. The pathophysiological alterations underlying the development and ultimate severity of pancreatitis are not fully understood, but it is generally believed that premature activation of digestive enzyme zymogens within the pancreatic acinar cells themselves leads to acinar cell injury and pancreatitis. The mechanisms involved in this activation process are still controversial. Recent observations suggest that prior stress by either water immersion or hyperthermia ameliorates subsequent development of pancreatitis in rats. This proposal is based on our hypothesis that prior stress prevents pancreatitis by specifically increasing the expression of heat shock proteins (HSPs). Once upregulated, HSPs prevent premature activation of trypsinogen by blocking its colocalization with lysosomal enzymes. Furthermore, we believe that HSPs affect these phenomena by attenuating the sustained rise in intracellular Ca2+ which is normally observed during pancreatitis. The proposed studies will pursue the following specific aims: (a) to determine whether HSPs are actually responsible for post-stress protection against pancreatitis and whether that protection is generalizable to models of pancreatitis other than the caerulein-induced model; (b) to elucidate the mechanism of stress-induced protection against pancreatitis, and (c) to determine the mechanism by which HSPs alter intracellular Ca2+ homeostasis. These studies will use two different models of pancreatitis: (a) caerulein model in mice and rats and (b) bile salt-induced pancreatitis in rats. Stress and HSP expression will be induced by both physical and chemical approaches. Successful completion of these studies will eventually help us in planning strategies to pharmacologically manipulate the levels of HSPs, so that their induction can be used as a tool to decrease the severity of clinical pancreatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HYPOXIA AND FREE RADICALS IN ALCOHOLIC PANCREATITIS Principal Investigator & Institution: Arteel, Gavin E.; Pharmacology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 30-JUN-2002 Summary: APPLICANT'S ABSTRACT: We hypothesize that ethanol-induced chronic pancreatitis is triggered by hypoxia/reoxygenation injury, leading to stimulation of inflammatory cell recruitment and activation of these cells by circulating endotoxins. We recently showed pancreatic injury characteristic of chronic pancreatitis in humans in an enteral model modified to deliver higher amounts of ethanol. Our first goal is to characterize this new model. Wistar rats will receive alcohol internally using our modified protocol for up to 6 months. Pancreatic function and injury will be determined and compared to changes in key molecular events. We expect that alcohol will cause

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progressive, irreversible changes in pancreatic morphology and function, similar to clinical observations. We will next test the hypothesis that alcohol causes hypoxia in pancreas in vivo. Initially, we will determine if the hypoxia marker pimonidazole can be used to index pancreatic hypoxia in rats. We will then determine the effect of alcohol on pancreatic hypoxia in our enteral model. We expect that chronic ethanol will cause early increases in hypoxia, suggesting that hypoxia might play a key early role in the initiation of damage. The effect of removing endotoxin by lactobacillus treatment to displace Gram-negative bacteria, or killing macrophages with silica will next be studied. We expect pancreatic damage will be blunted by these treatments, suggesting a role of endotoxin and macrophages in chronic alcoholic pancreatitis. Next, the hypothesis that free radicals play a causative role in chronic alcoholic pancreatitis will be tested. This question will be addressed using adeno-associated virus (RAAV) to deliver superoxide dismutase (SOD) and cause stable long-term pancreatic expression. First, optimal conditions to confer pancreatic transgene expression will be determined. The effect of RAAV containing superoxide dismutase (SOD) on pancreatic injury will be determined. Free radical formation and oxidative stress will also be quantitated. We expect that preventing oxidative stress with SOD will protect against chronic alcoholic pancreatitis, indicating that free radicals play an important role in the progression of chronic alcoholic pancreatitis. This work will lay the mechanistic foundation for future studies of targeted therapies to prevent alcoholic pancreatitis that can applied in the clinic, where such therapy is desperately needed. Further, through didactic training and interactions with his mentor and key faculty in the enteral model of alcohol exposure, molecular biology, and viral vector gene therapy, the applicant will acquire new skills that will greatly enhance his career development and bridge the gap to becoming a successful member of the academic and scientific community. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN AUTOIMMUNITY

VIVO

ROLE

OF

CTLA-4

IN

COSTIMULATION

AND

Principal Investigator & Institution: Sharpe, Arlene H.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2002 Summary: (Adapted from the Investigator's abstract): The investigator will test the hypothesis that CTLA-4 downregulates T-cell activation and is normally involved in the prevention of autoimmunity. Evidence for this premise comes from the investigator's finding that the CTLA-4-deficient mice develop splenomegaly and lymphadenopathy, multi-organ lymphocytic infiltration and tissue destruction with severe myocarditis and pancreatitis, and die by 3-4 weeks of age. Three specific aims will be tested. The role of CTLA-4 in regulation of T-cell dependent immune responses will be analyzed by determining how CTLA-4 deficiency affects T-cell responses in vitro and whether CTLA-4 mediates its inhibitory effects solely through interactions with B7-1 and B7-2. The mechanisms of CTLA-4-mediated inhibition will be studied using naive and activated T-cells from CTLA-4-deficient, TCR transgenic mice. Emphasis will be placed on susceptibility to apoptosis and lymphokine production. The contribution of CTLA-4 to systemic autoimmune responses will be addressed by assessment of the pathology of in CTLA-4-deficient mice, determination of whether self-reactive T-cells appear in CTLA-4-deficient mice, and whether the course of EAE in MBP-specific TCR transgenic mice is altered when these mice lack CTLA-4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LANTHANIDES AS NOVEL ANTI-ARTHRITIC AGENTS Principal Investigator & Institution: Evans, Christopher H.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The lanthanides, also known as the rare earths, comprise a series of 15 elements spanning atomic numbers 57-71. Lanthanide ions (Ln3+) are of approximately the same ionic radius as Ca2+ ions, and share many other chemical properties, including ligand preference and geometry. They frequently replace Ca2+ in an isomorphous fashion on biological macromolecules, organelles and cells. Because of their greater charge: volume ratio, binding constants are higher for than Ca2+, and they often interfere with Ca-dependent biological functions. One example of importance to this proposal, is the ability of to suppress macrophage activation in vivo. have been shown to reduce mortality in rats challenged by anaphylaxis, endotoxin, pancreatitis and other macrophage-dependent pathologies. Funding is requested to determine whether also inhibit the development of experimental models of RA in rats. Two such models will be evaluated: antigen-induced arthritis, using ovalbumin as the inciting antigen, and adjuvant arthritis. These two models are selected because has been shown to inhibit anaphylactic responses to ovalbumin in sensitized animals, and also to suppress inflammatory responses to Freund's complete adjuvant, the inciting agent in adjuvant arthritis in rats. Three different members of the lanthanide series will be tested: lanthanum (Ln3+), the largest member of the series, gadolinium (Gd3+), which lies in the middle of the series and has been widely used as a therapeutic agent in rats, and lutetium (Ln3+), the smallest lanthanide. will be evaluated both as free cations and as complexes with citrate to improve their solubility and mobility. Lanthanides will be injected systemically and intra-articularly. A successful outcome to these studies will have identified the basis for a potential new, very inexpensive anti-rheumatic agent whose mode of action differs from that of existing drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LEXIPAFANT IN HIV DEMENTIA--TOLERABILITY AND SAFETY, PLACEBO CONTROLLED Principal Investigator & Institution: Mcarthur, Justin C.; Professor of Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: Antiretroviral agents are currently the only approved therapy for treatment of HIV dementia, but treatment response is frequently unsatisfactory or short-lived, or agents poorly tolerated in doses adequate for CNS penetration. The reason for the incomplete response may be that the pathophysiology of HIV-related cognitive impairment is initiated by the virus, but involves a complicated inflammatory cascade within the brain. Therefore, effective therapy needs to focus on these indirect mechanisms in addition to viral suppression. One hypothesis for the pathophysiology of dementia is that neurotoxic substances are produced by specific interactions between infected macrophages and astrocytes to damage and destroy neurons. In this schema, we are interested in the role of the lipid inflammatory mediator, platelet activating factor (PAF). This is a potent biological mediator that exerts its effects in as variety of cells and tissues and has been detected at high levels in the CSF of immune-suppressed HIV-1 infected patients with CNS dysfunction. Lexipafant is a PAF antagonist with high affinity for the PAF receptor with an excellent safety profile. Currently, controlled clinical trials of Lexipafant are under way in treatment of asthma, pancreatitis,

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ulcerative colitis and pre-operative ischemia. It has shown to be active via oral route and is well- tolerated in human volunteers using doses up to 750 mg bid. No prior clinical research has been reported with Lexipafant in HIV-infected individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVER-LUNG INTERACTION DURING ACUTE PANCREATITIS Principal Investigator & Institution: Gray, Keith D.; Surgery; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 05-FEB-2002 Summary: A prominent feature of severe acute systemic inflammatory response syndrome (SIRS) including acute respiratory distress syndrome (ARDS). The physiology of these responses appears remarkably similar to responses to direct liver injury in other settings. Cytokines produced in the liver and lungs, including tumor necrosis factoralpha (TNF-alpha) and interleukin (IL-1), are implicated in the pathogenesis of SIRS and animal experiments have demonstrated them capable of precipitating acute lung injury. During acute pancreatitis, proteases are released into the portal system, exposing the liver to high levels of activated enzymes. Nuclear factor kappa-B (NF-kappaB), a transcriptional regulator of TNF- alpha, IL-1 and other cytokines, is activated in the pancreas within 30 minutes of inducing experimental acute pancreatitis and subsequently within the liver and lung within 24 hours of acute liver injury. Our central hypothesis is that NF-kappaB activation in the pancreas and liver mediates acute lung injury associated with pancreatitis. Using the biliary cerulein/glycodeoxycholic acid model of acute pancreatitis will address two specific aims: 1) to determine whether altering NF-kappaB activation in the liver affects the pulmonary response to severe acute pancreatitis; 2) to determine the role of Kupffer cells in mediating the multisystem effects of pancreatitis by depleting Kupffer cells prior to induction of pancreatitis. These studies may allow the development of strategies to ameliorate multisystem to ameliorate multi-system injury including pulmonary failure, which can be devastating during this illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MAT1A NULL MOUSE: MODEL FOR ALCOHOLIC TISSUE INJURY Principal Investigator & Institution: Lu, Shelly Chi-Loo.; Professor of Medicine; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): Methionine adenosyltransferase (MAT) is a critical enzyme responsible for the biosynthesis of S-adenosylmethionine (SAM). Of the two genes (MAT1A, MAT2A) that encode MAT, MAT1A is mainly expressed in adult liver. Due to differences in kinetics and regulatory properties, cells expressing MAT1A have much higher SAM levels than cells expressing MAT2A. Cirrhotic patients have decreased hepatic MAT activity and SAM biosynthesis. SAM has been used therapeutically but the molecular targets remain unclear. Recently we showed the importance of MAT1A in maintaining a normal liver phenotype using the MAT1A null mice. Three-month old MAT1A null mice have reduced hepatic SAM and GSH levels, hyperplasia, spontaneous oxidative stress, increased cytochrome P4502E1 (CYP2E1) expression and are prone to liver injury. On a normal diet, MAT1A null mice develop non-alcoholic steatohepatitis by 8 months and hepatocellular carcinoma by 18 months. Further, we discovered that the once thought to be liver-specific MAT1A is highly

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expressed in normal pancreas and pancreatic acini. MAT expression undergoes dramatic changes and pancreatic SAM level fall in female mice fed a choline-deficient ethionine supplemented diet (a model of necrotizing pancreatitis). SAM supplementation prevented pancreatic injury in this model and ameliorated injury due to cerulein infusion, a more acute model of pancreatitis. Although pancreatic injury is normally absent in rodents fed ethanol, they are more susceptible to cerulein-induced injury. Pancreatic SAM levels fell during ethanol feeding and may sensitize the organ to further injury. Given these provocative results, we hypothesize that MAT1A null and heterozygous mice are more susceptible to ethanol-induced tissue injury and may serve as a novel model to study the pathogenesis and treatment of these diseases. The aims of the proposal are: 1) examine the effect of SAM depletion and treatment in ethanolinduced liver injury-examine whether SAM depletion predisposes to ethanol-induced injury and whether SAM is effective therapeutically in the absence of MAT1A; 2) examine the effect of SAM depletion and treatment in ethanol-induced pancreatic injury-examine whether SAM depletion predisposes to ethanol-induced pancreatic injury and the effect of SAM treatment; 3) elucidate the mechanisms of SAM depiction's sensitizing effect on liver injury-examine the role of CYP2E1, mitochondrial GSH and hepatic macrophage activation in SAM depletion s sensitizing effect; 4) identify the molecular targets of SAM's therapeutic effect in alcoholic liver injury-identify targets of SAM using genomics and proteomics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEDICAL HISTORY, MEDICATIONS, AND PANCREATIC CANCER RISK Principal Investigator & Institution: Mandelson, Margaret T.; Associate Investigator; Center for Health Studies Seattle, Wa 98101 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Risk factors for pancreatic cancer are not well established. The goal of this pilot study is to investigate the relation between medical history, medication use and pancreatic cancer in a case-control study based on medical record abstraction and electronic laboratory and pharmacy data. Our specific aims are: 1. To investigate the relation between medical conditions and pancreatic cancer risk, focusing on: a. Diabetes mellitus, including disease duration, therapy, and glycemic control. b. Pancreatic inflammation, including acute and chronic pancreatitis. c. History of peptic ulcer disease and/or infection with Helicobacter pylori (H. pylori). d. History of cholecystectomy and/or cholelithiasis. 2. To investigate the relation between the use of medications and pancreatic cancer, focusing on nonsteroidal anti-inflammatory drugs, cholesterol lowering agents including HMG-CoA reductase inhibitors and acid suppressive medications including histamine receptor antagonists and proton pump inhibitors. As a secondary specific aim we propose to examine additional medical conditions and medications in order to generate hypotheses for future studies of the epidemiology and prevention of pancreatic cancer. These include evaluation of medical conditions such as irritable bowel syndrome, allergies and asthma as well as medications including immunosuppressive medications and angiotensin converting enzyme inhibitors. To meet these specific aims we propose to conduct a case-control study of pancreatic cancer comprised of 250 newly diagnosed cases and 1,000 controls in the defined population of Group Health Cooperative, a large health maintenance organization. Data on prior medical conditions and medications will be collected through abstraction of traditional and computerized medical records, including electronic laboratory and pharmacy data. Study strengths include the availability of

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uniformly collected, long-term medical and pharmacy data and the availability of data on important covariates, including smoking. The proposed study will provide a unique opportunity to investigate the role of medical conditions and medications in pancreatic tumorigenesis and to generate new insights into the mechanisms that result in pancreatic cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODELS OF TYPE 1 AND TYPE II HEREDITARY PANCREATITIS Principal Investigator & Institution: Ulrich, Charles D.; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-MAR-2003 Summary: (Applicant's Abstract): Acute and chronic pancreatitis remain major healthcare problems. The lack of effective preventive and therapeutic strategies in these disease states stems from a lack of understanding regarding disease pathogenesis. The investigator's group has identified mutations responsible for two delayed-onset, autosomal dominant inherited forms of acute and chronic pancreatitis. An RI 17H mutation in the human cationic trypsinogen gene links with type I hereditary pancreatitis (HP I). An N211 mutation in the same gene links with type II hereditary pancreatitis (HP II). Biochemical data from other groups when combined with the results of there preliminary studies support the hypothesis that the HP I mutation in cationic trypsin renders the molecule resistant to proteolytic digestion, the persistence of mutant trypsin activity resulting in the creation of a "milieu" sufficient for clinicallyapparent acute pancreatitis. The alterations in protein biochemistry responsible for the HP II phenotype remain unclear. In an initial attempt to develop an animal model of HP I, the investigator generated transgenic mice containing a diet-inducible pancreatic acinar cell-specific promoter coupled to either wild-type or HP I mutant human cationic trypsinogen. Unfortunately, these mice fail to develop pancreatitis spontaneously, and all available antibodies to human cationic trypsin cross-react with an identically sized mouse trypsin. The investigator believes that enhanced expression of antibody epitopetagged human cationic trypsinogens will provide him with the best opportunity to develop a successful animal model of hereditary pancreatitis. Toward this end, the investigator proposes (1) studies comparing the biochemical properties of affinitypurified recombinant wild-type, R117H, and N21I human cationic trypsinogen/trypsin (+ I- epitope tag) utilizing a validated in vitro assay system. By design, these studies will also further test the investigator's hypothesis with regard to HP I mutant trypsin, and discern the biochemical alterations induced by the HP II mutation. The investigator will then (2) characterize murine pancreata and acinar cells expressing varying levels of epitope-tagged wild-type, R117H, and N2 11 human cationic trypsinogen/trypsin. The development of these animal models, in combination with the experimental design, should provide him with important insights into the events underlying the delayedonset and pathophysiology of HP I, HP II and non-hereditary forms of acute and chronic pancreatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR GENETICS OF HEREDITARY PANCREATITIS Principal Investigator & Institution: Whitcomb, David C.; Professor of Medicine, Cell Biology & Ph; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 30-NOV-2002

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Summary: Acute and chronic pancreatitis are major health-care problems in the United States causing years of pain and disability. Despite the impact of these diseases, mystery surrounds many of the predisposing causes and early molecular events. Furthermore, the devastating effects of acute pancreatitis and chronic pancreatitis, once established, cannot be reversed. We believe that in the future, advances in the treatment of pancreatic disease rest in the early identification of at-risk individuals as well as in the prevention of limitation of pancreatic injury. Thus, the goal of our program is to determine the molecular mechanisms that predispose to acute and chronic pancreatitis and to identify targets for disrupting pathophysiological processes. We believe that effective preemptive actions will prevent or limit pancreatic injury and thus, result in the reduction of he incidence and severity of acute and chronic pancreatitis. To understand the mechanisms of pancreatitis we will identify previously uncharacterized hereditary pancreatitis families and investigate several striking features of this disease including incomplete penetrance and the mechanisms causing pancreatitis with trypsinogen RR117H and N21I mutations. Answering this question may provide insight into the pathophysiology of acute and chronic pancreatitis and identify targets for new therapies, and help identify individuals at risk through genetic testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF PANCREATITIS Principal Investigator & Institution: Logsdon, Craig D.; Professor; Physiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 10-MAY-1998; Project End 31-AUG-2002 Summary: Preliminary data supports an association between activation of stressactivated protein kinase pathway, expression of chemokines, and secretagogue-induced experimental pancreatitis. This work is designed to explore mechanisms and interrelationships between events in these pathways and their role in pancreatitis. The first aim is designed to test the hypothesis that chemokines are specifically and rapidly induced in acinar cells by treatments that induce pancreatitis utilizing the secretagogue hyperstimulation model, intraductal injection of bile salt and protease solutions, and ischemia/reperfusion models of pancreatitis. The second aim explores the hypothesis that activation of the stress kinase pathway is necessary and sufficient for the stimulation of chemokine gene expression. This will utilize both the in vivo animal models of pancreatitis, as well as in vitro studies with dispersed pancreatic acinar cells. The latter allows various manipulations for activation and inhibition of stress kinase signalling cascades, as well as the adenoviral-mediated gene delivery of constitutivelyactive or dominant-negative signalling genes. The third aim tests the hypotheses that NFkB is involved in chemokine gene expression in pancreatic acinar cells. This again utilizes both in vivo and in vitro approaches with various manipulations of NFkB and IkB. The final aim tests the hypothesis that modification of chemokine expression in vivo will influence the severity of pancreatitis. This will attempt to utilize adenoviral vectors to directly express the specific chemokines in the pancreas in vivo and explore effects on the characteristics of pancreatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR PATHOGENESIS OF DIGESTIVE DISEASES Principal Investigator & Institution: Omary, M Bishr.; Professor of Medicine; Medicine; Stanford University Stanford, Ca 94305

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Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 28-FEB-2006 Summary: OVERALL (Adapted from the application) The Digestive Disease Center at Stanford University was established in 1987 and has two major areas of focus. The first deals with studying host-pathogen interactions, and the mechanism and signals that target leukocytes to specific digestive organs and pathogens. Infections under study include hepatitis A-D, H. pylori, and the diarrheal agents rotavirus, salmonella, E-coli, cholera and astrovirus. It also addresses mucosal immunity and targeting of immunocytes to the intestine and liver in normal and disease states including inflammatory bowel disease, viral hepatitis, and H. pylori-induced gastritis. The second focus addresses the cell and molecular biology of digestive epithelia with emphasis on normal and abnormal cell growth, differentiation, development, polarity, and the nature and role of signaling pathways and the cytoskeleton in facilitating these processes. This focus targets several digestive diseases including esophageal, pancreatic and colorectal cancer; cryptogenic liver disease; pancreatitis and Barrett?s esophagus. The Center consists of 29 established investigators who blend several clinical and basic science departments. Five core facilities are administered by the Center and they provide several important technologies and services. The Administrative Core offers the Pilot and Feasibility Program which provides one year funding ($20,000/year) to junior investigators or those with a collaborative project, the Named Investigator Program which provides a two year 20-25% effort/year support to a promising junior faculty, and a Collaborative Trainee Program that specifically funds trainees who work with two or more Center investigators. The Fluorescence Activated Cell Sorting/Immunoprobe Core offers an array of services that allow studying single cells. The Cell Imaging Core offers state of the art imaging tools including confocal and electron microscopy. The Microarray/DNA Sequencing Core offers the ability to identify disease-associated regulatory changes in multiple genes, and as such provides potential means to develop diagnostic and therapeutic modalities. Cell Biology & Signaling Core offers expertise and services in cell culture methods, characterizing protein-protein interaction, dissecting signaling pathway and characterizing regulatory modifications such as phosphorylation. In the aggregate, this Center brings together an accomplished group of investigators, creates a highly interactive environment, and makes available state of the art technologies to address important digestive diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PANCREATITIS

MOLECULAR

PATHOMECHANISM

OF

HEREDITARY

Principal Investigator & Institution: Sahin-Toth, Miklos; Associate Professor; Physiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2004 Summary: (Applicant's abstract): The broad, long-term objectives of this application are to understand the mechanism by which mutations in the human cationic trypsinogen gene (PRSS1) lead to hereditary pancreatitis (HP). HP is an autosomal dominant genetic disorder characterized by early-onset recurrent attacks of acute pancreatitis with frequent progression to chronic pancreatitis and occasionally to pancreatic cancer. HP belongs to the inherited forms of idiopathic chronic pancreatitis, a genetically heterogeneous disease group, where mutations have been found not only in PRSS1, but also in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and in the pancreatic secretory trypsin inhibitor gene (SPINK1). HP has been widely recognized as a highly relevant model system for all forms of human pancreatitis. In the majority of

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cases, three mutations, Arg117-His, Asn2l-,lle, and Ala8-Val, have been identified in PRSSI. The molecular defects caused by the HP mutations will be studied within the context of a current pathogenesis model, which suggests that HP is caused by excessive intrapancreatic trypsin activity via one of 3 mechanisms: (i) increased trypsinogen activation, (ii) decreased trypsin degradation; or (iii) impaired inhibition by pancreatic secretory trypsin inhibitor (PSTI). The principal objective of the experimental design is to study the effects of the HP-mutations in vitro, using recombinant human trypsinogens. Wild-type and mutant trypsinogens will be expressed in Escherichia coli, and purified to homogeneity with ecotin affinity chromatography. Catalytic properties and autocatalytic degradation (autolysis) of trypsins and autoactivation and autocatalytic degradation (zymogenolysis) of trypsinogens will be characterized. In addition, interactions between wild-type and mutant forms of cationic trypsin(ogen) with anionic trypsin(ogen) and mesotrypsin(ogen) will be examined. Finally, inhibition of human trypsin isoforms and HP mutant trypsins by wild-type and mutant PSTI proteins will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NADPH PANCREATITIS

OXIDASE

INHIBITOR

THERAPY

IN

ACUTE

Principal Investigator & Institution: Weinstein, David; Triage Pharmaceuticals, Llc 1 University Pl, Rm A215 Rensselaer, Ny 12144 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2003 Summary: (provided by applicant): Triage Pharmaceuticals LLC ("Triage") was chartered in the summer of 1999 to exploit new treatments for vascular leakage related illnesses using NADPH oxidase inhibitors patented by Dr. James Holland, a Triage cofounder. The invention is protected by two issued U.S. patents, granted European and Japanese patents, and a pending Canadian patent application. These cases claim a method of prevention and treatment of diseases related to endothelial hyperpermeability and vascular leakage by therapeutic administration of an NADPH oxidase inhibitor. The scientific rationale for the involvement of NADPH oxidase in mechanisms leading to vascular leakage has been well-documented by Triage in its work on the inhibitory effect of apocynin, a naturally occurring plant extract. In order to further this work, Triage is seeking funding to perform accelerated pharmaceutical development and preclinical testing for drug candidates in a vascular leakage disease indication that has a clear, simple, non-costly end-point and treatment duration that should allow determination of clinical efficacy in very short trial periods. Using its current library of potent NADPH oxidase inhibitors, "proof of concept" will be established in the vascular leakage of acute pancreatitis using an established rat model of the disease. PROPOSED COMMERCIAL APPLICATION: There are no currently available drugs for the treatment of the endothelial hyper-permeability and vascular leakage component of vascular diseases, such as acute pancreatitis, diabetes mellitus, atherosclerosis and hypertension. Despite the effectiveness of currently available medical treatments for these vascular diseases, the risks of morbidity and mortality remain high. A combination approach with currently available medical treatment and an orally administered NADPH oxidase inhibitor would significantly improve the treatment of individuals with a high risk for the diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURAL REGULATION OF PANCREATIC FUNCTION Principal Investigator & Institution: Kirkwood, Kimberly S.; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 15-MAY-1994; Project End 31-JUL-2003 Summary: (Adapted from Applicant's Abstract): Approximately 10% of patients with acute pancreatitis die from uncontrolled pancreatic inflammation that results in massive fluid losses and shock. The regulation of pancreatic inflammation is poorly understood. In the trachea, sensory nerves regulate inflammation by releasing tachykinins that bind to endothelial cells and induce arteriolar vasodilatation, plasma extravasation and neutrophil infiltration. This well-characterized phenomenon is called neurogenic inflammation. The general hypothesis of this proposal is that neurogenic mechanisms are essential to the pathogenesis of acute pancreatitis. Specifically, we hypothesize that a) tachykinins induce plasma extravasation and neutrophil infiltration in the pancreas by interacting with neurokinin receptors, b) the pro-inflammatory effects of tachykinins are terminated by cell surface peptidases, and c) tachykinins and their receptors regulate inflammation in a widely-used model of acute pancreatitis. Due to the recent availability of "knockout" mice in which the genes encoding neurokinin receptors or cell surface peptidases have been deleted by homologous recombination, these experiments will be performed in mice. Pancreatic inflammation will be assessed by 1) quantifying and localizing plasma extravasation using Evans blue and Monastral blue, respectively, 2) identifying and measuring endothelial cell gaps through which plasma extravasates using a silver stain and light microscopy, 3) quantifying and localizing neutrophil infiltration using myeloperoxidase, and 4) defining the extent of edema, and cytoplasmic vacuolization using histological criteria. Specific Aim 1 will define the contribution of exogenous and endogenous tachykinins to the initiation of acute pancreatic inflammation. The time-course and dose-response will be determined, and the neurokinin receptors that mediate these effects will be identified using antagonists and knockout mice, and localized using receptor-specific antisera. Specific Aim 2 will examine the role of peptidases in the termination of tachykinin-induced pancreatic inflammation. The peptidases neutral endopeptidase and angiotensin converting enzyme will be localized in the pancreas using specific antisera, and their importance in tachykinin-induced inflammation will be determined using inhibitors and knockout mice. Specific Aim 3 will define the importance of sensory nerves, and specifically tachykinins, in the pathogenesis of acute pancreatitis. Using neurokinin receptor antagonists, peptidase inhibitors, and knockout mice, we will delineate the neurogenic mechanisms that regulate inflammation in acute pancreatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROENDOCRINE REGULATION--PANCREATIC HORMONE SECRETION Principal Investigator & Institution: Greeley, George H.; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 16-SEP-1985; Project End 31-MAR-2006 Summary: Our principal hypothesis is that secretion of the intestinal hormone, Cholecystokinin (CCK), as mediated by luminal CK-releasing factor (LCRF). Emerging evidence how indicates that mechanisms underlying stimulation of intestinal peptide hormone secretion involve luminal endocrine-like releasing factors. The long sought after luminal releasing factor for cholecystokinin (CCK) or Luminal Cholecystokinin Releasing Factor (LCRF) has recently been isolated. Our laboratory has shown that

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LCRF is expected primarily in the intestinal epithelium Brunner's glands and pancreatic ductules. We have measured secretion of LCRF into the intestinal lumen by radioimmunoassay. We propose that luminal nutrients provoke LCRF release from the intestinal epithelium. Brunner's glands and pancreatic ductules into the lumen; luminal LCRF than triggers intestinal CK secretion. We also have preliminary data to show the existence of large species of LCRF in the intestinal epithelial and lumen, and that a peptide hormone processing enzyme, pro-hormone convertase- 5 (PC-5) is co-localized and co-secreted with LCRF into the lumen. These findings suggest that LCRF is processed before secretion and post- secretory within the intestinal lumen to a biologically active form by PC- 5. The primary objectives of this research proposal are to characterize the biological activity of LCRF on CCK secretion, and to test the hypothesis that luminal LCRF regulates intestinal CCK secretion. The Specific Aims of this research proposal are; 1) to characterize the biological activity of LCRF on CCK secretion; and, 2) to demonstrate that LCRF mediates physiologically relevant intestinal CK secretion. Accomplishment of our proposed aims will result in fundamental new knowledge regarding the role of LCRF in the regulation of CCK secretion and its potential for therapeutic applications in digestive diseases, including pancreatitis, gallstone diseases, motility and eating disorders. LCRF appears to represent a unique model of endocrine peptide secretion and processing since LCRF may be the first described lumone. Lumones are hormone- like factors produced by intestinal cells, secreted into the intestinal lumen and delivered to their target cells residing in the intestinal epithelium. The intestinal lumen may be an important pathway for endocrine secretion and action and regulation of gastrointestinal function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROGENIC AMPLIFICATION OF PANCREATITIS PAIN Principal Investigator & Institution: Westlund-High, Karin N.; Professor; Marine Biomedical Institute; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Visceral pain is of great concern since it constitutes a large part of the pain treated by the medical community. Pain is a major complaint in particular of patients with pancreatis or pancreatic cancer. The pain can be severe and intractable, resistant even to morphine. Our previous studies have determined that pain in patients with cancer involving the pelvic visceral organs is relieved by a neurosurgical lesion limited to the midline of the dorsal column of the spinal cord. In rats we determined that sensory input from the colon is primarily transmitted to higher brain sensory processing centers as a midline component of the dorsal column pathways. This raises the possibility of a major visceral pain pathway in the dorsal column which we will consider as an overall hypothesis. We propose further study of this previously unrecognized visceral pain pathway relevant to transmission of pancreatic inputs from thoracic levels. Our preliminary data support the following hypothesis for transmission of pancreatic nociceptive information: Nociceptive information from the pancreas is transmitted to cells located medially in the spinal cord. These cells send their axons up the dorsal columns in a previously undescribed pathway between the gracile and cuneate fasciculi to innervate the edges of the dorsal column nuclei in the medulla. The information is then relayed to the thalamus. One aim of the proposed studies will define the central neuronal pathway responsible for transmission of noxious information evoked by electrical and chemical stimulation of pancreatic afferent fibers in rats. The route of the pathway to sensory processing centers will be mapped. One aim will assess pathway

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disruption as a means of abrogating pancreatic nociceptive transmission. Another aim will examine pharmacological intervention with glutamate receptor antagonists in pancreatitis models. This project using a multidisciplinary approach including electrophysiological, behavioral and anatomical methods should provide information fundamental to the understanding of nociceptive processing in these devastatingly painful conditions involving the pancreas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION

NEUROPEPTIDE

REGULATION

OF

ENTEROPANCREATIC

Principal Investigator & Institution: Mulholland, Michael W.; Professor of Surgery; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JAN-1991; Project End 31-DEC-2003 Summary: The intrinsic nervous system of the gastrointestinal tract affects nearly aspect of digestive activity. While dysfunction of the autonomic nervous system has been postulated to cause or exacerbate several pancreatic diseases, little is known of the factors influencing signal processing and function of the enteropancreatic nervous system. As one of example, chronic pancreatitis is a devastating condition characterized by pain and exocrine insufficiency, in which abnormalities of neural function have been postulated to play a role. The current treatment of chronic pancreatitis is impiric, palliative and unsatisfactory, reflecting our lack of basic information. The following research project is designed to investigate on a fundamental level neural control mechanisms that have relevance to human health. We have hypothesized that: 1. Pancreatic nerves activate a functional domain consisting of multiple acini innervated by a single neuron; 2. Pancreatic neurotransmission is acutely regulated by presynaptic modulation of calcium-dependent signaling pathways; 3. For enteropancreatic neurons, long-term function is regulated, at the transcriptional level, by the duration and intensity of signaling activities; 4. In acinar cells, both enzyme secretion and gene expression are regulated via neural mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NON-INVASIVE IMAGING OF INSULITIS IN TYPE 1 DIABETES Principal Investigator & Institution: Denis, Maria C.; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by the applicant): Type 1 diabetes develops through an initial phase, termed insulitis, which is characterized by leukocytic infiltration of the islets of Langerhans, and slowly evolves to its overt phase, when more than 90% of the b cells have been destroyed and insulin production is insufficient to regulate blood glucose levels As insulitis is asymptomatic, diabetes is often diagnosed during its overt phase and consequently, very little is known about its progression, in humans in particular We propose to test the hypothesis that the stratification of diabetes progression is reflected in physiologic changes occurring in the pancreas We will exploit recent advances in the fields of optical and magnetic resonance imaging (MRI), to develop and optimize novel techniques for the in vivo imaging of pancreatic inflammation These techniques will be established in well-characterized animal models of type 1 diabetes, including the nonobese diabetic (NOD) and the BDC2 5 T cell receptor (TCR) transgenic (tg) models, which exhibit spontaneous diabetes Subsequently, we will apply the developed

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technology in animal models of type 1 diabetes to address questions regarding the heterogeneity, progression and stratification of the disease and factors that control them. Such information will be invaluable for the detection, prevention and treatment of type 1 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL KINASE SIGNALING CASCADES IN PANCREATIC ACINI Principal Investigator & Institution: Williams, John A.; Professor; Physiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 24-JUN-1998; Project End 31-MAY-2003 Summary: Several major pancreatic disease including pancreatitis, cancer and cystic fibrosis involve altered cellular regulation. Secretion of digestive enzymes by pancreatic acinar cells is largely controlled by increases in intracellular Ca2+ and diacylglycerol which result from activation of phospholipase C. However, this mechanism can not explain all the effects of secretagogues and hormones on cell growth, protein synthesis and metabolism. Recently a number of novel protein kinase cascades have been elucidated that play important roles in growth, differentiation and gene expression of a variety of cells. We have shown in published and preliminary studies that CCK activates three mitogen activated protein kinase (MAPK) cascades in rat acini leading to activation of ERKs (p42 and p44 MAPK), Jun Kinase and p38/Reactivating Kinase. In addition, CCK activates a distinct pathway in acini leading to p70 S6 Kinase which is sensitive to rapamycin and wortmannin. The overall aim of this proposal is to understand how the novel kinase cascades are activated in acini, the specific stimuli which activate them, and some of their biological functions. Four specific aims include: 1) to determine the mechanism by which CCK and EGF activate the Ras-Raf-MEK-ERK cascade; the importance of the adapter proteins Sch and Grb2 as well as Ras will be evaluated. 2) To determine the tyrosine kinase activated by CCK which phosphorylates Shc. This will involve analysis of the activation of Src and Src family members and focal adhesion kinase (FAK). 3) To determine the activation of p38MAPK, its mechanism of activation, and its role in regulating phosphorylation of small heat shock protein, and 4) the mechanism of p70 S6K activation and its role in pancreatic acinar protein synthesis. The studies will involve immunoprecipitation of kinases, Western blotting and kinase assays using specific substrates. Selective pathway activation and inhibition using specific inhibitors and expression of dominant negative mutant proteins by adenoviral vectors will be used to evaluate pathways leading to biological effects including amylase secretion, growth and protein synthesis. While the work is aimed at understanding the pancreatic acinar cell, it will also have implications for the regulation of other gastrointestinal cell types. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL PROTEASE FORMULATION BASED ON CROSSLINKED CRYSTALS Principal Investigator & Institution: Shenoy, Bhami C.; Altus Biologics, Inc. 625 Putnam Ave Cambridge, Ma 021394807 Timing: Fiscal Year 2003; Project Start 01-JUL-2000; Project End 31-MAR-2005 Summary: (provided by applicant): Design of stable and efficient formulation of proteins for therapeutic use as drugs has been a major focus of biotechnology and pharmaceutical companies. In the Phase I grant, we developed a stable, active formulation of protease from Aspergillus melleus, TheraCLEC-Protease, for use in the

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treatment of chronic abdominal pain in chronic pancreatitis and also along with TheraCLEC-Lipase and amylase for the treatment of malabsorption as a result of pancreatic insufficiency in cystic fibrosis and chronic pancreatitis. TheraCLEC-Protease exhibited product characteristics superior to commercially available pancreatic enzyme products. TheraCLEC-Protease exhibited a very high level of activity against casein and stability under low pH and towards various proteases present in the intestine. Moreover, in the preliminary investigations, the TheraCLEC-Protease did not show any toxicity. Based on these results in Phase II, we will prepare a drug product prototype for use in the treatment of abdominal pain in chronic pancreatitis and along with TheraCLEC-Lipase for use in the treatment of pancreatic insufficiency, azotorrhea and steatorrhea in cystic fibrosis and chronic pancreatitis patients. As a first step, we will crystallize and crosslink the protease with methods developed in Phase I Subsequently, we will mix TheraCLEC-Protease with TheraCLEC-Lipase and amylase for use in a final formulation or alone depending on the disease and type of treatment. The final formulation will be tested for efficacy in digesting proteins and fats in dogs with ligated pancreatic ducts. Using radiolabeled TheraCLEC-Protease, we will follow the lack of absorption into the systemic circulation. In addition, we will test the subacute, subchronic and long-term effects of feeding TheraCLEC-Protease in two species. If successful, a TheraCLEC-Protease prototype will provide an efficient treatment for abdominal pain. TheraCLEC-Protease will be ready to enter clinical trials, and will provide a novel treatment for pancreatic insufficiency in chronic pancreatitis and cystic fibrosis along with TheraCLECLipase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE DAMAGE IN PANCREATITIS AND PANCREATIC NEOPLASIA Principal Investigator & Institution: Bell, Richard; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001 Summary: Carcinoma of the pancreas if the fifth leading cause of cancer death in the United States; treatment for established carcinoma is largely ineffective, with mean survival measured in months. The possibility of detection of early neoplasms in a highrisk group forms the rationale for the current proposal. Chronic pancreatitis is the most significant risk factor for pancreatic cancer yet identified. Acute and chronic pancreatitis are associated with injury from reactive oxygen radicals. Oxidative damage to DNA during the development of chronic pancreatitis may lead to mutations which ultimately cause the development of subsequent pancreatic cancer. The eventual fate of oxidatively damaged cells may depend on anti-oxidant defense against further injury, changes in the ability of cells to undergo apoptosis, or changes in cell proliferation. These further changes may be a result of continued oxidative damage. In the first specific aim of the current proposal, normal pancreas and tissue with chronic pancreatitis and pancreatic cancer will be examined for markers of oxidative DNA damage, antioxidant defense, apoptosis, and proliferation. The second specific aim will address whether oxidative damage sensitizes the pancreatic duct epithelium to further changes in antioxidant defense, apoptosis and proliferation. We will determine whether antioxidant treatment can prevent these changes. This aim will also determine if cells exposed to oxidative stress are more sensitive to carcinogen challenge than normal duct cells. To examine similar questions in an in vivo model, chronic pancreatitis will be induced in hamsters and the resultant oxidative damage in pancreatic tissue measured, as well as changes in antioxidant defense, apoptosis, and proliferation. These animals will be observed for the

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development of spontaneous tumors and tested for the development of cancer in response to low doses of the carcinogen N-nitrosobis (2-oxopropyl) amine (BOP). Animals with chronic pancreatitis will be treated with antioxidants during the course of pancreatitis will be analyzed for markers of oxidative damage, antioxidant defense, apoptosis or proliferation which are found to be associated with neoplastic change in Aims 1 and 2. Aim 2, we will establish the feasibility of measuring these markers in pancreatic juice and brushing, determine the incidence of marker positivity in patients with chronic pancreatitis, validate the markers, and develop a cohort of chronic pancreatitis patients for long=term cancer surveillance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PAIN RELIEF FROM ADL 10-0101 IN CHRONIC PANCREATITIS Principal Investigator & Institution: Eisenach, James C.; Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PANCREAS AND ISLET TRANSPLANTATION IN HUMANS Principal Investigator & Institution: Robertson, R Paul.; Scientific Director and Ceo; Pacific Northwest Research Institute 720 Broadway Seattle, Wa 98122 Timing: Fiscal Year 2001; Project Start 01-DEC-1988; Project End 31-JUL-2002 Summary: "The overall goal of the work described in this proposal is to fully understand the metabolic consequences of long term, successful pancreas and islet transplantation in Type 1 Diabetic patients and to ascertain the long term metabolic consequences of hemi pancreatectomy in healthy human donors. For recipients of pancreas transplantation, the two specific aims are: Specific Aim 1: To compare insulin secretory reserve in pancreas transplant recipients receiving either cyclosporin or FK 506 as immunosuppressive therapy. Specific Aim 2: To assess counter- regulatory responses of glucagon and epinephrine during hypoglycemic, hyperinsulinemic clamps pretransplant and longitudinally posttransplant and to ascertain whether differences in responses exist in patients receiving cyclosporin or FK506. For normal patients who have undergone hemi pancreatectomy to donate hemi organs to relatives, the two specific aims are Specific Aim 3: To assess glycemic regulation and insulin secretory reserve pre operatively and longitudinally post operatively in donors. Specific Aim 4: To assess insulin mediated glucose disposal, glucose mediated glucose disposal, and glycemic regulation pre operatively and longitudinally post operatively in healthy human donors. For type 1 patients receiving auto or allotransplantation of islets, the three specific aims are: Specific Aim 5: To correlate measurements of post transplant insulin secretory reserve with the number of islets autotransplanted in non diabetic chronic pancreatitis patients. Specific Aim 6: To compare glycemic regulation and insulin secretory reserve longitudinally in islet recipients receiving steroids or no steroid and cyclosporin or FK 506. Specific Aim 7: To assess glucagon responses during hypoglycemic, hyperinsulinemic clamps pre operatively and longitudinally in type 1 diabetic patients receiving alloislets. The research design and methods for achieving these goals will include measurements of glucose and hemoglobin AlC levels; insulin, C peptide, and glucagon secretion; hypoglycemic, hyperinsulinemic and euglycemic, hyperinsulinemic (with and without concurrent somatostatin infusion) clamps; and studies of glucose potentiation of arginine induced insulin secretion."

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

Project Title: PANCREAS TRANSCRIPTION FACTORS AND CANCER MODEL SYSTEMS Principal Investigator & Institution: Konieczny, Stephen F.; Associate Professor; Biological Sciences; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: (adapted from investigator's abstract): The development of the mammalian pancreas represents an attractive model system to study the molecular signals that direct the commitment and differentiation of epithelial cells along different cell lineages. The pancreas consists of two distinct tissue types which carry out different essential functions. The endocrine pancreas regulates blood sugar levels by secreting glucagon or insulin whereas the exocrine pancreas secretes digestive enzymes into the duodenal part of the small intestine. Although many of the transcription factors responsible for endocrine pancreas formation have been identified and extensively studied, the molecular regulatory circuits that control the establishment and maintenance of the exocrine pancreas are just beginning to be elucidated. Towards a goal of identifying key transcriptional regulators of pancreatic development and function, a novel basic helixloop-helix (bHLH) transcription factor (Mistl) recently was identified that accumulates to high levels in pancreatic exocrine cells. Mistl gene expression is initially detected at mouse embryonic day E10.5 in the developing pancreas and remains expressed to high levels in the acinar cells of the adult. Although the Mistl nuclear protein is capable of binding to specific DNA targets as a homodimer or as a heterodimer with other bHLH transcription factors, it lacks a typical transcription activation domain and instead can serve as a transcriptional repressor in some experimental systems. At this time, a true role for Mistl activity in pancreatic function has not been established, although its expression pattern and DNA binding capabilities suggest that Mistl likely serves as a key regulator of exocrine pancreas gene activity. In order to characterize further the biochemical properties of the Mistl protein and the role of Mistl in pancreatic development, studies are proposed to (1) examine the activity of Mistl using a pancreatic cell line model system, (2) identify pancreas-specific Mistl protein binding partners and (3) utilize mouse genetic approaches to create Mistl homozygous null mice and to identify Mistl target genes. In addition, targeted replacement of the Mistl gene with an activated K-ras allele will be performed to generate novel pancreatic cancer models. A complete characterization of Mistl activity in exocrine pancreatic cells will add critical new information regarding normal pancreatic development and function and may provide future strategies for combating several key human diseases, including acute pancreatitis and pancreatic cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PANCREATIC DEVELOPMENT IN MODELING PANCREATIC DISEASE Principal Investigator & Institution: Grippo, Paul J.; Surgery; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): The Role of Pancreatic Development in Modeling Pancreatic Disease in Mice. September 4-5, 2003 Northwestern University and Northwestern Memorial Hospital The pancreas serves both an endocrine and exocrine function and has distinct roles in glucose homeostasis and digestion. Several debilitating

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diseases, with virtually no curative measures, arise when cell types undergo genetic mutations, altering cell function and/or inducing cellular transformation. Diabetes, pancreatitis, and pancreatic cancer have serious health consequences beginning with a greatly reduced quality of life and ending in death. These diseases are associated with each other. For example, people with diabetes and/or pancreatitis have a greater incidence of pancreatic cancer. In order to introduce curative paradigms against these diseases, it is critical to evaluate therapies outside the clinic, which include using animal models that recapitulate these human diseases. A few mouse models do exist for these diseases yet seldom do these models provide phenotypic or molecular mimicry to their human counterpart. To better understand the sequential genetic and cellular events that lead to diabetes, pancreatitis, and pancreatic cancer and engineer models for therapeutic evaluation, it becomes critical to understand the underlying mechanisms responsible for differentiation and cell fate. Evidence is accumulating on the pathway from a progenitor cell type to the three primary cells of the pancreas: islet, acinar, and ductal cells. In order to improve pancreatic development and disease modeling research, I propose holding a conference that brings both groups together. I am hoping to foster a critical link that is not entirely in place. That link is between scientists exploring pancreatic development and the signals that determine differentiation patterns and cell fate with those investigators who desire to model pancreatic disease in mice. New information that defines which embryonic cell(s) and/or cell signal(s) that are responsible for generating mature endocrine and exocrine cells in the pancreas is critical for engineering new transgenic mouse models that recapitulate diabetes, pancreatitis, and pancreatic cancer. Targeting pancreatic progenitor cells with various genetic alterations will provide valuable information for the developmental biologist and clinical pathologist alike. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PH II STUDY RECOMBINANT PLATELET ACTIVATING FACTOR ACETYLHYDROLASE Principal Investigator & Institution: Slivka, Adam; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001 Summary: The objectives of this study are: 1)to determine if the prophylactic administration of rPAF-AH decreases in incidence and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in a dose-dependent manner. 2)to evaluate the cost-efficacy of rPAH-AH when administered prophylactically to prevent post-ERCP pancreatitis. 3)to characterize the safety and pharmacokinetic behavior of rPAH-AH after intravenous administration in patients scheduled to undergo ERCP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PANCREATITIS

PHARMACOGENETICS

OF

ASPARAGINASE-INDUCED

Principal Investigator & Institution: Silverman, Lewis B.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): We seek to determine whether there is a genetic predisposition for the development of asparaginase-related pancreatitis. Asparaginase is a highly effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with significant side effects in up to one-third of patients.

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Patients who are unable to receive all of their intended doses of asparaginase have a higher relapse rate than those who are able to tolerate all or nearly all of their doses, with a 5-year event-free survival rate of 73% for asparaginase-intolerant and 90% for asparaginase-tolerant patients (p<0.01). The most common cause of asparaginase intolerance is pancreatitis. The mechanism of asparaginase-induced pancreatitis is unknown. Recent studies suggest that genetic factors predispose to several types of pancreatitis, including chronic idiopathic and alcohol-induced pancreatitis. Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been associated with pancreatitis in people without cystic fibrosis. We hypothesize that children with ALL who have germline mutations of CFTR might be at increased risk for the development of asparaginase-related pancreatitis. The proposed investigations bring together two groups, one with expertise in asparaginase and the treatment of ALL and the other with expertise in the analysis of CFTR gene mutations/variations, in order to determine whether there is a pharmacogenetic relationship between CFTR gene mutations and the development of asparaginase-related pancreatitis. The frequency of CFTR gene mutations will be compared in children with ALL who had asparaginaserelated pancreatitis and similarly treated children who did not. The finding of an association between asparaginase-related pancreatitis and CFTR gene mutations would make an important contribution to the understanding of the pathophysiology of drugrelated pancreatitis. Additionally, because potential therapeutic interventions for CFTRmediated pancreatitis are becoming available, the finding of an association might also lead to effective therapy for this currently untreatable form of pancreatitis. Prevention or treatment of asparaginase-induced pancreatitis could result in more children receiving all of their intended doses of asparaginase, potentially both reducing toxicity and enhancing efficacy of treatment for children with ALL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT--NON OXIDATIVE ALCOHOL METABOLITES PRIME PANCREAS FOR INFLAMMATORY INJURY Principal Investigator & Institution: Gukovskaya, a; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001 Summary: The overall goal of the project is to determine the mechanisms of ethanol toxicity to the pancreas which mediate pancreatitis, a poorly understood and treated disorder with alcohol abuse as a major cause. The work proposed in the application is designed to determine the pathways of ethanol metabolism in pancreatic acinar cells and the mechanisms whereby ethanol metabolites mediate pancreatic acinar cell injury. We hypothesize that pancreatic acinar cell produces non-oxidative (fatty acid ethyl esters, FAEEs) and oxidative (acetaldehyde and acetate) ethanol metabolites. The ethanol metabolites, in turn, activate transcription factors, such as NF-kappaB and AP-1. The transcription factors activate the expression of cytokines that are responsible for inflammation, cell death, and fibrosis, the main characteristics of ethanol-induced pancreatitis. We propose the following specific aims: 1. Measure non-oxidative and oxidative ethanol metabolism in dispersed rat pancreatic acini and hepatocytes by measuring the activities of FAEE synthase, alcohol dehydrogenase, aldehyde dehydrogenase, the formation of FAEEs, acetaldehyde, and acetate in pancreatic acini incubated with ethanol for different times; and the intracellular localization (cytosol, microsomes) of the ethanol metabolism. 2. Determine the effects of ethanol, FAEEs, acetaldehyde, and acetate on the activation of transcription factors NF- kappaB and AP1 in dispersed pancreatic acini 3. Determine the effects of ethanol. FAEEs, acetaldehyde

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and acetate on the expression of cytokines TNFalpha, IL-1, IL-6, and TGFbeta in dispersed pancreatic acini. 4. Measure non-oxidative and oxidative ethanol metabolism in pancreatic tissue from rats fed ethanol by intragastric infusion for different period of time. To accomplish these goals, we will perform the following measurements on rat pancreatic acinar cells and hepatocytes, measurements of the activities of alcohol dehydrogenase, aldehyde dehydrogenase, FAEE synthase in crude cell homogenate and cell fractions using enzyme assays; FAEE and acetate accumulation in intact cells using thin layer and ion-exchange chromatography; transcription factor activation using electromobility shift assays: expression of cytokines/chemokines using quantitative RTPCR. The result of the experiments described in this application will be the identification of key mechanisms of ethanol toxicity for pancreatic acinar cells that can be targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEASE INHIBITOR RELATED DYSLIPIDEMIA Principal Investigator & Institution: Wanke, Christine A.; Associate Professor; Family Medicine & Cmty Health; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 12-JUL-2000; Project End 30-JUN-2005 Summary: Protease inhibitors are used as therapy in HIV patients and have been reported to cause elevations in plasma triglycerides, cholesterol, and glucose, and rarely to induce severe hypertriglyceridemia, pancreatitis, and diabetes mellitus with insulin resistance, excess fat deposition, and lipodystrophy. Our aims are to measure fasting Serum cholesterol (C), triglyceride (TG), remnant lipoprotein (RLP) C and TG, low density lipoprotein (LDL) C, high density lipoprotein C, lipoprotein(a), apolipoproteins A-I and B, apo E genotype, homocysteine, free fatty acids, glucose, insulin, and blood pressure. We will also assess smoking status, carotid artery wall thickness by ultrasound, and coronary artery calcification by computerized tomography in our prospective cohort of 400 HIV patients whose nutritional status is being evaluated and who are taking a variety of antiviral agents including protease inhibitors. Comparisons will be made on and off inhibitors and also longitudinally, and with controls. Our comparison group are participants in the Framingham Offspring Study who have had all the same parameters measured (n=3250). HIV patients who become hyperlipidemic on protease inhibitors will be treated with either gemfibrozil or atorvastatin. We will also examine the effects of protease inhibition in Hep G2 and CaCo2 cells with or without supplementation with fatty acids and cholesterol on lipoprotein assembly and secretion and apolipoprotein, LDL receptor, and microsomal transfer protein (MTP) gene expression. The effects of protease inhibition on lipoprotein metabolism and aortic foam cell formation will also be assessed in F1B hamsters on chow and on diets high in cholesterol and saturated fat. In addition, using a primed constant infusion in the constantly fed state and deuterated leucine, the secretion and catabolism of apoB-48 and apoB-100 within lipoproteins will be determined by GC/MS analysis and multicompartmental modeling in the presence or absence of protease inhibition with ritonavir in 10 males and 10 female HIV patients. We will test the following hypothesis: 1) protease inhibitors increase triglyceride and cholesterol by increasing RLP; 2) elevated RLP leads to increased carotid wall thickness and coronary calcification; 3) these increases can be ameliorated with diet, gemfibrozil and/or atorvastatin treatment; 4) in cell culture these RLP increases are elated to enhanced secretion of apo B-100 due to less intracellular degradation, and excess cellular lipid content; 5) in hamsters there are increased RLP in serum in animals on the atherogenic diet, especially with protease inhibition, and this leads to increased aortic foam cell formation; 6) in humans protease

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inhibition causes increased triglyceride-rich lipoprotein apo B-100 secretion. This research should define the nature of the problem, its mechanism, and methods for treatment wit regard to the hyperlipidemia induced by protease inhibitors in HIV patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEASE-ACTIVATED RECEPTORS IN INFLAMMATION Principal Investigator & Institution: Coughlin, Shaun R.; Professor; Cardiovascular Research Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 01-JAN-1998; Project End 31-MAR-2007 Summary: (provided by applicant): The long term goal of this proposal is to define the role of protease-activated receptors (PARs) in inflammatory responses. PARs mediate cellular responses triggered by coagulation proteases and other proteases that are generated or released at sites of tissue injury. The effects of PAR activation in different cell types, largely defined in culture, suggest that PARs may help orchestrate a coordinated response to tissue injury that includes hemostasis, inflammation, and perhaps even regulation of the adaptive immune response. Local PAR activation by proteases generated at sites of local bacterial inoculation may protect against spread of bacteria by promoting both recruitment of leukocytes and microvascular thrombosis. However, more regional or systemic activation of PARs as may occur in the setting of tissue ischemia or sepsis may promote tissue damage by the same mechanisms. Toward testing these hypotheses, we have generated knockout mice for the known PARs as well as relevant double knockouts. Par4 -/- mice, for example, have no platelet responses to thrombin. Mice lacking both PAR1 and PAR4 may have lost thrombin signaling in all cell types. Using such mice and cells derived from them, we shall determine which PARs are responsible for mediating responses to coagulation proteases and other proteases in endothelial and other cell types, the extent to which different PARs in the same cell serve redundant functions, and the potential roles for endothelial PAR activation in vivo. We shall then go on to determine the effects of loss of PAR function in models of a) local bacterial infection and dissemination of same, b) systemic inflammatory response syndromes induced by endotoxin and by pancreatitis, and c) ischemia/infarction. Endpoints will include survival; markers of platelet and fibrin deposition and leukocyte accumulation in tissues; vascular permeability and edema; cytokine production; organ histology; and in a hind-limb ischemia-reperfusion model, reflow and infarct size. Lastly, because PARs sense tissue injury and hence "immunological danger," we shall ask whether PARs influence the decision to mount an adaptive immune response. These studies may point to new strategies for modulating injurious inflammatory responses in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RAIT OF PANCREATIC CANCER WITH HUMANIZED PAM4 Principal Investigator & Institution: Sharkey, Robert M.; Director, Clinical Research Administrati; Garden St Cncr Ctr/Ctr Mol Med & Immunol for Molecular Med & Immunology Belleville, Nj 07109 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): The primary aim of this proposal is to initiate a Phase I clinical trial that will explore the safety and possible efficacy of a single intravenous injection of 90Y-humanized PAM4 IgG in pancreatic cancer patients. PAM4

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is a monoclonal antibody directed against a unique epitope found on the human tumorassociated antigen, MUC1 that is well expressed in pancreatic cancer. The antibody does not react with normal pancreas and has limited reactivity with pancreatitis. Preclinical studies have shown that radiolabeled PAM4 is targeted to a high degree to pancreatic tumor xenografts, and 90Y-PAM4 is a highly effective therapeutic agent in these models. Very importantly, these preclinical studies show that 90Y-PAM4 can be combined with gemcitabine, the only FDA-approved chemotherapeutic agent for pancreatic cancer, to improve the therapeutic response of gemcitabine. Indeed, once this trial is completed, our primary objective will be to develop a treatment strategy for adding 90Y-hPAM4 to a standard gemcitabine treatment regimen. PAM4 has been humanized and this proposal is designed to initiate clinical studies with this antibody, radiolabeled with 111In for use in external scintigraphy as a surrogate for 90Y-hPAM4 that will be used in therapy. The clinical trial will be initiated within 6 months of funding, allowing time to complete the Points to Consider and obtain an IND. The trial is designed to first test a suitable protein dose for hPAM4 to be used in the next step of clinical testing, namely a determination of the maximum tolerated dose for 90Y-hPAM4. All patients will have a pre-therapy imaging/pharmacokinetic/dosimetry study performed with 111In-hPAM4 IgG. This study will be used to predict the behavior of the 90Y-hPAM4 IgG that will be given one-week later. All patients will be treated with 9xY-hPAM4 IgG, but in the first step, the 90Y-hPAM4 IgG will be fixed at a dose of 10 mCi/m2. Three dose cohorts are planned in the first step at 5 mg, 15 mg/m2 and 50 mg/m2. Once a suitable protein dose is selected, in the second step, escalation of the 90Y-hPAM4 radioactivity will proceed, starting at 15 mCi/m2 and escalating in 5 mCi/m2 increments until the MTD is determined. The trial design reflects early discussions with the FDA concerning an appropriate trial design for a new antibody. The trial will be conducted at the Garden State Cancer Center and Johns Hopkins University School of Medicine. CMMI will be responsible for monitoring the study's progress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION MACROGLOBULIN

OF

GROWTH

FACTOR

ACTIVITY

BY

A2

Principal Investigator & Institution: Gonias, Steven L.; Professor; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-MAY-2006 Summary: (Applicant's Description Verbatim): This research program focuses on the function of alpha2-macroglobulin (a2M) as a regulator of growth factor activity. a2M binds diverse growth factors with limited sequence identity, including transforming growth factor-n (TGFB), platelet-derived growth factor-beta (PDGF-beta), and nerve growth factor-B (NGF-f3). In cell culture, a2M antagonizes growth factor activity. Similar interactions may explain abnormalities in a2M gene knock-out mice that are challenged with inflammatory stimuli. By analyzing a library of a2M peptide-GST fusion proteins, we identified a sequence (an 591-774), near the center of the a2M subunit that binds TGF-B, PDGF-BB, and NGF-B with high affinity. A 16-amino acid peptide (P3) that binds both TGF-beta and PDGF-BB was subsequently identified. In the next five years, our major objectives are: to fully characterize a2M-growth factor interactions on a molecular level; to determine whether the function of a2M as a growth factor-binding protein is responsible for abnormalities in the a2M gene knock-out mouse; and to explore strategies for using our novel growth factor-binding peptides as therapeutics in cancer. Four specific aims are proposed. In Specific Aim 1, the function of P3 and related peptides as regulators of growth factor activity will be determined. In

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Specific Aim 2, the sequence of human aM will be modified by site-directed mutagenesis to determine the function of the P3 region in the intact protein. In Specific Aim 3, novel transgenic mice that express mutated forms of murinoglobulin will be generated. Crossbreeding experiments will then be performed with the a2M gene knock-out mouse to determine whether the phenotype of the a2M gene knock-out mouse can be rescued by reversing the deficiency in growth factor regulation. Finally, in aim 4, we will assess the ability of naturally-occurring a2M and a2M-derived growth factor-binding peptides to limit cancer growth and metastasis. The emerging function of a2M as a regulator of diverse growth factors indicates that this protein may have undiscovered activities in a variety of disease states. The combination of approaches proposed here, including molecular analyses and physiology studies, offers the opportunity to elucidate the function of a2M in various diseases including cancer and to exploit this knowledge in rational drug design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE FOR VIRAL INFECTION IN ALCOHOLIC PANCREATITIS Principal Investigator & Institution: Jerrells, Thomas R.; Professor; Pathology and Microbiology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): A large proportion of the cases of pancreatitis in human beings are associated with alcohol consumption, but pancreatitis develops in only a minority of people who abuse alcohol. These observations support the argument that factors other than alcohol or alcohol metabolisms are involved in the development of alcoholic pancreatitis. The hypothesis that will be investigated by the research proposed in this exploratory/developmental grant application is that one co-factor for the development of acute and chronic alcoholic pancreatitis is an infection with a virus that has a tropism for the pancreas. This viral infection is hypothesized to initiate the damage in the pancreas and this damage is more severe in individuals who abuse alcohol through an alcohol-associated sensitization of the pancreas. A murine model of alcohol consumption that is done with the use of C57BL/6 and Balb/c mice provided ethanol (ETOH) in either a liquid diet or in the drinking water will be used for these studies. Specifically, mice provided ETOH and control mice (i.e., pair-fed and chow-fed) will be infected with coxsackievirus group B, stereotype 3 (CVB3) and pancreas damage and fibrosis will be evaluated. The hypotheses will be addressed by three specific aims: 1) To develop the model system to characterize the effects of ETOH and CVB3 infection of the pancreas; 2) To determine the effect of ETOH consumption on production of proinflammatory cytokines during the viral infection; 3) To determine the effects of chronic ETOH consumption, with an ETOH-in-drinking-water model system, on pathologic effects in the pancreas after viral infection. The development and characterization of this model system will provide a useful model of alcoholic pancreatitis that will allow follow-up studies to investigate mechanisms of ETOH to sensitize the pancreas to damage. The model system will also allow critical studies of possible therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE PATHOGENESIS

OF

CCK

RECEPTOR

IN

ACUTE

PANCREATITIS

Principal Investigator & Institution: Samuel, Isaac; Surgery; University of Iowa Iowa City, Ia 52242

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Pancreatitis

Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 30-NOV-2007 Summary: (provided by applicant): Acute pancreatitis is a common disease with significant morbidity and mortality but no specific treatment is available as the pathogenic mechanisms are not known. The purpose of this research proposal is to elucidate early events in pathogenesis of gallstone-induced acute pancreatitis. We use the rat model of bile-pancreatic duct ligation-induced acute pancreatitis as an experimental corollary. Bile-pancreatic juice exclusion from gut causes feedback exocrine pancreatic stimulation via cholecystokinin-A receptor (CCK-AR) mechanisms. The role of the CCK-AR in disease pathogenesis is not known. Our preliminary studies provide the first evidence that CCK-AR mediated pancreatic acinar cell hyperstimulation plays a contributory role in disease pathogenesis and that induction of CCK-AR occurs within one hour of duct ligation. We hypothesize that pathological amplification of CCK-AR mediated signal transduction exacerbates disease pathogenesis. We propose experiments to test this hypothesis and pursue these specific aims: 1) Characterize the role of the CCK-AR in duct occlusion-induced acute pancreatitis pathogenesis. 2) Characterize the expression and regulation of the CCK-AR in duct occlusion-induced acute pancreatitis. 3) Characterize the CCK-AR mediated signal transduction pathway in duct occlusion-induced acute pancreatitis. Competitive binding assays with radiolabeled ligand will be done to study receptor number, specificity, and affinity. Receptor sensitivity and activity will be determined by measuring downstream signals (cyclic AMP, inositol phosphate). Differences between the induced and native receptor will be determined both in terms of altered functional characteristics and perturbations in intracellular signal transduction pathways. The possibility that promiscuous G-protein coupling in acute pancreatitis could drastically increase CCK-AR affinity and also perpetuate a grossly amplified intracellular signal may have profound implications in mechanisms of disease pathogenesis. An innovative feature of this proposal is the use of an original surgical model, "The Donor Rat Model", that provides a unique opportunity to investigate disease pathogenesis. The significance and health-relatedness of this research endeavor is its ultimate goal to elucidate mechanisms of disease pathogenesis that provide the rationale to base new treatment protocols intended to reduce the morbidity and mortality of acute pancreatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF CD40 IN SEPSIS-INDUCED LUNG INJURY Principal Investigator & Institution: Gold, Jeffrey; Pediatrics; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Acute lung injury (ALI) is a major health problem that is characterized by exudation of fluid into the alveoli and release of proinflammatory cytokines. It is frequently the result of a systemic inflammatory process including sepsis, trauma, hemorrhage and pancreatitis. We have used the cecal ligation and puncture (CLP) model of sepsis to study the importance of the cell surface molecule CD40 in development of ALI in mice. We now report that CLP produces lung capillary leak, interstitial infiltration of inflammatory cells and 30 percent morality at 18 hours. Matched mice with deletion of CD40 have marked attenuation of lung inflammation and 0 percent mortality at 18 hours. CD40 mutation also markedly attenuates production of anti-inflammatory IL-10 and proinflammatory IL-6 and IL-12 in both serum and broncho-alveolar lavage (BAL) after CLP. CD40 knockout (KO) mice also have a reduction of pro-inflammatory NfkB and anti-inflammatory C/EBPB and STAT3 transcription factors after CLP in both the lung and liver. Although capable of

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attenuating both pro and antiinflammatory signals, attenuation of inflammation predominates in mice deficient in CD40. Mice with a conditional mutation of STAT3 only in macrophages and NK cells (STAT3 KO) have a marked increase in cell surface CD40 expression on alveolar macrophages (AM) but not lymphocytes at baseline. These mice have a more severe ALI after sublethal CLP as evidenced by histologic appearance. This is associated with a marked increase in IL-6, IL-10 and IL-12 production in serum and BAL. Conversely, STAT3 wild type mice had no alterations in either lung histology or cytokine levels after CLP induced sepsis. These data raise the possibility that AM CD40 expression is a central regulator of lung injury during sepsis. We hypothesize that development of ALI depends upon the balance between pro and anti-inflammatory transcription factors. By controlling induction of these transcription factors, AM expression of CD40 is necessary to fully develop ALI during sepsis. We propose to determine the ability of CD40 to modulate pro and anti-inflammatory transcription factor induction in macrophages (STATI and STAT3 respectively) after CLP induced sepsis, better define the role of STAT1 and STAT3 in feedback regulation of CD40 expression and define the utility of CD40 blocking agents for the treatment of sepsis induced ALI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEM CELLS: POTENTIAL THERAPEUTICS FOR ALCOHOL ABUSE Principal Investigator & Institution: Hipp, Jason D.; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2003; Project Start 29-FEB-2004 Summary: (provided by applicant): Alcohol abuse and alcoholism remain a serious societal problem. In addition to better understanding the basic biobehavioral mechanisms of the disease, it is very important to begin developing clinical interventions to address issues of end-stage pathology. Long-term alcohol abuse induces a panoply of systems failure including alcoholic liver disease, cardiomyopathy, neuronal death associated with alcohol-induced dementia, and pancreatitis. One potential approach will be to develop new stem cell technologies to provide therapeutic tools to reverse these pathologies. In order to realize this goal, however, detailed knowledge will be required of host acceptance of syngeneic and allogeneic grafts, the effects of alcohol on selective stem cell differentiation, and the effects of genetic imprinting. The present application will utilize a new source of primate stem cells - derived from parthenogenetic activation of non-human primate oocytes - to examine these specific issues. The parthenote-derived stem cell represent a novel resource, created in these laboratories, for the generation of new cellular tools for correcting the pathophysiology associated with alcohol abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURGICAL APPROACH TO EXPERIMENTAL PANCREATITIS Principal Investigator & Institution: Nathan, Jaimie D.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: Acute pancreatitis carries significant morbidity and mortality. The cellular mechanisms that underlie the inflammatory process are poorly understood, and effective treatment of acute pancreatitis is unavailable. Neurogenic inflammation has been implicated in the evolution of acute pancreatitis. In other inflammatory diseases, substance P is released from primary sensory nerve endings by activation of the

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capsaicin receptor, vanilloid receptor subtype 1 (VR1), and triggers neurogenic inflammation by acting via the neurokinin-1 (NK-1) receptor on target cells. The severity of experimental pancreatitis is markedly reduced in NK-1 receptor-deficient mice, suggesting a proinflammatory role for the NK-1 receptor in acute pancreatitis. The hypothesis to be tested is that neurogenic inflammation contributes to the evolution of acute pancreatitis and is mediated by substance P release from primary sensory nerve endings. The following specific aims will be addressed in caerulein-induced experimental pancreatitis: (1) to demonstrate that the proinflammatory role of NK-1 receptors results from binding of substance P, (2) to determine by pharmacological and by surgical manipulations whether primary sensory afferent neurons are the source of substance P release, (3) to determine whether substance P release is mediated by activation of VR1. The severity of pancreatitis will be assessed by biochemical assays and histological examination following pretreatment with an NK-1 receptor antagonist, with capsaicin, and with a VR-l antagonist, and following dorsal rhizotomy. NK-1 receptor immunolocalization will be performed to assess binding of substance P. Elucidation of the mechanisms of neurogenic inflammation in acute pancreatitis may result in improved treatment modalities for this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURGICAL STUDIES OF PANCREATIC STEM CELLS Principal Investigator & Institution: Leach, Steven D.; The Paul Neumann Professor in Pancreatic; Surgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 30-JUN-2004 Summary: Pancreatic ductal proliferation is a frequent hallmark of surgical pancreatic disease. However, the epithelial stem cells responsible for pancreatic duct proliferation remain unknown. The long-term objective of this research program is to identify the "cell of origin" from which ductal proliferation originates during chronic pancreatitis and pancreatic cancer, potentially allowing therapeutic intervention to be directed to precursor cells. Using both surgical and transgenic models of ductal proliferation, preliminary experiments have been performed suggesting that pancreatic stem cells can be identified based on the following criteria: 1) ductal location, 2) enhanced proliferative capacity, 3) expression of the anti-apoptotic protein Bcl-2, and 4) expression of the Pdx1 and Pax6 homeobox transcription factors. Based on these studies, the following specific aims are proposed: First, to characterize the role of Pdx1- and Pax6- expressing pancreatic stem cells in benign pancreatic ductal proliferation induced by surgical pancreatic duct ligation. Second, to characterize the role of Pdx1- and Pax6-expressing stem cells in premalignant pancreatic duct proliferation induced by TGFalpha overexpression in MT-TGFalpha transgenic mice. Third, to isolate and propagate Pdx1expressing pancreatic stem cells in long-term tissue culture, and to investigate the effects of TGFalpha and transforming oncogenes on their growth and differentiation. These investigations will be pursued utilizing a novel in vivo reporter gene approach which takes advantage of pre-existing mouse lines in which one copy of either the endogenous Pdx1 locus or the endogenous Pax6 locus has been replaced with a lacZ cassette. This allows precise tracing of candidate stem cells expressing these homeobox genes. In addition, a strategy for isolation of pancreatic stem cells is proposed using the Pdx1 promoter to target expression of the neomycin antibiotic resistance gene to the embryonic pancreatic ductal epithelium. Together, these investigations will provide important new insight regarding the pancreatic cell lineages participating in ductal proliferation, and potentially lead to novel therapeutic strategies for surgical pancreatic disease.

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

Project Title: SURGICAL STUDIES ON METABOLISM OF GI HORMONES Principal Investigator & Institution: Gomez, Guillermo; Surgery; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-MAY-1976; Project End 30-APR-2004 Summary: A major challenge in gastrointestinal research today is to gain a better understanding of the underlying molecular mechanisms for maintenance of the exocrine pancreas and small bowel mucosa. Acute pancreatitis (AP) is a complex and poorly understood disease. Severe acute hemorrhagic or necrotizing pancreatitis in humans results in an exceptionally high morbidity and mortality. Despite the abundance of pancreatitis patients, underlying molecular mechanisms that control the severity of an AP are not known. Likewise, a deficiency in appropriate intestinal regeneration or adaptation following mucosal disease or injury can be clinically relevant. The specialized epithelial cells of the small bowel mucosa constitute an essential organ for nutrient absorption, immune function and regulation of fluid and electrolyte balance. Disruption of the integrity of the intestinal mucosa either through inflammation, infiltration, surgical resection or ischemia results in severe malabsorption and ultimately in clinical malnutrition requiring total parenteral nutritional support. The long term objectives of the proposed work are to understand the roles gastrointestinal (GI) hormones play in the homeostasis of the pancreas, and in controlling GI epithelial restitution and regrowth. The Specific Aims of this research proposal are: 1) to determine the role of gastrointestinal hormones in the regulation of pancreatic apoptosis and regeneration in experimental models of acute pancreatitis; and, 2) to determine the role of gastrointestinal hormones in the regulation of adaptive hyperplasia of the gut. The proposed studies are designed to precisely define, in a systematic fashion, the components of GI hormone-linked intracellular transduction pathways involved in the regulation of pancreatic apoptosis and regeneration in experimental models of AP; and, the proliferation of GI mucosa associated with adaptive hyperplasia of the gut. In order to accomplish these aims, we will investigate molecular pathways of acinar cell proliferation and apoptosis in three different models of experimental AP, and the intracellular signal transduction pathways mediating the regulation of neurotensin gene expression by insulin-like growth factor-I (IGF-I) and the enhancement of glucagon-like peptide-2 (GLP-2)- stimulated mucosal proliferation by neurotensin. These studies will provide a foundation for the development of innovative therapeutic strategies designed to exploit the unique biological activities of GI hormones on the exocrine pancreas and intestinal mucosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURGICAL STUDY OF PANCREATIC TGFBETA-MEDIATED SIGNALING Principal Investigator & Institution: Simeone, Diane M.; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 28-FEB-2008 Summary: (provided by applicant): Recent evidence indicates that perturbations in the TGFbeta signaling pathway plays a crucial role in the development of surgical pancreatic disease, including pancreatic cancer and pancreatitis. However, the mechanisms of TGFbeta signaling in the human pancreas are largely unknown. This lack of basic information is a major obstacle to rational treatment of human pancreatic

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diseases, and is reflected in the current empiric, and often ineffective treatment of human exocrine pancreatic cancer and pancreatitis. Recently, we have identified a novel signaling pathway for TGF[3 in the pancreas whereby the obligate second messengers of the TGFbeta signaling pathway, the Smads, activate protein kinase A (PKA) in pancreatic acinar cells. This may represent an important mechanism of crosstalk within the acinar cell. Our preliminary data demonstrates a novel interaction of Smads and the regulatory subunit of PKA within pancreatic acinar cells, and also suggests that PICA may mediate growth inhibitory responses induced by TGFbeta. Therefore we hypothesize that TGF's physiological effects on growth are mediated by Smads and their interactions with the PKA signaling pathway. This research proposal is designed to investigate the molecular basis for the interaction of TGFI3 signaling molecules with the PKA signaling pathway. The experiments will address the hypothesis that Smads3 and 4 directly bind to and activate PKA by a previously unidentified, cAMP-independent mechanism, and will determine interaction domains of Smads 3 and 4 and the regulatory subunit of PKA. In addition, we will investigate the role of PKA in TGFbetamediated growth inhibition in pancreatic acinar cells. The proposed research integrates physiological studies with novel molecular strategies, an approach likely to reveal important new insights. The long term goal of this project is to gain a detailed understanding of TGF signaling mechanisms in the pancreas that may be of benefit in the treatment and/or prevention of human pancreatic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNTHESIS AND ACTIVITY OF NOVEL KAPPA OPIOID PEPTIDES Principal Investigator & Institution: Bennett, Marco A.; Pharmaceutical Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-OCT-2001 Summary: (provided by applicant) Dynorphin A, an endogenous neuropeptide, is has high affinity and selectivity for the kappa opioid receptors. It has been reported that the N-terminus ?message? sequence is important for kappa opioid receptor activation while the ?address? sequence is designated as the potency-enhancing domain responsible for the high specificity of dynorphin A. Two novel lead Dyn A analogues, arodyn (aromatic dynorphin), and JVA-901, have displayed different structure-activity relationships from Dyn A. It is therefore hypothesized that arodyn and JVA-901 bind differently to the kappa opioid receptors. The goal of this research proposal is to identify potent and selective kappa opioid receptor antagonists. To pursue this goal novel selective kappa receptor antagonists will be designed utilizing classic and combinatorial peptide libraries and evaluated using Chinese hamster ovary cells stably expressing opioid receptors. The combination of classical and combinatorial approaches will be used to modify the sequences of the two aforementioned lead peptides and generate focused peptide libraries. Combinatorial peptide libraries offer the advantage of synthesizing a variety of peptides simultaneously and allows the introduction of various combinations of amino acids in the sequence of arodyn and JVA-901. Syntheses will be done using solid phase peptide synthesis. There are many potential clinical applications of kappa agonists and antagonists, including the prevention of pancreatitis, neuroprotection (epilepsy) and anti-convulsants, potential treatment in cocaine abuse and opioid dependence as well as use in pharmacological assays as pharmacological tools to help understand kappa receptor-ligand interactions at the molecular level since kappaselective peptide antagonists are limited. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE CALCIUM-SENSING RECEPTOR IN ACUTE PANCREATITIS Principal Investigator & Institution: Saunders, Christine; Biochemistry; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 30-NOV-2003 Summary: (adapted from the application) Acute pancreatitis is an inflammatory disease with significant mortality, affecting about 80,000 Americans a year. The pathophysiologic mechanisms are not thoroughly elucidated, and to date there are few if any effective treatments. Calcium and lipid mediators are integral components of the signaling cascade involved in pancreatic inflammation. Changes in blood calcium levels have been associated with acute pancreatitis, both in humans and in laboratory animals. The recently cloned calcium-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), by virtue of its ability to stimulate inflammatory lipid mediator synthesis, provides a possible mechanism for how calcium, lipid mediators and acute pancreatitis are linked. In fact, recent findings suggest that the CaSR in the pancreas is upregulated during acute pancreatitis in the rat. The hypothesis for the proposed studies is that the pancreatic CaSR is involved in initiating and/or propagating acute pancreatitis by activating PLA2, which stimulates lipid mediators involved in the inflammatory cascade. In this proposal, molecular biologic, biochemical and physiologic approaches will be combined to investigate the role of the pancreatic CaSR in experimental acute pancreatitis. The secretagogue (eg. cerulein) hyperstimulation model in rats is a well established model in which hourly administration of high doses of cerulein for 6 hours induces an edematous acute pancreatitis. Multiple techniques will be used to test the hypothesis by addressing the following specific aims: (1) to identify the pancreatic cells which express the functional CaSR; (2) to determine whether the CaSR is directly involved in acute pancreatitis in the rat; (3) to examine whether cytoskeletal depolymerization during acute pancreatitis provides a mechanism for how the CaSR is upregulated in cerulein-induced pancreatitis; (4) to examine whether there is "crosstalk" between the cholecystokinin A (CCK-A) receptor and the CaSR which might lead to activation of the CaSR in cerulein-treated rats. While the role of the CaSR in inherited diseases is emerging, its function in inflammatory conditions remains unknown. Since the CaSR activates lipid mediator synthesis, its potential role in inflammation seems logical and represents an exciting and novel possibility. Also, this study might serve as a paradigm for inflammatory conditions other than pancreatitis, the treatments for which have remained elusive. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE INFLAMMATORY RESPONSE OF THE PANCREATIC ACINAR CELL Principal Investigator & Institution: Pandol, Stephen J.; Scientist; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): The pancreatic acinar cell has served as a cell biologic model for determining the mechanisms of protein synthesis, transport and secretion regulated by neurohumoral agents. In contrast, little is known about the pancreatic acinar cell in pathologic conditions such as pancreatitis and pancreatic cancer. We have preliminary data showing that the key agonist for pancreatic acinar cells, the hormone cholecystokinin (CCK), causes activation of intracellular signals (i.e. transcription factors and kinases) that regulate the production of proinflammatory cytokines and chemokines. We also have preliminary data showing that the pancreatic

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acinar cell responds to cytokines such as tumor necrosis factor (TNF-alpha) and that this agent modifies the effect of CCK on the intracellular signals in the pancreatic acinar cell that mediate the generation of the inflammatory molecules (cytokines, adhesion molecules, etc.). For the present application, we hypothesize that in the pancreatic acinar cell CCK activates intracellular signals modulated by TNF-alpha that mediate the expression of the inflammatory molecules and pancreatitis. The specific objectives for the present application are: (1). Determine the effects of CCK and TNF-alpha alone and in combination on activation and composition of the transcription factors, NF-kappa-B and AP-1, in pancreatic acinar cells in vitro. (2). Determine the intracellular signaling systems involved in mediating the effects of CCK and TNF-alpha on transcription factor activation. (3). Determine the effect of TNF-alpha on CCK-induced expression of cytokines in pancreatic acinar cells. (4). Determine the roles of specific NF-kappa-B proteins (i.e. p65, p50 and c-Rel) in regulating cytokine expression in pancreatic acinar cells in vitro. (5). Determine the roles of the specific NF-kappa-B proteins in regulating pancreatic cytokine expression and the inflammatory and cell death responses of experimental pancreatitis. In vitro experiments in this application will use acinar cells prepared by collagenase digestion of pancreas from rat or mouse. In vivo experiments will use mice with genetic deletions of various NF-kappa-B proteins as well as wild-type controls. Cytokines will be assayed using RT-PCR, Northern and Western blot analyses, and immunocytochemistry. Intracellular signals measured will include transcription factor activation, kinase activities, and second messengers measured with gel shift assay, Western blot analysis, enzyme assays, radioimmunoassay, and intracellular Ca2+ concentrations. Measures of pancreatitis will include both morphologic (including immunohistochemical) techniques and biochemical determinations of transcription factor activation, cytokine expression, and trypsin activation in the pancreatic tissue. The results of the experiments described in the present application will allow us to propose how CCK, together with a cytokine modulating its effects, acts on the pancreatic acinar cell to cause experimental pancreatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE PANINS OF PANCREATITIS,PANCREAS CANCER AND CONTROLS Principal Investigator & Institution: Goggins, Michael G.; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2003 Summary: Pancreatic cancer is the fifth leading cause of cancer death in the USA. Unfortunately, there is currently no effective screening test for asymptomatic disease and the vast majority of patients with pancreatic cancer present with advanced incurable disease. An effective method to detect early pancreatic cancers is urgently needed. This need is perhaps greatest in groups known to have an increased risk of developing pancreatic cancer. For example, patients with sporadic chronic pancreatitis have a lifetime risk of developing pancreatic cancer that approaches 4% and for patients with hereditary pancreatitis, the lifetime risk of pancreatic cancer is very high (approximately 50%). An improved understanding of early neoplasia in patients with chronic pancreatitis should form the foundation on which novel approaches to the early identification of invasive cancer could be developed. Several lines of evidence suggests that the precursor lesions of pancreatic carcinoma are the duct lesions known as pancreatic intraepithelial neoplasias (PanINs). First, PanINs are more common in pancreata with cancer than they were in pancreata without cancer. Second, PanINs found in pancreata with pancreatic cancer harbor many of the same genetic alterations

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as are found in pancreatic cancer such as activation of K-ras and inactivation of p16, DPC4, p53, and BRCA2. Third, several case studies report patients with PanINs progressing to invasive pancreatic cancer. Despite the risk of pancreatic cancer among patients with chronic pancreatitis, the genetic alterations in the PanINs from patients with chronic pancreatitis have not been well-studied. The aim of this study is to compare the frequency, timing and mechanism of several molecular events important for neoplastic progression in PanINs found in the setting of pancreatic cancer with PanINs found in the setting of chronic pancreatitis- associated and with PanINs from other benign pancreatic conditions. Specifically, using genetic, DNA methylation, and immunohistochemical techniques to compare the rates of a) genetic inactivation of DPC4 and b) genetic and epigenetic inactivation of p16 in 40 PanINs that arose in the setting of chronic pancreatitis 40 PanINs that arose in the setting of pancreatic cancer and 40 PanINs that arose in pancreata resected for benign pancreatic conditions without malignant potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSGENIC MOUSE MODELS OF PANCREATIC EXOCRINE FUNCTION Principal Investigator & Institution: Delisle, Robert C.; Associate Professor; Anatomy and Cell Biology; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: (provided by applicant): This grant application proposes to develop genetically engineered mouse models for acute pancreatitis and cystic fibrosis-related pancreatitis. We will focus on a recently discovered gene, which preliminary data suggest may play a role in development of pancreatitis, and also in the pathogenesis of cystic fibrosis (CF). The gene is called crpd in the mouse and dmbt1 in humans and it encodes the protein Muclin, a high molecular weight, and sulfated glycoprotein. This gene is most highly expressed in the exocrine pancreas, but also as different transcripts in other organs including the intestine, gallbladder, and kidney. The hypothesis is that Muclin is required for normal zymogen granule formation and subsequent solubilization of digestive enzymes upon exocytosis of the granules. We predict that if this gene is a disrupted zymogen granule will fail to mature creating a situation in the acinar cell where the zymogens will be prone to become activated, resulting in pancreatitis. The Muclin-deficient mouse model is intended to explore this hypothesis and, if this is borne out, it will make looking for mutations in this gene in human idiopathic pancreatitis a reasonable endeavor. We also predict that mice over expressing Muclin will exhibit poor release of zymogens after exocytosis and will be prone to CFlike plugging of the acinar lumen, which may predispose to pancreatitis. In CFTR-/mice, a model for CF, the pancreas exhibits over expression of Muclin, which is associated with protein, plugs in the acinar lumen. Mice with a Muclin transgene targeted to the pancreas will allow testing of this hypothesis. The specific aims are to produce genetically engineered mice: 1). Globally deficient in Muclin by targeting the first exon, which is present in all transcripts of this gene. 2). An exocrine cell-specific defective Muclin by targeting the last exon which is translated only in exocrine cell transcripts of the gene and codes for a transmembrane domain that may be important for Muclin' s exocrine function; 3). That over expresses Muclin in the pancreatic acinar cell using the rat elastase promoter to direct cell specific expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSPLANCENTAL PANCREATIC CARCINOGENESIS BY NNK Principal Investigator & Institution: Schuller, Hildegard M.; Distinguished Professor; Pathobiology; University of Tennessee Knoxville Knoxville, Tn 37996 Timing: Fiscal Year 2003; Project Start 01-SEP-1986; Project End 31-MAR-2007 Summary: (provided by applicant): The long-term goal of this project is to provide a basis for the development of novel intervention strategies for the most common type of pancreatic cancer, ductal adenocarcinoma. This cancer has a mortality of near 100% because diagnostic markers to identify the disease at an early stage are not available. We have combined the two risk factors for this cancer, smoking and drinking, by exposing hamsters in utero to the tobacco-carcinogen NNK and ethanol, resulting in the development of pancreatic ductal adenocarcinoma. Inhibitors of arachidonic acid (AA) metabolism reduced the pancreatic cancer incidence up to 50% while a beta-blocker reduced the cancer incidence to zero. In accord with these findings, the growth of cell lines derived from human pancreatic adenocarcinomas and immortalized normal human pancreatic duct epithelia were under beta-adrenergic control via the release of AA. Based on these novel findings, we propose three specific aims. Aim 1 will test the hypothesis that dietary n-3-polyunsaturated fatty acids (n-3-PUFAs) inhibit pancreatic carcinogenesis via reduction of tissue AA content and eicosanoid formation. This hypothesis will be tested in a bioassay in our hamster model, consisting of four dietary groups after completion of the tumor induction period (positive control, AA, n-3-PUFA, eicosapentaenoic acid EPA, AA+EPA). Pancreatic and liver tissues will be analyzed for fatty acids, AA-metabolites, AA-metabolizing enzymes and presence of pancreatic cancer. Data generated by this study will provide important information for dietary prevention of pancreatic cancer. Aim 2 will determine the downstream mitogenic signals activated by beta-adrenergic stimulation in cell lines from normal human pancreatic duct epithelia, pancreatic adenocarcinomas and will assess how these pathways are modulated by chronic exposure to NNK and ethanol. To achieve this goal, expression and activation levels of beta-adrenergic signaling components that have been described in other cell types will be assessed in the presence and absence of specific stimulators and inhibitors. Data generated will provide a basis for novel pharmacologic and molecular pancreatic cancer intervention strategies. Aim 3 will study the pathogenesis of pancreatic ductal adenocarcinoma in our hamster model by histopathology and identify early markers of the disease by molecular analysis of pancreatic duct cells, pancreatic islet cells and pancreatic acinar cells harvested at various stages during tumor development by laser capture microscopy. Data generated by these studies will help identify early markers of pancreatic cancer development that provide a basis for the early detection of this deadly malignancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRYPSIN, PAR-2 AND THE PAIN OF PANCREATITIS Principal Investigator & Institution: Pasricha, Pankaj J.; Chief; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 20-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The mechanism of pain in pancreatitis is poorly understood and its treatment remains difficult, in large part due to a lack of understanding of the underlying pathogenesis of nociceptor sensitization in this condition. Unlike that in other organs, inflammation in the pancreas is uniquely associated with a significant release of trypsin and other enzymes. Trypsin is an agonist of the protease activated receptor-2 (PAR-2), recently found to be expressed by

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nociceptor neurons and identified as a potentially key mediator of inflammatory hyperalgesia. In preliminary studies, using a specific PAR-2 activating peptide (AcPep), we found evidence of nociceptor sensitization in vitro in the form of enhanced capsaicin-and KC1-evoked release of CGRP, an important neuropeptide for nociceptive signaling. We then demonstrated that injection of AcPep into the pancreatic duct activated and sensitized pancreas-specific afferent neurons in vivo, as measured by spinal cord Fos expression. Further, we have shown that some of these effects can also be mimicked by activated trypsin. We therefore hypothesize that PAR-2 activation in the pancreas by trypsin activates and sensitizes the nociceptive response of this organ and contributes to the pain of pancreatitis. The overall goal of our studies is to characterize these effects further, using the following specific aims: 1) To study the effects of AcPep and trypsin on the pancreatic nociceptive response to painful stimuli and to determine if these are mediated by PAR-2. We will assess the response to intrapancreatic infusion of these PAR-2 agonists using in vivo behavioral and physiological assays of nociception in rats. The role of PAR-2 in mediating these effects will be tested by observing these responses, if any, in mice genetically engineered to lack PAR-2. 2) To study the effects of AcPep and trypsin on neurotransmitter release by primary afferent nociceptors and to determine if these are mediated by PAR-2. The effects of PAR-2 agonists on evoked CGRP release by cultured primary afferent neurons will be assessed and the role of PAR-2 in mediating these effects determined by performing similar studies on cultured neurons from PAR-2 knockout mice. 3) To determine the contribution PAR-2 to the overall nociceptive response in pancreatitis. The contribution of PAR-2 to pain in an experimental model of pancreatitis will be determined by behavioral, physiologic (spinal Fos expression) and neurotransmitter release studies in PAR-2 knockout mice. These studies will provide insight into the underlying mechanism of pancreatic pain that may eventually lead to new and more effective forms of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VACCINIA VIRUS VACCINE FOR TYPE 1 DIABETES Principal Investigator & Institution: Langridge, William H.; Biochemistry; Loma Linda University Loma Linda, Ca 92350 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Type 1 diabetes is a Thl lymphocyte mediated autoimmune disease that is partially suppressed by oral administration of small amounts of insulin or other diabetes autoantigens. To strengthen this promising immunotolerization approach to diabetes prevention, new innovative strategies are needed. In response to RFA-DK-02-023, we propose to determine the feasibility of a recombinant vaccinia virus (rVV) mediated autoantigen delivery system for suppression of Type 1 diabetes. Genes encoding proinsulin (INS) and glutamate decarboxylase (GAD) autoantigens fused to a cholera toxin B subunit (CTB) receptor IJgand in an rVV expression vector will be expressed in intestinal epithelial cells inoculated with rVV. Following enterocyte apoptosis, autoantigen fusion proteins will be taken up by APCs of the subepithelium or released into the gut and targeted via the CTB ligand to intestinal M cells for indirect APC processing. Two specific aims will determine (1) rVV MOl's required to generate optimum autoantigen protein synthesis in enterocyte cells in culture. (2) The efficacy of rVV mediated tolerance for prevention of Type1 diabetes in vivo and the nature of the T cell response underlying diabetes prevention. Prediabetic NOD/LtJ mice will be orally inoculated with rVV encoding CTB-INS and CTB-GAD enterocyte targeted autoantigen fusion proteins to generate maximum levels of protection from diabetes as measured by levels of insulitis and hyperglycemia.

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Mechanisms of immunity underlying vaccinia mediated autoantigen suppression of diabetes will be investigated by measurement of T lymphocyte responses to mucosal immunization measured by ELISA quantification of IL-10, TGF-beta, IL-2 and IFNgamma cytokines secreted from salivary gland, spleen, pancreas and mesenteric lymphoid cells. CTL and T lymphocyte proliferation in response to vaccina mediated synthesis of INS and GAD will be quantified by flow cytometric analysis of spleen and mesenteric lymph node memory CD4+ and CD8+ lymphocytes. Specific CTL responses to vaccinia infection will be quantified by LDH assays for rVV, CTB, INS and GAD proteins. The results of these experiments will increase our understanding of the immunological mechanisms underlying vaccinia virus mediated immunotolerization against Type 1 diabetes for the long term goal of generating safer, more effective and inexpensive mucosal vaccines for protection against this devastating form of diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VESICLE TRAFFICKING AND PANCREATIC ACINAR CELL SECRETION Principal Investigator & Institution: Mc Niven, Mark A.; Professor and Chair; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-APR-2005 Summary: The objective of this proposal is to define the molecular mechanisms involved in both normal and abnormal pancreatic enzyme secretion. Our focus is on the pancreatic acinar cell and the mechanisms that support the agonist-induced formation and transport of zymogen granules from the trans-Golgi network (TGN) to the apical membrane for subsequent enzyme release. Using both primary acini preparations and a novel cultured pancreatic acinar cell model that we developed, we have made the following novel observations. (i), CCK-stimulation induces vesiculation of the Golgi apparatus while increasing zymogen granule transport, (ii), specific vesicle-coat and cytoskeletal proteins are recruited to the acinar cell TGN following agonist stimulation, and (iii), the microtubule (Mt) associated motor enzyme kinesin is associated with zymogen granules and, along with Mts, is required for granule movement. This study will utilize state-of-the-art microscopic imaging techniques of living and fixed acinar cells expressing GFP-protein constructs, combined with biochemical and molecular methods to test the following CENTRAL HYPOTHESIS: specific coat and motor proteins in the acinar cell are recruited and activated during a secretory stimulus to mediate the appropriate formation and transport of zymogen granules from the TGN to the apical lumen. We predict that disruption of this zymogen transport machinery will lead to missorting of nascent proteases in the acinar cell and subsequent pancreatitis. Thus, we propose three SPECIFIC AIMS. First, we will define the structure of the acinar cell TGN and observe how it changes during stimulated secretion. Mechanistic studies will be conducted to inhibit motor and coat function and subsequently assess the effects on TGN structure and zymogen granule formation. Second, we will define which motor proteins support the transport of zymogen granules to the apical lumen and test whether these motors are upregulated during secretion. Third, we will directly test if a disruption of coat and motor proteins, or suprastimulation, leads to an aberrant missorting and subsequent release of zymogens into the cytoplasm. To our knowledge this will be one of the first studies to manipulate and view vesicle formation and transport in living acinar cells as they secrete. We are confident that this study will make important contributions essential to understanding pancreatic acinar cell function and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIDEOSCOPIC COLLECTIONS

DRAINAGE

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Principal Investigator & Institution: Horvath, Karen D.; Surgery; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): External drainage and antibiotics are the fundamental principles of treatment for infected pancreatic fluid collections following necrotizing pancreatitis. Without proper therapy, nearly all patients will die. Open surgical necrosectomy, or the process of removing necrotic tissue, is currently the standard of care. While highly effective, the large abdominal incision is associated with significant morbidity. Percutaneous catheter drainage is another type of external drainage with variable success rates. Although minimally invasive, the necrosectum often contains particulate debris, 10-30mm in size, which are poorly drained via the 410mm catheters. When percutaneous drainage fails, all patients crossover to open surgical necrosectomy. Preliminary data suggest that videoscopic-assisted retroperitoneal debridement (VARD) is a promising new method that combines the benefits of open surgical necrosectomy and percutaneous catheter drainage. Debridement occurs under direct vision through a small flank incision with videoscopic assistance. This project is a multicenter, single-arm, Phase II safety and efficacy study of patients undergoing VARD of infected pancreatic fluid collections. Patients enrolled will be limited to hemodynamically stable patients with documented infected pancreatic necrosis or pancreatic abscess as defined by the Atlanta Symposium. Patients will be strictly classified based on: CT classification, time from onset of pancreatitis to external drainage, and patient disease severity. Five major teaching hospitals will enroll 40 patients over 18 months. All patients will be followed for 6 months from the onset of pancreatitis. Safety issues will be monitored by an External Review Board. The hypothesis is: In patients with infected pancreatic fluid collections following acute pancreatitis, VARD provides a safe and efficacious procedure for draining infected pancreatic fluid collections adequately without need for crossover to open surgical necrosectomy. The specific aims are to assess: 1) safety and efficacy of VARD of infected pancreatic fluid collections; and 2) the clinical and functional outcomes of patients treated with VARD. The long-term goal is to use data obtained from this study as the basis for a multicenter, Phase III, randomized study comparing the VARD to the current standard of care, open surgical necrosectomy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, 3 4

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

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

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and type “pancreatitis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for pancreatitis in the PubMed Central database: •

Activation of polyamine catabolism in transgenic rats induces acute pancreatitis. by Alhonen L, Parkkinen JJ, Keinanen T, Sinervirta R, Herzig KH, Janne J.; 2000 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26940

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Calcium signaling and acute pancreatitis: Specific response to a promiscuous messenger. by Parekh AB.; 2000 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34065

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Differential recruitment of B and T cells in coxsackievirus B4-induced pancreatitis is influenced by a capsid protein. by Ramsingh AI, Lee WT, Collins DN, Armstrong LE.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192333

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Isolation of a novel Helicobacter species, Helicobacter cholecystus sp. nov., from the gallbladders of Syrian hamsters with cholangiofibrosis and centrilobular pancreatitis. by Franklin CL, Beckwith CS, Livingston RS, Riley LK, Gibson SV, Besch-Williford CL, Hook RR Jr.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229440

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Molecular phylogeny and in situ detection of the etiologic agent of necrotizing hepatopancreatitis in shrimp. by Loy JK, Dewhirst FE, Weber W, Frelier PF, Garbar TL, Tasca SI, Templeton JW.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168141

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Pancreatitis associated with hydroxyurea in combination with didanosine. by Longhurst HJ, Pinching AJ.; 2001 Jan 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26596

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Protection from Lethal Coxsackievirus-Induced Pancreatitis by Expression of Gamma Interferon. by Horwitz MS, Krahl T, Fine C, Lee J, Sarvetnick N.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104414

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Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. by Bhatia M, Saluja AK, Hofbauer B, Frossard JL, Lee HS, Castagliuolo I, Wang CC, Gerard N, Pothoulakis C, Steer ML.; 1998 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22564

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The course of traumatic pancreatitis in a patient with pancreas divisum: a case report. by Chryssou EG, Prassopoulos P, Mouzas J, Maris TG, Gourtsoyiannis N.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153522

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 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text

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

A case of autoimmune pancreatitis complicated with immune thrombocytopenia during maintenance therapy with prednisolone. Author(s): Nakamura A, Funatomi H, Katagiri A, Katayose K, Kitamura K, Seki T, Yamamura F, Aoyagi Y, Nishida H, Mitamura K. Source: Digestive Diseases and Sciences. 2003 October; 48(10): 1968-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627342&dopt=Abstract

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A case of autoimmune pancreatitis with initially negative autoantibodies turning positive during the clinical course. Author(s): Egawa N, Irie T, Tu Y, Kamisawa T. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1705-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560987&dopt=Abstract

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A case of tacrolimus (FK506)-induced pancreatitis and fatality 2 years postcadaveric renal transplant. Author(s): Ogunseinde BA, Wimmers E, Washington B, Iyob M, Cropper T, Callender CO. Source: Transplantation. 2003 July 27; 76(2): 448. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883222&dopt=Abstract

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Acquired factor VIII haemophilia in a patient with acute necrotic pancreatitis. Author(s): Kraemer DM, Kraus MR. Source: Journal of Internal Medicine. 2003 September; 254(3): 301-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930241&dopt=Abstract

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Acute biliary pancreatitis: when should the endoscopist intervene? Author(s): Fogel EL, Sherman S. Source: Gastroenterology. 2003 July; 125(1): 229-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851886&dopt=Abstract

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

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Acute pancreatitis after a course of clarithromycin. Author(s): Schouwenberg BJ, Deinum J. Source: The Netherlands Journal of Medicine. 2003 July; 61(7): 266-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567525&dopt=Abstract

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Acute pancreatitis after long-term therapy with mesalazine, and hyperamylasaemia associated with azathioprine in a patient with ulcerative colitis. Author(s): Toubanakis C, Batziou E, Sipsas N, Galanopoulos G, Tzivras M, Archimandritis A. Source: European Journal of Gastroenterology & Hepatology. 2003 August; 15(8): 933-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867808&dopt=Abstract

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Acute pancreatitis in childhood: analysis of literature data. Author(s): Benifla M, Weizman Z. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 169-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869890&dopt=Abstract

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Acute pancreatitis induced by diffuse pancreatic invasion of adult T-cell leukemia/lymphoma cells. Author(s): Mori A, Kikuchi Y, Motoori S, Watanabe J, Shinozaki M, Eguchi M. Source: Digestive Diseases and Sciences. 2003 October; 48(10): 1979-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627344&dopt=Abstract

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Acute pancreatitis presenting as a case of splenic rupture. Author(s): Adelekan MO, Nasmyth DG, Joglekar VM. Source: Hosp Med. 2003 July; 64(7): 432-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886858&dopt=Abstract

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Acute pancreatitis: an obscure complication of organophosphate intoxication. Author(s): Harputluoglu MM, Kantarceken B, Karincaoglu M, Aladag M, Yildiz R, Ates M, Yildirim B, Hilmioglu F. Source: Human & Experimental Toxicology. 2003 June; 22(6): 341-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856957&dopt=Abstract

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Alcoholic, but not biliary, pancreatitis varies seasonally in occurrence. Author(s): Raty S, Sand J, Alho H, Nordback I. Source: Scandinavian Journal of Gastroenterology. 2003 July; 38(7): 794-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889568&dopt=Abstract

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Alstrom syndrome with acute pancreatitis: a case report. Author(s): Wu WC, Chen SC, Dia CY, Yu ML, Hsieh MY, Lin ZY, Wang LY, Tsai JF, Chang WY, Chuang WL. Source: Kaohsiung J Med Sci. 2003 July; 19(7): 358-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926522&dopt=Abstract

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Angiographic features in acute pancreatitis: the severity of abdominal vessel ischemic change reflects the severity of acute pancreatitis. Author(s): Inoue K, Hirota M, Beppu T, Ishiko T, Kimura Y, Maeda K, Ogawa M. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 November; 4(6): 207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614201&dopt=Abstract

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Association between ACE inhibitors and acute pancreatitis in the elderly. Author(s): Cheng RM, Mamdani M, Jackevicius CA, Tu K. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 994-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841806&dopt=Abstract

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Association of keratin 8 gene mutation with chronic pancreatitis. Author(s): Cavestro GM, Frulloni L, Nouvenne A, Neri TM, Calore B, Ferri B, Bovo P, Okolicsanyi L, Di Mario F, Cavallini G. Source: Dig Liver Dis. 2003 June; 35(6): 416-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868678&dopt=Abstract

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Association of two polymorphisms of tumor necrosis factor gene with acute severe pancreatitis. Author(s): Zhang D, Li J, Jiang ZW, Yu B, Tang X. Source: The Journal of Surgical Research. 2003 June 15; 112(2): 138-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888330&dopt=Abstract

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Autoimmune pancreatitis and multiple bile duct strictures treated effectively with steroid. Author(s): Kojima E, Kimura K, Noda Y, Kobayashi G, Itoh K, Fujita N. Source: Journal of Gastroenterology. 2003; 38(6): 603-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856677&dopt=Abstract

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Autoimmune pancreatitis associated with idiopathic retroperitoneal fibrosis. Author(s): Fukukura Y, Fujiyoshi F, Nakamura F, Hamada H, Nakajo M. Source: Ajr. American Journal of Roentgenology. 2003 October; 181(4): 993-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500215&dopt=Abstract

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Autoimmune pancreatitis detected as a mass in the head of the pancreas without hypergammaglobulinemia, which relapsed after surgery: case report and review of the literature. Author(s): Taniguchi T, Tanio H, Seko S, Nishida O, Inoue F, Okamoto M, Ishigami S, Kobayashi H. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1465-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924637&dopt=Abstract

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Balthazar computed tomography severity index is superior to Ranson criteria and APACHE II and III scoring systems in predicting acute pancreatitis outcome. Author(s): Chatzicostas C, Roussomoustakaki M, Vardas E, Romanos J, Kouroumalis EA. Source: Journal of Clinical Gastroenterology. 2003 March; 36(3): 253-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590238&dopt=Abstract

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Bedside scoring system to predict the risk of developing pancreatitis following ERCP. Author(s): Friedland S, Soetikno RM, Vandervoort J, Montes H, Tham T, Carr-Locke DL. Source: Endoscopy. 2002 June; 34(6): 483-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048633&dopt=Abstract

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Benefit of continuous regional arterial infusion of protease inhibitor and antibiotic in the management of acute necrotizing pancreatitis. Author(s): Takeda K, Yamauchi J, Shibuya K, Sunamura M, Mikami Y, Matsuno S. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(6): 668-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120252&dopt=Abstract

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Bile duct involvement in a case of autoimmune pancreatitis successfully treated with an oral steroid. Author(s): Kuroiwa T, Suda T, Takahashi T, Hirono H, Natsui M, Motoyama H, Nomoto M, Aoyagi Y. Source: Digestive Diseases and Sciences. 2002 August; 47(8): 1810-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184534&dopt=Abstract

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Biliary ascariasis with acute hemorrhagic pancreatitis: a case report. Author(s): Cirstose GC, Baraki A. Source: Ethiop Med J. 1999 April; 37(2): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965640&dopt=Abstract

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Biliary emergencies: pancreatitis, cholangitis, and more. Author(s): Mitchell RM, Byrne MF. Source: Semin Gastrointest Dis. 2003 April; 14(2): 77-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889582&dopt=Abstract

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Biliary pancreatitis. Author(s): Carr-Locke DL. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 March; 17(3): 205-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677272&dopt=Abstract

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Blue toe syndrome: a rare complication of acute pancreatitis. Author(s): Bhalla A, Gupta S, Jain AP, Jajoo UN, Gupta OP, Kalantri SP. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 January; 4(1): 17-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555011&dopt=Abstract

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Body composition, physiological function and psychological changes in patients with predicted severe acute pancreatitis. Author(s): Gupta R, Rajani R, Primrose JN, Johnson CD. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120269&dopt=Abstract

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Can roxithromycin and betamethasone induce acute pancreatitis? A case report. Author(s): Renkes P, Petitpain N, Cosserat F, Bangratz S, Trechot P. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 September; 4(5): 184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526130&dopt=Abstract

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Cerebral fat embolism as a rare possible complication of traumatic pancreatitis. Author(s): Bhalla A, Sachdev A, Lehl SS, Singh R, D'Cruz S. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 July; 4(4): 155-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853683&dopt=Abstract

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CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients. Author(s): Bernardino AL, Guarita DR, Mott CB, Pedroso MR, Machado MC, Laudanna AA, Tani CM, Almeida FL, Zatz M. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 September; 4(5): 169-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526128&dopt=Abstract

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Cholangitis score: a scoring system to predict severe cholangitis in gallstone pancreatitis. Author(s): Isogai M, Yamaguchi A, Harada T, Kaneoka Y, Suzuki M. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2002; 9(1): 98-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021903&dopt=Abstract

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Chromosomal instability in pancreatic ductal cells from patients with chronic pancreatitis and pancreatic adenocarcinoma. Author(s): Moskovitz AH, Linford NJ, Brentnall TA, Bronner MP, Storer BE, Potter JD, Bell RH Jr, Rabinovitch PS. Source: Genes, Chromosomes & Cancer. 2003 June; 37(2): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696069&dopt=Abstract

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Chronic pancreatitis. Author(s): Tsirambidis JV, Conwell DL, Zuccaro G. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2003 January 9; 5(1): 17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827078&dopt=Abstract

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Chronic pancreatitis: the perspective of pain generation by neuroimmune interaction. Author(s): Di Sebastiano P, di Mola FF, Bockman DE, Friess H, Buchler MW. Source: Gut. 2003 June; 52(6): 907-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740353&dopt=Abstract

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Clinical effects of continuous high volume hemofiltration on severe acute pancreatitis complicated with multiple organ dysfunction syndrome. Author(s): Wang H, Li WQ, Zhou W, Li N, Li JS. Source: World Journal of Gastroenterology : Wjg. 2003 September; 9(9): 2096-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970914&dopt=Abstract

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Clinical evidence of pathogenesis in chronic pancreatitis. Author(s): Hayakawa T, Naruse S, Kitagawa M, Ishiguro H, Jin CX, Kondo T. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2002; 9(6): 669-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658399&dopt=Abstract

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Clinical study on nutrition support in patients with severe acute pancreatitis. Author(s): Zhao G, Wang CY, Wang F, Xiong JX. Source: World Journal of Gastroenterology : Wjg. 2003 September; 9(9): 2105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970916&dopt=Abstract

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Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Author(s): Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K, Egawa N, Nakajima H. Source: Gut. 2003 May; 52(5): 683-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692053&dopt=Abstract

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Colonic involvement in non-necrotizing acute pancreatitis: correlation of CT findings with the clinical course of affected patients. Author(s): Wiesner W, Studler U, Kocher T, Degen L, Buitrago-Tellez CH, Steinbrich W. Source: European Radiology. 2003 April; 13(4): 897-902. Epub 2002 June 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664132&dopt=Abstract

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COMP is selectively up-regulated in degenerating acinar cells in chronic pancreatitis and in chronic-pancreatitis-like lesions in pancreatic cancer. Author(s): Liao Q, Kleeff J, Xiao Y, Di Cesare PE, Korc M, Zimmermann A, Buchler MW, Friess H. Source: Scandinavian Journal of Gastroenterology. 2003 February; 38(2): 207-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678339&dopt=Abstract

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Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis. Author(s): Masci E, Cavallini G, Mariani A, Frulloni L, Testoni PA, Curioni S, Tittobello A, Uomo G, Costamagna G, Zambelli S, Macarri G, Innocenti P, Dragonetti C; Gabexate in Digestive Endoscopy-Italian Group II. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2182-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14572565&dopt=Abstract

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Compartmentalization of the inflammatory response during acute pancreatitis: correlation with local and systemic complications. Author(s): Dugernier TL, Laterre PF, Wittebole X, Roeseler J, Latinne D, Reynaert MS, Pugin J. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 15; 168(2): 148-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851244&dopt=Abstract

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Compartments that cause the real damage in severe acute pancreatitis. Author(s): Neoptolemos JP. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 15; 168(2): 141-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851239&dopt=Abstract

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Continuous veno venous hemofiltration in treatment of acute necrotizing pancreatitis. Author(s): Xie H, Ji D, Gong D, Liu Y, Xu B, Zhou H, Liu Z, Li L, Li W, Quan Z, Li J. Source: Chinese Medical Journal. 2003 April; 116(4): 549-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875720&dopt=Abstract

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Corticosteroid-responsive diabetes mellitus associated with autoimmune pancreatitis: pathological examinations of the endocrine and exocrine pancreas. Author(s): Tanaka S, Kobayashi T, Nakanishi K, Okubo M, Odawara M, Murase T, Hashimoto M, Watanabe G, Matsushita H, Inoko H, Takeuchi K. Source: Annals of the New York Academy of Sciences. 2002 April; 958: 152-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021096&dopt=Abstract

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Current aspects of the pathophysiology of acute pancreatitis and therapeutic effects of an inflammatory cell infiltration inhibitor. Author(s): Manabe T. Source: Journal of Gastroenterology. 2003; 38(3): 305-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693385&dopt=Abstract

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Cystic fibrosis, pregnancy, and recurrent, acute pancreatitis. Author(s): Virgilis D, Rivkin L, Samueloff A, Picard E, Goldberg S, Faber J, Kerem E, Wilschanski M. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 April; 36(4): 486-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658041&dopt=Abstract

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Decreased HLA (human leucocyte antigen)-DR expression on peripheral blood monocytes predicts the development of organ failure in patients with acute pancreatitis. Author(s): Mentula P, Kylanpaa-Back ML, Kemppainen E, Takala A, Jansson SE, Kautiainen H, Puolakkainen P, Haapiainen R, Repo H. Source: Clinical Science (London, England : 1979). 2003 October; 105(4): 409-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780344&dopt=Abstract

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Decreasing the plasma triglyceride level in hypertriglyceridemia-induced pancreatitis in pregnancy: a case report. Author(s): Loo CC, Tan JY. Source: American Journal of Obstetrics and Gynecology. 2002 July; 187(1): 241-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114919&dopt=Abstract

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Dehydration and pancreatitis in a child lost in the mountains for 2 days. Author(s): Kizer KW. Source: Wilderness Environ Med. 1995 August; 6(3): 304-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990095&dopt=Abstract

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Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas. Author(s): Evans JD, Cornford PA, Dodson A, Greenhalf W, Foster CS, Neoptolemos JP. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(3): 254-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120204&dopt=Abstract

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Development and use of a new staging system for severe acute pancreatitis based on a nationwide survey in Japan. Author(s): Ogawa M, Hirota M, Hayakawa T, Matsuno S, Watanabe S, Atomi Y, Otsuki M, Kashima K, Koizumi M, Harada H, Yamamoto M, Nishimori I. Source: Pancreas. 2002 November; 25(4): 325-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409824&dopt=Abstract

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Diabetic hypertriglyceridemia-induced acute pancreatitis masquerading as biliary pancreatitis. Author(s): Huang DB, Raskin P. Source: Journal of Diabetes and Its Complications. 2002 March-April; 16(2): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12039403&dopt=Abstract

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Diabetic ketoacidosis and persistent hyperglycemia as long-term complications of Lasparaginase-induced pancreatitis. Author(s): Hsu YJ, Chen YC, Ho CL, Kao WY, Chao TY. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 September; 65(9): 441-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433031&dopt=Abstract

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Diagnosis and early management of acute pancreatitis. Author(s): Powell JJ, Parks RW. Source: Hosp Med. 2003 March; 64(3): 150-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669481&dopt=Abstract

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Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Author(s): Murray B, Carter R, Imrie C, Evans S, O'Suilleabhain C. Source: Gastroenterology. 2003 June; 124(7): 1786-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806612&dopt=Abstract

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Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA. Author(s): Maire F, Micard S, Hammel P, Voitot H, Levy P, Cugnenc PH, Ruszniewski P, Puig PL. Source: British Journal of Cancer. 2002 August 27; 87(5): 551-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189555&dopt=Abstract

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Direct retroperitoneal open drainage via a long posterior oblique incision for infected necrotizing pancreatitis: report of three cases. Author(s): Morise Z, Yamafuji K, Asami A, Takeshima K, Hayashi N, Endo T, Hattori T, Ito Y, Tokura Y. Source: Surgery Today. 2003; 33(4): 315-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707833&dopt=Abstract

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Discrepancies between population-based data and adverse reaction reports in assessing drugs as causes of acute pancreatitis. Author(s): Lancashire RJ, Cheng K, Langman MJ. Source: Alimentary Pharmacology & Therapeutics. 2003 April 1; 17(7): 887-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656691&dopt=Abstract

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Discussion on genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis. Author(s): Dray X, Marteau P, Bienvenu T, Dusser D, Hubert D. Source: Gastroenterology. 2003 October; 125(4): 1286. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552321&dopt=Abstract

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Distribution of Indian hedgehog and its receptors patched and smoothened in human chronic pancreatitis. Author(s): Kayed H, Kleeff J, Keleg S, Buchler MW, Friess H. Source: The Journal of Endocrinology. 2003 September; 178(3): 467-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967338&dopt=Abstract

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Does a lack of reactivity to alpha-fodrin indicate the existence of primary autoimmune pancreatitis? Author(s): Horiuchi A, Kawa S, Hamano H, Hayashi Y, Kiyosawa K. Source: The American Journal of Gastroenterology. 2002 May; 97(5): 1275-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014754&dopt=Abstract

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Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study. Author(s): Fazel A, Quadri A, Catalano MF, Meyerson SM, Geenen JE. Source: Gastrointestinal Endoscopy. 2003 March; 57(3): 291-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612504&dopt=Abstract

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Does prophylactic administration of corticosteroid reduce the risk and severity of post-ERCP pancreatitis: a randomized, prospective, multicenter study. Author(s): Sherman S, Blaut U, Watkins JL, Barnett J, Freeman M, Geenen J, Ryan M, Parker H, Frakes JT, Fogel EL, Silverman WB, Dua KS, Aliperti G, Yakshe P, Uzer M, Jones W, Goff J, Earle D, Temkit M, Lehman GA. Source: Gastrointestinal Endoscopy. 2003 July; 58(1): 23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838216&dopt=Abstract

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Duct drainage alone is sufficient in the operative management of pancreatic pseudocyst in patients with chronic pancreatitis. Author(s): Nealon WH, Walser E. Source: Annals of Surgery. 2003 May; 237(5): 614-20; Discussion 620-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724627&dopt=Abstract

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Duodenal air dissection secondary to intramural hematoma in necrotizing pancreatitis. Author(s): Dugernier TL, Breuskin FM. Source: Endoscopy. 2002 December; 34(12): 1024. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471553&dopt=Abstract

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Duodenal ulcer and pancreatitis associated with pancreatic arteriovenous malformation. Author(s): Aida K, Nakamura H, Kihara Y, Abe S, Okamoto K, Otsuki M. Source: European Journal of Gastroenterology & Hepatology. 2002 May; 14(5): 551-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984154&dopt=Abstract

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Early activation of peripheral lymphocytes in human acute pancreatitis. Author(s): Pezzilli R, Maldini M, Morselli-Labate AM, Barakat B, Romboli E, Beltrandi E, Migliori M, Tomassetti P, Corinaldesi R. Source: Journal of Clinical Gastroenterology. 2003 April; 36(4): 360-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642746&dopt=Abstract

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Early assessment of severity in acute pancreatitis. Author(s): Taxonera Samso C. Source: Rev Esp Enferm Dig. 2002 September; 94(9): 515-22. English, Spanish. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587231&dopt=Abstract

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Early measurement of procalcitonin does not predict severity in patients with acute pancreatitis. Author(s): Frasquet J, Saez J, Trigo C, Martinez J, Such J, Perez-Mateo M. Source: The British Journal of Surgery. 2003 September; 90(9): 1129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945081&dopt=Abstract

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Early multi-system organ failure associated with acute pancreatitis: a plea for a conservative therapeutic strategy. Author(s): Dugernier T, Reynaert M, Laterre PF. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 177-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891929&dopt=Abstract

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Early onset idiopathic chronic pancreatitis: Is there a role for endoscopic treatment? Author(s): Gabbrielli A. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 July; 4(4): 133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853680&dopt=Abstract

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Early prediction of early pancreatitis. Author(s): Losanoff JE, Richman BW, Jones JW. Source: World Journal of Surgery. 2003 April; 27(4): 498; Author Reply 498-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658503&dopt=Abstract

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Early preventive treatment for severe acute pancreatitis combined with lung injury. Author(s): Liu X, Liu Q, Pan C. Source: Chinese Journal of Traumatology = Chung-Hua Ch'uang Shang Tsa Chih / Chinese Medical Association. 2002 June; 5(3): 190-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034086&dopt=Abstract

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Early severity indexes in acute pancreatitis. Author(s): Johnson CD. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 174-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891928&dopt=Abstract

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Elevated fasting plasma level of islet amyloid polypeptide (IAPP) in chronic alcoholic pancreatitis (CAP). Author(s): Gasiorowska A, Orszulak-Michalak D, Kozlowska A, Malecka-Panas E. Source: Hepatogastroenterology. 2003 January-February; 50(49): 258-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630035&dopt=Abstract

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Emerging concepts for the mechanism of alcoholic pancreatitis from experimental models. Author(s): Pandol SJ, Gukovsky I, Satoh A, Lugea A, Gukovskaya AS. Source: Journal of Gastroenterology. 2003; 38(7): 623-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898353&dopt=Abstract

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Enalapril-induced acute recurrent pancreatitis. Author(s): Carnovale A, Esposito P, Bassano P, Russo L, Uomo G. Source: Dig Liver Dis. 2003 January; 35(1): 55-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725609&dopt=Abstract

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Endoscopic pancreaticoduodenostomy for treatment of pancreatic duct disconnection because of severe acute pancreatitis. Author(s): Zein CO, Baron TH, Morgan DE. Source: Gastrointestinal Endoscopy. 2003 July; 58(1): 130-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838241&dopt=Abstract

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Endoscopic stent therapy in advanced chronic pancreatitis: relationships between ductal changes, clinical response, and stent patency. Author(s): Morgan DE, Smith JK, Hawkins K, Wilcox CM. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 821-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738462&dopt=Abstract

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Endoscopic therapy of chronic pancreatitis. Author(s): Deviere J. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 184-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891930&dopt=Abstract

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Eosinophilic gastroenteritis causing pancreatitis and pancreaticobiliary ductal dilation. Author(s): Polyak S, Smith TA, Mertz H. Source: Digestive Diseases and Sciences. 2002 May; 47(5): 1091-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018905&dopt=Abstract

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Eosinophilic pancreatitis and increased eosinophils in the pancreas. Author(s): Abraham SC, Leach S, Yeo CJ, Cameron JL, Murakata LA, Boitnott JK, Albores-Saavedra J, Hruban RH. Source: The American Journal of Surgical Pathology. 2003 March; 27(3): 334-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604889&dopt=Abstract

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ERCP and acute pancreatitis. Author(s): Fiocca F, Santagati A, Ceci V, Donatelli G, Pasqualini MJ, Moretti MG, Speranza V, Di Giuli M, Minervini S, Sportelli G, Giri S. Source: Eur Rev Med Pharmacol Sci. 2002 January-February; 6(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608652&dopt=Abstract

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Evidence-based surgery in chronic pancreatitis. Author(s): Hartel M, Tempia-Caliera AA, Wente MN, Z'graggen K, Friess H, Buchler MW. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2003 April; 388(2): 132-9. Epub 2003 March 18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712343&dopt=Abstract

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Evolving concepts in the pathophysiology of acute pancreatitis. Author(s): Zyromski N, Murr MM. Source: Surgery. 2003 March; 133(3): 235-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660632&dopt=Abstract

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Expression patterns of protein kinase C isoenzymes are characteristically modulated in chronic pancreatitis and pancreatic cancer. Author(s): Evans JD, Cornford PA, Dodson A, Neoptolemos JP, Foster CS. Source: American Journal of Clinical Pathology. 2003 March; 119(3): 392-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645342&dopt=Abstract

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Factors predisposing to severe acute pancreatitis: evaluation and prevention. Author(s): Sun B, Li HL, Gao Y, Xu J, Jiang HC. Source: World Journal of Gastroenterology : Wjg. 2003 May; 9(5): 1102-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717866&dopt=Abstract

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Fatal acute pancreatitis. Characteristics of patients never reaching hospital. Author(s): Andersson R, Andren-Sandberg A. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2003; 3(1): 64-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649566&dopt=Abstract

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Fatal lactic acidosis and pancreatitis associated with ribavirin and didanosine therapy. Author(s): Butt AA. Source: Aids Read. 2003 July; 13(7): 344-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889452&dopt=Abstract

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Fatal outcome in acute pancreatitis: its occurrence and early prediction. Author(s): Blum T, Maisonneuve P, Lowenfels AB, Lankisch PG. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(3): 237-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120201&dopt=Abstract

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Fatal pancreatitis associated with valproic acid: review of the literature. Author(s): Yazdani K, Lippmann M, Gala I. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2002 July; 81(4): 305-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169885&dopt=Abstract

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Fatal splenic arterial aneurysmal rupture associated with chronic pancreatitis. Author(s): Lamba M, Veinot JP, Acharya V, Moyana T. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 2002 September; 23(3): 281-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198358&dopt=Abstract

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Fatty acid abnormalities in chronic pancreatitis: effect of concomitant diabetes mellitus. Author(s): Quilliot D, Walters E, Bohme P, Lacroix B, Bonte JP, Fruchart JC, Drouin P, Duriez P, Ziegler O. Source: European Journal of Clinical Nutrition. 2003 March; 57(3): 496-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627189&dopt=Abstract

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Fatty acid ethyl esters and ethanol-induced pancreatitis. Author(s): Kaphalia BS, Ansari GA. Source: Cell Mol Biol (Noisy-Le-Grand). 2001; 47 Online Pub: Ol173-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936865&dopt=Abstract

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Feasibility study using a new small electronic pancreatoscope: description of findings in chronic pancreatitis. Author(s): Kodama T, Imamura Y, Sato H, Koshitani T, Abe M, Kato K, Uehira H, Horii Y, Yamane Y, Kashima K, Yamagishi H. Source: Endoscopy. 2003 April; 35(4): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664386&dopt=Abstract

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Fecal elastase 1 measurement compared with endoscopic retrograde cholangiopancreatography for the diagnosis of chronic pancreatitis. Author(s): Hardt PD, Marzeion AM, Schnell-Kretschmer H, Wusten O, Nalop J, Zekorn T, Klor HU. Source: Pancreas. 2002 July; 25(1): E6-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131782&dopt=Abstract

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From acinar cell damage to systemic inflammatory response: current concepts in pancreatitis. Author(s): Weber CK, Adler G. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(4): 356-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120214&dopt=Abstract

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From acute to chronic pancreatitis: the role of mutations in the pancreatic secretory trypsin inhibitor gene. Author(s): Hirota M, Kuwata K, Ohmuraya M, Ogawa M. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 March; 4(2): 83-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629264&dopt=Abstract

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Fungal infections in patients with severe acute pancreatitis and the use of prophylactic therapy. Author(s): De Waele JJ, Vogelaers D, Blot S, Colardyn F. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 15; 37(2): 208-13. Epub 2003 Jul 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856213&dopt=Abstract

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Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial. Author(s): Andriulli A, Clemente R, Solmi L, Terruzzi V, Suriani R, Sigillito A, Leandro G, Leo P, De Maio G, Perri F. Source: Gastrointestinal Endoscopy. 2002 October; 56(4): 488-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297762&dopt=Abstract

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Gallbladder ascariasis in a patient with severe pancreatitis. Author(s): Miller G, Schecter WP, Harris HW. Source: Surgery. 2003 April; 133(4): 445-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717365&dopt=Abstract

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Gallium uptake in complicated pancreatitis. Author(s): Spieth ME, Gauger BS. Source: Ajr. American Journal of Roentgenology. 2003 April; 180(4): 1177; Author Reply 1177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646480&dopt=Abstract

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Gallstone pancreatitis: when is endoscopic retrograde cholangiopancreatography truly necessary? Author(s): Kraft M, Lerch MM. Source: Current Gastroenterology Reports. 2003 April; 5(2): 125-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631452&dopt=Abstract

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Gallstones, gallbladder disease, and pancreatitis: cross-sectional and 2-year data from the Swedish Obese Subjects (SOS) and SOS reference studies. Author(s): Torgerson JS, Lindroos AK, Naslund I, Peltonen M. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1032-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809825&dopt=Abstract

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Gastric colonisation, intestinal permeability and septic morbidity in acute pancreatitis. Author(s): McNaught CE, Woodcock NP, Mitchell CJ, Rowley G, Johnstone D, MacFie J. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2002; 2(5): 463-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378114&dopt=Abstract

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Gastrointestinal disorders of the critically ill. Shock and acute pancreatitis. Author(s): Isenmann R, Henne-Bruns D, Adler G. Source: Best Practice & Research. Clinical Gastroenterology. 2003 June; 17(3): 345-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763500&dopt=Abstract

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Gastrointestinal dysmotility in patients with acute pancreatitis. Author(s): Wang X, Gong Z, Wu K, Wang B, Yuang Y. Source: Journal of Gastroenterology and Hepatology. 2003 January; 18(1): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519225&dopt=Abstract

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Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin. Author(s): Descamps FJ, Van den Steen PE, Martens E, Ballaux F, Geboes K, Opdenakker G. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 May; 17(8): 887-9. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626433&dopt=Abstract

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Gene symbol: Spink1-Omim 167790. Disease: Hereditary pancreatitis. Author(s): Deybach JC, Phung L, Lamoril J, Bouizegarene P, Levy P, Deybach JC, Ruszniewski P. Source: Human Genetics. 2003 September; 113(4): 369. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974284&dopt=Abstract

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Genetic aspects of chronic pancreatitis, and the exploration of an association with keratin 8/18. Author(s): Drenth JP, Verlaan M. Source: Dig Liver Dis. 2003 June; 35(6): 386-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868673&dopt=Abstract

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Genetic basis of chronic pancreatitis. Author(s): Jansen JB, te Morsche R, van Goor H, Drenth JP. Source: Scandinavian Journal of Gastroenterology. Supplement. 2002; (236): 91-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408512&dopt=Abstract

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Genetic disorders in pancreatitis: Implications in the pathogenesis of acute and chronic pancreatitis. Author(s): Mossner J, Teich N. Source: Surgery. 2002 September; 132(3): 421-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324754&dopt=Abstract

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Genetic factors in pancreatitis. Author(s): Grendell JH. Source: Current Gastroenterology Reports. 2003 April; 5(2): 105-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631449&dopt=Abstract

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Genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis. Author(s): Durno C, Corey M, Zielenski J, Tullis E, Tsui LC, Durie P. Source: Gastroenterology. 2002 December; 123(6): 1857-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454843&dopt=Abstract

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Germline mutations in CFTR and PSTI genes in chronic pancreatitis patients. Author(s): Gaia E, Salacone P, Gallo M, Promis GG, Brusco A, Bancone C, Carlo A. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2416-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452372&dopt=Abstract

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Gestational hyperlipidaemic pancreatitis. Author(s): Choy CM, Tam WH, Leung TN. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 July; 109(7): 847-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135226&dopt=Abstract

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Giant splenic artery aneurysm associated with chronic pancreatitis. Author(s): Iki K, Tsunoda T. Source: Digestive Surgery. 2003; 20(1): 10-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637798&dopt=Abstract

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Groove pancreatitis: report of a case and review of the clinical and radiologic features of groove pancreatitis reported in Japan. Author(s): Shudo R, Yazaki Y, Sakurai S, Uenishi H, Yamada H, Sugawara K, Okamura M, Yamaguchi K, Terayama H, Yamamoto Y. Source: Intern Med. 2002 July; 41(7): 537-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132521&dopt=Abstract

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Gut barrier dysfunction in patients with acute pancreatitis. Author(s): Ammori BJ. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2002; 9(4): 411-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483261&dopt=Abstract

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Hepatic injury and pancreatitis during treatment with serotonin reuptake inhibitors: data from the World Health Organization (WHO) database of adverse drug reactions. Author(s): Spigset O, Hagg S, Bate A. Source: International Clinical Psychopharmacology. 2003 May; 18(3): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702895&dopt=Abstract

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Hereditary pancreatitis in Japan: a review of pancreatitis-associated gene mutations. Author(s): Nishimori I, Onishi S. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(5): 444-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120222&dopt=Abstract

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Hereditary pancreatitis in North America: the Pittsburgh-Midwest Multi-Center Pancreatic Study Group Study. Author(s): Applebaum-Shapiro SE, Finch R, Pfutzer RH, Hepp LA, Gates L, Amann S, Martin S, Ulrich CD 2nd, Whitcomb DC. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(5): 439-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120221&dopt=Abstract

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Hereditary pancreatitis. Author(s): Charnley RM. Source: World Journal of Gastroenterology : Wjg. 2003 January; 9(1): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508340&dopt=Abstract

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Hereditary pancreatitis: a model for understanding the genetic basis of acute and chronic pancreatitis. Author(s): Whitcomb DC. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(6): 565-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120237&dopt=Abstract

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Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-alpha) promoter region or the TNF receptor 1 (TNFR1) gene. Author(s): Schneider A, Pogue-Geile K, Barmada MM, Myers-Fong E, Thompson BS, Whitcomb DC. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2003 March-April; 5(2): 120-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644782&dopt=Abstract

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Herpes simplex pancreatitis. Author(s): Shintaku M, Umehara Y, Iwaisako K, Tahara M, Adachi Y. Source: Archives of Pathology & Laboratory Medicine. 2003 February; 127(2): 231-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562243&dopt=Abstract

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High signal peripancreatic fat on fat-suppressed spoiled gradient echo imaging in acute pancreatitis: preliminary evaluation of the prognostic significance. Author(s): Martin DR, Karabulut N, Yang M, McFadden DW. Source: Journal of Magnetic Resonance Imaging : Jmri. 2003 July; 18(1): 49-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815639&dopt=Abstract

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How far are we from the most accurate classification system for chronic pancreatitis ? Author(s): Uomo G. Source: Jop [electronic Resource] : Journal of the Pancreas. 2002 May; 3(3): 62-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004162&dopt=Abstract

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How hemolysis causes acute pancreatitis. Author(s): Saruc M, Ozden N, Yuceyar H. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 December; 8(12): Le51-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546022&dopt=Abstract

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How to think about SPINK and pancreatitis. Author(s): Whitcomb DC. Source: The American Journal of Gastroenterology. 2002 May; 97(5): 1085-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014708&dopt=Abstract

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How we do it: Acute pancreatitis. Author(s): Horton KM. Source: Critical Reviews in Computed Tomography. 2003; 44(2): 63-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757312&dopt=Abstract

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Human leukocyte antigen-DR expression on peripheral monocytes as a predictive marker of sepsis during acute pancreatitis. Author(s): Satoh A, Miura T, Satoh K, Masamune A, Yamagiwa T, Sakai Y, Shibuya K, Takeda K, Kaku M, Shimosegawa T. Source: Pancreas. 2002 October; 25(3): 245-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370535&dopt=Abstract

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Hyperlipemic pancreatitis and pseudocyst formation in late pregnancy. Author(s): Qin H, Goldstein L, Iwanicke S, Mackay E, Sutherland F. Source: Hepatogastroenterology. 2003 May-June; 50(51): 870-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828107&dopt=Abstract

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Hyperlipidemic pancreatitis during pregnancy. Author(s): Bildirici I, Esinler I, Deren O, Durukan T, Kabay B, Onderoglu L. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 May; 81(5): 468-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027823&dopt=Abstract

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Hypertriglyceridemia and pancreatitis associated with estramustine phosphate. Author(s): Olson EL, Whang YE. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 August; 25(4): 342-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151961&dopt=Abstract

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Hypertriglyceridemia, acute pancreatitis, and diabetic ketoacidosis possibly associated with mirtazapine therapy: a case report. Author(s): Chen JL, Spinowitz N, Karwa M. Source: Pharmacotherapy. 2003 July; 23(7): 940-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885107&dopt=Abstract

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Hypertriglyceridemia-induced acute pancreatitis--treatment with heparin and insulin. Author(s): Monga A, Arora A, Makkar RP, Gupta AK. Source: Indian J Gastroenterol. 2003 May-June; 22(3): 102-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839385&dopt=Abstract

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Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Author(s): Abou-Assi S, Craig K, O'Keefe SJ. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358242&dopt=Abstract

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Hypothermia and acute pancreatitis: myth or reality? Author(s): Stiff RE, Morris-Stiff GJ, Torkington J. Source: Journal of the Royal Society of Medicine. 2003 May; 96(5): 228-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724432&dopt=Abstract

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IAP guidelines in acute pancreatitis. Author(s): Sarr MG. Source: Digestive Surgery. 2003; 20(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846213&dopt=Abstract

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Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Author(s): Notohara K, Burgart LJ, Yadav D, Chari S, Smyrk TC. Source: The American Journal of Surgical Pathology. 2003 August; 27(8): 1119-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883244&dopt=Abstract

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Idiopathic pancreatitis may be associated with ulcerative colitis. Author(s): Okano A, Takakuwa H, Nishio A. Source: Intern Med. 2003 January; 42(1): 125-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583634&dopt=Abstract

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Idiopathic vs hereditary pancreatitis. Author(s): Chen JM, Ferec C. Source: Jama : the Journal of the American Medical Association. 2003 February 26; 289(8): 984-5; Author Reply 985. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597745&dopt=Abstract

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Idiopathic vs hereditary pancreatitis. Author(s): Keim V, Teich N. Source: Jama : the Journal of the American Medical Association. 2003 February 26; 289(8): 983-4; Author Reply 985. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597744&dopt=Abstract

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Imaging of acute pancreatitis. Author(s): Merkle EM, Gorich J. Source: European Radiology. 2002 August; 12(8): 1979-92. Epub 2002 February 02. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136316&dopt=Abstract

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Immune function in patients with acute pancreatitis. Author(s): Uehara S, Gothoh K, Handa H, Tomita H, Tomita Y. Source: Journal of Gastroenterology and Hepatology. 2003 April; 18(4): 363-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653883&dopt=Abstract

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Immunological findings in acute and chronic pancreatitis. Author(s): Bhatnagar A, Wig JD, Majumdar S. Source: Anz Journal of Surgery. 2003 January-February; 73(1-2): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534743&dopt=Abstract

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Incidence and management of biliary pancreatitis in cholecystectomized patients. Results of a 7-year study. Author(s): Gloor B, Stahel PF, Muller CA, Worni M, Buchler MW, Uhl W. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 March-April; 7(3): 372-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654562&dopt=Abstract

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Incidence, etiology, and impact of Fever in patients with acute pancreatitis. Author(s): Bohidar NP, Garg PK, Khanna S, Tandon RK. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2003; 3(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649559&dopt=Abstract

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Increased nitric oxide excretion in patients with severe acute pancreatitis: evidence of an endotoxin mediated inflammatory response? Author(s): Rahman SH, Ammori BJ, Larvin M, McMahon MJ. Source: Gut. 2003 February; 52(2): 270-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524412&dopt=Abstract

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Infected necrosis complicating acute pancreatitis: experience with 131 cases. Author(s): Bhansali SK, Shah SC, Desai SB, Sunawala JD. Source: Indian J Gastroenterol. 2003 January-February; 22(1): 7-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617444&dopt=Abstract

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Inflammatory cytokines, C reactive protein, and procalcitonin as early predictors of necrosis infection in acute necrotizing pancreatitis. Author(s): Riche FC, Cholley BP, Laisne MJ, Vicaut E, Panis YH, Lajeunie EJ, Boudiaf M, Valleur PD. Source: Surgery. 2003 March; 133(3): 257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660636&dopt=Abstract

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Interleukin 18 levels reflect the severity of acute pancreatitis. Author(s): Endo S, Inoue Y, Fujino Y, Wakabayashi G, Inada K, Sato S. Source: Res Commun Mol Pathol Pharmacol. 2001; 110(5-6): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889520&dopt=Abstract

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Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. Author(s): Rahman SH, Ammori BJ, Holmfield J, Larvin M, McMahon MJ. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 January; 7(1): 26-35; Discussion 35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559182&dopt=Abstract

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Intraductal papillary mucinous neoplasm of the pancreas presenting as acute pancreatitis. Author(s): Krishna M, Banner BF, Puyana JC, Khan A. Source: Archives of Pathology & Laboratory Medicine. 1996 October; 120(10): 981-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046614&dopt=Abstract

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Intrahepatic hemorrhage and subcapsular hematoma developing in acute pancreatitis. Author(s): Lin CK, Chen CH, Yeh CH, Lin SL, Tsang YM, Sheu JC. Source: Hepatogastroenterology. 2003 March-April; 50(50): 571-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749275&dopt=Abstract

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Intramural duodenal hematoma and acute pancreatitis. Author(s): Bodnar Z, Varvolgyi C. Source: Endoscopy. 2003 August; 35(8): 708; Author Reply 708. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929071&dopt=Abstract

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Is pancreaticoduodenectomy justified for chronic pancreatitis masquerading as periampullary tumor? Author(s): Shyr YM, Su CH, Wu CW, Lui WY. Source: Hepatogastroenterology. 2003 July-August; 50(52): 1163-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846005&dopt=Abstract

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Ischemic-appearing papillitis in a patient with gallstone pancreatitis and cholangitis. Author(s): Yarze JC. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 741-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741464&dopt=Abstract

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Jejunal feeding in chronic pancreatitis with severe necrosis. Author(s): Hamvas J, Schwab R, Pap A. Source: Jop [electronic Resource] : Journal of the Pancreas. 2001 May; 2(3): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870333&dopt=Abstract

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Juvenile idiopathic fibrosing pancreatitis. Author(s): Sclabas G, Kirschstein T, Uhl W, Hurlimann R, Ruchti C, Buchler MW. Source: Digestive Diseases and Sciences. 2002 June; 47(6): 1230-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064796&dopt=Abstract

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Lamivudine treatment for recurrent pancreatitis associated with reactivation of chronic B hepatitis. Author(s): Chen CH, Changchien CS, Lu SN, Wang JH, Hung CH, Lee CM. Source: Digestive Diseases and Sciences. 2002 March; 47(3): 564-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911343&dopt=Abstract

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Laparoscopic cholecystectomy: are patients with biliary pancreatitis at increased operative risk? Author(s): Ammori BJ, Davides D, Vezakis A, Larvin M, McMahon MJ. Source: Surgical Endoscopy. 2003 May; 17(5): 777-80. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984675&dopt=Abstract

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Laparoscopic pancreatic surgery in patients with chronic pancreatitis. Author(s): Fernandez-Cruz L, Saenz A, Astudillo E, Pantoja JP, Uzcategui E, Navarro S. Source: Surgical Endoscopy. 2002 June; 16(6): 996-1003. Epub 2002 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163971&dopt=Abstract

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Laser microdissection of small tissue samples--application to chronic pancreatitis tissues. Author(s): Heinmoller E, Bockholt A, Werther M, Ziemer M, Muller A, Ghadimi BM, Ruschoff J. Source: Pathology, Research and Practice. 2003; 199(6): 363-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924436&dopt=Abstract

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Late mortality in patients with severe acute pancreatitis. Author(s): Senapati PS, Ammori BJ. Source: The British Journal of Surgery. 2002 April; 89(4): 491; Author Reply 491. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952601&dopt=Abstract

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Leptin modulates the inflammatory response in acute pancreatitis. Author(s): Konturek PC, Jaworek J, Maniatoglou A, Bonior J, Meixner H, Konturek SJ, Hahn EG. Source: Digestion. 2002; 65(3): 149-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138320&dopt=Abstract

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Letter 1: Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis (Br J Surg 2002; 89: 11031107). Author(s): Weale R, Edwards A. Source: The British Journal of Surgery. 2003 January; 90(1): 122-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520591&dopt=Abstract

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Letter 2: Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis (Br J Surg 2002; 89: 11031107). Author(s): Rahman SH, Catton JA, McMahon MJ. Source: The British Journal of Surgery. 2003 January; 90(1): 123. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520593&dopt=Abstract

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Levels of the chemokines growth-related oncogene alpha and epithelial neutrophilactivating protein 78 are raised in patients with severe acute pancreatitis (Br J Surg 2002; 89: 566-72). Author(s): Makhija R, Kingsnorth AN. Source: The British Journal of Surgery. 2002 September; 89(9): 1194. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190691&dopt=Abstract

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Levels of the chemokines growth-related oncogene alpha and epithelial neutrophilactivating protein 78 are raised in patients with severe acute pancreatitis. Author(s): Shokuhi S, Bhatia M, Christmas S, Sutton R, Neoptolemos JP, Slavin J. Source: The British Journal of Surgery. 2002 May; 89(5): 566-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972545&dopt=Abstract

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Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials. Author(s): Abu-Zidan FM, Windsor JA. Source: The European Journal of Surgery = Acta Chirurgica. 2002; 168(4): 215-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440758&dopt=Abstract

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Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis: a report from the United States. Author(s): Schneider A, Pfutzer RH, Barmada MM, Slivka A, Martin J, Whitcomb DC. Source: Digestive Diseases and Sciences. 2003 June; 48(6): 1110-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822871&dopt=Abstract

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Lipase and pancreatic amylase versus total amylase as biomarkers of pancreatitis: an analytical investigation. Author(s): Moridani MY, Bromberg IL. Source: Clinical Biochemistry. 2003 February; 36(1): 31-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554057&dopt=Abstract

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Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis. Author(s): Athyros VG, Giouleme OI, Nikolaidis NL, Vasiliadis TV, Bouloukos VI, Kontopoulos AG, Eugenidis NP. Source: Journal of Clinical Gastroenterology. 2002 April; 34(4): 472-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907366&dopt=Abstract

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Long-term health-related quality of life in survivors of severe acute pancreatitis. Author(s): Halonen KI, Pettila V, Leppaniemi AK, Kemppainen EA, Puolakkainen PA, Haapiainen RK. Source: Intensive Care Medicine. 2003 May; 29(5): 782-6. Epub 2003 April 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684744&dopt=Abstract

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Long-term results of distal pancreatectomy for chronic pancreatitis in 90 patients. Author(s): Hutchins RR, Hart RS, Pacifico M, Bradley NJ, Williamson RC. Source: Annals of Surgery. 2002 November; 236(5): 612-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409667&dopt=Abstract

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Lung injury in acute pancreatitis: mechanisms, prevention, and therapy. Author(s): Shields CJ, Winter DC, Redmond HP. Source: Current Opinion in Critical Care. 2002 April; 8(2): 158-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386518&dopt=Abstract

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Lymphoplasmacytic chronic cholecystitis and biliary tract disease in patients with lymphoplasmacytic sclerosing pancreatitis. Author(s): Abraham SC, Cruz-Correa M, Argani P, Furth EE, Hruban RH, Boitnott JK. Source: The American Journal of Surgical Pathology. 2003 April; 27(4): 441-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657928&dopt=Abstract

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Lymphoplasmacytic sclerosing pancreatitis and cholangitis. Author(s): Kram MT, May LD, Cooperman A, Bernstein S, Abedeer R, Cohen PR. Source: Gastrointestinal Endoscopy. 2002 April; 55(4): 588-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923781&dopt=Abstract

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Lymphoplasmacytic sclerosing pancreatitis: inflammatory mimic of pancreatic carcinoma. Author(s): Weber SM, Cubukcu-Dimopulo O, Palesty JA, Suriawinata A, Klimstra D, Brennan MF, Conlon K. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 January; 7(1): 129-37; Discussion 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559194&dopt=Abstract

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Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis. Author(s): Sakai Y, Masamune A, Satoh A, Nishihira J, Yamagiwa T, Shimosegawa T. Source: Gastroenterology. 2003 March; 124(3): 725-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612911&dopt=Abstract

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Main pancreatic duct: morphlogy after acute biliary pancreatitis with magnetic resonance cholangiopancreatography after secretin stimulation. Author(s): Pareja E, Artigues E, Mir J, Fabra R, Martinez V, Vazquez A, Trullenque R. Source: Rev Esp Enferm Dig. 2003 June; 95(6): 395-400, 389-94. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852778&dopt=Abstract

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Management of gallstone pancreatitis in Auckland: progress and compliance. Author(s): Ong SK, Christie PM, Windsor JA. Source: Anz Journal of Surgery. 2003 April; 73(4): 194-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662225&dopt=Abstract

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Management of infection in acute pancreatitis. Author(s): Hartwig W, Werner J, Uhl W, Buchler MW. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2002; 9(4): 423-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483263&dopt=Abstract

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Management of pain in chronic pancreatitis: medical or surgical. Author(s): Agarwal N, Pitchumoni CS. Source: Journal of Clinical Gastroenterology. 2003 February; 36(2): 98-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544189&dopt=Abstract

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Management of severe acute pancreatitis. Author(s): Yousaf M, McCallion K, Diamond T. Source: The British Journal of Surgery. 2003 April; 90(4): 407-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673741&dopt=Abstract

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Matrix metalloproteinase-1 and cytokines in patients with acute pancreatitis. Author(s): Nakae H, Endo S, Inoue Y, Fujino Y, Wakabayashi G, Inada K, Sato S. Source: Pancreas. 2003 March; 26(2): 134-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604910&dopt=Abstract

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Mechanical prevention of post-ERCP pancreatitis by pancreatic stents: results, techniques, and indications. Author(s): Tarnasky PR. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 January; 4(1): 58-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555017&dopt=Abstract

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Medical therapy for chronic pancreatitis pain. Author(s): Singh VV, Toskes PP. Source: Current Gastroenterology Reports. 2003 April; 5(2): 110-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631450&dopt=Abstract

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Metronidazole-induced pancreatitis in a patient with recurrent vaginal trichomoniasis. Author(s): Feola DJ, Thornton AC. Source: Pharmacotherapy. 2002 November; 22(11): 1508-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432979&dopt=Abstract

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Minute pancreatic carcinoma with initial symptom of acute pancreatitis. Author(s): Imamura M, Asahi S, Yamauchi H, Tadokoro K, Suzuki H. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2002; 9(5): 632-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541052&dopt=Abstract

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Mirtazapine: another drug responsible for drug-induced acute pancreatitis? A letter of warning. Author(s): Lankisch PG, Werner HM. Source: Pancreas. 2003 March; 26(2): 211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604923&dopt=Abstract

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Modern phase-specific management of acute pancreatitis. Author(s): Werner J, Uhl W, Hartwig W, Hackert T, Muller C, Strobel O, Buchler MW. Source: Digestive Diseases (Basel, Switzerland). 2003; 21(1): 38-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837999&dopt=Abstract

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Molecular alterations in chronic pancreatitis. Author(s): Kayed H, Muller M, Kleeff J, Bockman DE, Buchler MW, Friess H. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2002; 9(6): 653-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658397&dopt=Abstract

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Molecular pathophysiology of pancreatitis. Author(s): Naruse S. Source: Intern Med. 2003 March; 42(3): 288-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705799&dopt=Abstract

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Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Author(s): Logsdon CD, Simeone DM, Binkley C, Arumugam T, Greenson JK, Giordano TJ, Misek DE, Kuick R, Hanash S. Source: Cancer Research. 2003 May 15; 63(10): 2649-57. Erratum In: Cancer Res. 2003 June 15; 63(12): 3445. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750293&dopt=Abstract

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Motion--pancreatic endoscopy is useful for the pain of chronic pancreatitis: arguments against the motion. Author(s): Conwell DL. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 January; 17(1): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560858&dopt=Abstract

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Motion--pancreatic endoscopy is useful for the pain of chronic pancreatitis: arguments for the motion. Author(s): Branch SM. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 January; 17(1): 57-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560857&dopt=Abstract

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Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis. Author(s): Chandak GR, Idris MM, Reddy DN, Bhaskar S, Sriram PV, Singh L. Source: Journal of Medical Genetics. 2002 May; 39(5): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011155&dopt=Abstract

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Mutations of the serine protease inhibitor, Kazal type 1 gene, in patients with idiopathic chronic pancreatitis. Author(s): Truninger K, Witt H, Kock J, Kage A, Seifert B, Ammann RW, Blum HE, Becker M. Source: The American Journal of Gastroenterology. 2002 May; 97(5): 1133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014716&dopt=Abstract

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N34S, a pancreatitis associated SPINK1 mutation, is not associated with sporadic pancreatic cancer. Author(s): Teich N, Schulz HU, Witt H, Bohmig M, Keim V. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2003; 3(1): 67-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649567&dopt=Abstract

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Natural course of chronic pancreatitis. Author(s): Lankisch PG. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(1): 3-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120264&dopt=Abstract

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Natural history of pancreatitis associated with cystic fibrosis gene mutations. Author(s): Frulloni L, Castellani C, Bovo P, Vaona B, Calore B, Liani C, Mastella G, Cavallini G. Source: Dig Liver Dis. 2003 March; 35(3): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779072&dopt=Abstract

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Necrosectomy followed by closed cavity lavage for necrotising pancreatitis--report of three cases. Author(s): Ali M, Zafar SM, Fazal NM, Zaman B, Husain M, Rahman A, Ahmed B, Islam MM. Source: Bangladesh Med Res Counc Bull. 2001 December; 27(3): 112-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197625&dopt=Abstract

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Necrotizing acute pancreatitis induced by Salmonella typhimurium. Author(s): Blank A, Maybody M, Isom-Batz G, Roslin M, Dillon EH. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1472-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924638&dopt=Abstract

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Necrotizing pancreatitis during pregnancy: a rare cause and review of the literature. Author(s): Gosnell FE, O'Neill BB, Harris HW. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2001 July-August; 5(4): 371-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985977&dopt=Abstract

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Neural alterations in surgical stage chronic pancreatitis are independent of the underlying aetiology. Author(s): Friess H, Shrikhande S, Shrikhande M, Martignoni M, Kulli C, Zimmermann A, Kappeler A, Ramesh H, Buchler M. Source: Gut. 2002 May; 50(5): 682-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950816&dopt=Abstract

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Neuropharmacological factors, biliary motility and pancreatitis. Author(s): Lechin F, van der Dijs B, Lechin ME. Source: Jop [electronic Resource] : Journal of the Pancreas. 2002 September; 3(5): 152-4; Author Reply 155. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221330&dopt=Abstract

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New frontiers in the pharmacological prevention of post-ERCP pancreatitis: the cytokines. Author(s): Demols A, Deviere J. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 January; 4(1): 49-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555016&dopt=Abstract

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New laboratory tests in acute pancreatitis. Author(s): Kylanpaa-Back ML, Repo H, Kemppainen E. Source: Addiction Biology. 2002 April; 7(2): 181-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006214&dopt=Abstract

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Nifedipine for prevention of post-ERCP pancreatitis: a prospective, double-blind randomized study. Author(s): Prat F, Amaris J, Ducot B, Bocquentin M, Fritsch J, Choury AD, Pelletier G, Buffet C. Source: Gastrointestinal Endoscopy. 2002 August; 56(2): 202-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145597&dopt=Abstract

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Non-compliance with national guidelines in the management of acute pancreatitis in the United kingdom. Author(s): Aly EA, Milne R, Johnson CD. Source: Digestive Surgery. 2002; 19(3): 192-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119521&dopt=Abstract

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Nonocclusive visceral ischemia associated with severe acute pancreatitis. Author(s): Yasuda T, Takeyama Y, Ueda T, Hori Y, Nishikawa J, Kuroda Y. Source: Pancreas. 2003 January; 26(1): 95-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499925&dopt=Abstract

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Nontraumatic pancreatitis in spinal cord injury. Author(s): Nobel D, Baumberger M, Eser P, Michel D, Knecht H, Stocker R. Source: Spine. 2002 May 1; 27(9): E228-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979180&dopt=Abstract

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Nutrition support during acute pancreatitis. Author(s): Abou-Assi S, O'Keefe SJ. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 November-December; 18(11-12): 938-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431714&dopt=Abstract

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Nutritional management of acute pancreatitis. Author(s): Fang J, DiSario JA. Source: Current Gastroenterology Reports. 2002 April; 4(2): 120-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900676&dopt=Abstract

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Nutritional support in acute pancreatitis. Author(s): McClave SA. Source: Nestle Nutr Workshop Ser Clin Perform Programme. 2003; (8): 207-15; Discussion 215-21. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968456&dopt=Abstract

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Obesity and treatment of diabetes with glyburide may both be risk factors for acute pancreatitis. Author(s): Blomgren KB, Sundstrom A, Steineck G, Wiholm BE. Source: Diabetes Care. 2002 February; 25(2): 298-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815499&dopt=Abstract

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Octreotide versus hydrocortisone versus placebo in the prevention of post-ERCP pancreatitis: a multicenter randomized controlled trial. Author(s): Manolakopoulos S, Avgerinos A, Vlachogiannakos J, Armonis A, Viazis N, Papadimitriou N, Mathou N, Stefanidis G, Rekoumis G, Vienna E, Tzourmakliotis D, Raptis SA. Source: Gastrointestinal Endoscopy. 2002 April; 55(4): 470-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923756&dopt=Abstract

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On the role of CFTR, PSSR1 and PST1/SPINK1 in idiopathic chronic pancreatitis. Author(s): Perri F, Piepoli A, Andriulli A. Source: European Journal of Human Genetics : Ejhg. 2003 February; 11(2): 107; Author Reply 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634855&dopt=Abstract

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Optimizing surgical therapy for chronic pancreatitis. Author(s): Knoefel WT, Eisenberger CF, Strate T, Izbicki JR. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2002; 2(4): 379-84; Discussion 385. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138226&dopt=Abstract

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Organ-preserving pancreatic head resection in chronic pancreatitis. Author(s): Farkas G, Leindler L, Daroczi M, Farkas G Jr. Source: The British Journal of Surgery. 2003 January; 90(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520571&dopt=Abstract

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Osteopontin expression in chronic pancreatitis. Author(s): Nakamura M, Oka M, Iizuka N, Kawauchi S, Gondo T, Ueno T, Tangoku A. Source: Pancreas. 2002 August; 25(2): 182-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142743&dopt=Abstract

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Outcome after duodenum-preserving pancreatic head resection is improved compared with classic Whipple procedure in the treatment of chronic pancreatitis. Author(s): Witzigmann H, Max D, Uhlmann D, Geissler F, Schwarz R, Ludwig S, Lohmann T, Caca K, Keim V, Tannapfel A, Hauss J. Source: Surgery. 2003 July; 134(1): 53-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874583&dopt=Abstract

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Outcome analysis of patients with acute pancreatitis by using an artificial neural network. Author(s): Keogan MT, Lo JY, Freed KS, Raptopoulos V, Blake S, Kamel IR, Weisinger K, Rosen MP, Nelson RC. Source: Academic Radiology. 2002 April; 9(4): 410-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942655&dopt=Abstract

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Outcome and quality of life in chronic pancreatitis. Author(s): Talamini G, Bassi C, Butturini G, Falconi M, Casetti L, Gumbus AA, Carrara S, Fantin A, Pederzoli P. Source: Jop [electronic Resource] : Journal of the Pancreas. 2001 July; 2(4): 117-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875248&dopt=Abstract

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Outcome of necrosectomy in acute pancreatitis: the case for continued vigilance. Author(s): Beattie GC, Mason J, Swan D, Madhavan KK, Siriwardena AK. Source: Scandinavian Journal of Gastroenterology. 2002 December; 37(12): 1449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523596&dopt=Abstract

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Outcome of pancreaticojejunostomy after previous endoscopic stenting in patients with chronic pancreatitis. Author(s): Boerma D, van Gulik TM, Rauws EA, Obertop H, Gouma DJ. Source: The European Journal of Surgery = Acta Chirurgica. 2002; 168(4): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440760&dopt=Abstract

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Overexpression of pancreatitis-associated protein (PAP) in human pancreatic ductal adenocarcinoma. Author(s): Xie MJ, Motoo Y, Iovanna JL, Su SB, Ohtsubo K, Matsubara F, Sawabu N. Source: Digestive Diseases and Sciences. 2003 March; 48(3): 459-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757156&dopt=Abstract

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p53 protein expression and CA19.9 values in differential cytological diagnosis of pancreatic cancer complicated with chronic pancreatitis and chronic pancreatitis. Author(s): Mu DQ, Wang GF, Peng SY. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1815-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918127&dopt=Abstract

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Pancreas divisum and intraductal papillary mucinous tumor occurring simultanously in a patient presenting with recurrent acute pancreatitis. Author(s): Yarze JC, Chase MP, Herlihy KJ, Nawras A. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772789&dopt=Abstract

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Pancreas divisum: an uncommon cause of acute pancreatitis. Author(s): Mishra D, Singh R, Kohli A. Source: Indian J Pediatr. 2003 July; 70(7): 593-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940385&dopt=Abstract

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Pancreatectomy with islet autotransplantation for the treatment of severe chronic pancreatitis: the first 40 patients at the leicester general hospital. Author(s): Clayton HA, Davies JE, Pollard CA, White SA, Musto PP, Dennison AR. Source: Transplantation. 2003 July 15; 76(1): 92-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865792&dopt=Abstract

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Pancreatic cancer after surgery for chronic pancreatitis. Author(s): Sakorafas GH, Sarr MG. Source: Dig Liver Dis. 2003 July; 35(7): 482-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870734&dopt=Abstract

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Pancreatitis in an HIV-infected person on a tenofovir, didanosine and stavudine containing highly active antiretroviral treatment. Author(s): Callens S, De Schacht C, Huyst V, Colebunders R. Source: The Journal of Infection. 2003 August; 47(2): 188-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860159&dopt=Abstract

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Pancreatitis leading to retroperitoneal fibrosis and ureteric obstruction. Author(s): Tan HM, Khoo J, Pang KP. Source: Med J Malaysia. 2003 June; 58(2): 286-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14569752&dopt=Abstract

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Pathophysiology of acute pancreatitis: a multistep disease. Author(s): Frossard JL. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 166-73. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891927&dopt=Abstract

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Pediatric acute pancreatitis--deciphering the black box. Author(s): Brown A. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 100-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869877&dopt=Abstract

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Postoperative enteral stimulation by gut feeding improves outcomes in severe acute pancreatitis. Author(s): Austrums E, Pupelis G, Snippe K. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 June; 19(6): 487-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781846&dopt=Abstract

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Pro/con clinical debate: antibiotics are important in the management of patients with pancreatitis with evidence of pancreatic necrosis. Author(s): Ramsay G, Breedveld P, Blackbourne LH, Cohn SM. Source: Critical Care (London, England). 2003 October; 7(5): 351-3. Epub 2003 March 17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974967&dopt=Abstract

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Quality of life after bilateral thoracoscopic splanchnicectomy: long-term evaluation in patients with chronic pancreatitis. Author(s): Howard TJ, Swofford JB, Wagner DL, Sherman S, Lehman GA. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 November-December; 6(6): 845-52; Discussion 853-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504223&dopt=Abstract

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Quality of life improvement after videothoracoscopic splanchnicectomy in chronic pancreatitis patients: case control study. Author(s): Makarewicz W, Stefaniak T, Kossakowska M, Basinski A, Suchorzewski M, Stanek A, Gruca ZB. Source: World Journal of Surgery. 2003 August; 27(8): 906-11. Epub 2003 June 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822048&dopt=Abstract

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Quality of life in chronic pancreatitis: a prospective trial comparing classical whipple procedure and duodenum-preserving pancreatic head resection. Author(s): Witzigmann H, Max D, Uhlmann D, Geissler F, Ludwig S, Schwarz R, Krauss O, Lohmann T, Keim V, Hauss J. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 March-April; 6(2): 173-9; Discussion 179-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992802&dopt=Abstract

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Re: Lankisch et al.: the role of hematocrit as a prognostic factor in newly diagnosed acute pancreatitis. Author(s): Shuhaiber J. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1839; Author Reply 1839-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135048&dopt=Abstract

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Recurrent pancreatitis as a late complication of endoscopic sphincterotomy for common bile duct stones: diagnosis and therapy. Author(s): Rolny P, Andren-Sandberg A, Falk A. Source: Endoscopy. 2003 April; 35(4): 356-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664395&dopt=Abstract

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Recurrent thrombotic thrombocytopenic purpura (TTP) as a complication of acute relapsing pancreatitis. Author(s): Talwalkar JA, Ruymann FW, Marcoux P, Farraye FA. Source: Digestive Diseases and Sciences. 2002 May; 47(5): 1096-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018906&dopt=Abstract

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Reduction in mortality with delayed surgical therapy of severe pancreatitis. Author(s): Hartwig W, Maksan SM, Foitzik T, Schmidt J, Herfarth C, Klar E. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 May-June; 6(3): 481-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023003&dopt=Abstract

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Reduction in the incidence of pancreatitis in patients undergoing sphincter of Oddi manometry: a successful quality improvement project. Author(s): Bin-Sagheer ST, Brady PG, Mamel JJ, Robinson B. Source: Southern Medical Journal. 2003 March; 96(3): 223-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659351&dopt=Abstract

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Remifentanil for the pain of pancreatitis. Author(s): Gopal ST, Lane MP, Park GR. Source: Anaesthesia. 2003 November; 58(11): 1137-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14616623&dopt=Abstract

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Results of treating severe acute pancreatitis with gabexate is associated with neutrophil apoptosis activity. Author(s): Chiu DF, Chen JC, Chen HM, Ng CJ, Shyr MH, Chen MF. Source: Hepatogastroenterology. 2003 March-April; 50(50): 553-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749271&dopt=Abstract

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Role of ERCP in acute pancreatitis. Author(s): Kozarek R. Source: Gastrointestinal Endoscopy. 2002 December; 56(6 Suppl): S231-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447273&dopt=Abstract

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Role of oxygen free radicals in patients with acute pancreatitis. Author(s): Park BK, Chung JB, Lee JH, Suh JH, Park SW, Song SY, Kim H, Kim KH, Kang JK. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2266-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562390&dopt=Abstract

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Role of the gut in the course of severe acute pancreatitis. Author(s): Ammori BJ. Source: Pancreas. 2003 March; 26(2): 122-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604908&dopt=Abstract

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Secretin-stimulated magnetic resonance pancreaticogram to assess pancreatic duct outflow obstruction in evaluation of idiopathic acute recurrent pancreatitis: a pilot study. Author(s): Khalid A, Peterson M, Slivka A. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924639&dopt=Abstract

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Self-expandable metal mesh stents for common bile duct stenosis in chronic pancreatitis: retrospective evaluation of long-term follow-up and clinical outcome pilot study. Author(s): Eickhoff A, Jakobs R, Leonhardt A, Eickhoff JC, Riemann JF. Source: Zeitschrift Fur Gastroenterologie. 2003 July; 41(7): 649-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908456&dopt=Abstract

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Sequential changes in pancreatic markers in acute pancreatitis. Author(s): Lempinen M, Stenman UH, Puolakkainen P, Hietaranta A, Haapiainen R, Kemppainen E. Source: Scandinavian Journal of Gastroenterology. 2003 June; 38(6): 666-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825877&dopt=Abstract

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Severe acute necrotizing pancreatitis associated with lipoprotein lipase deficiency in childhood. Author(s): van Walraven LA, de Klerk JB, Postema RR. Source: Journal of Pediatric Surgery. 2003 September; 38(9): 1407-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523833&dopt=Abstract

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Severe acute pancreatitis associated with acute hepatitis A: a case report. Author(s): Batra Y, Chakravarty S, Bhatt G. Source: Trop Gastroenterol. 2003 January-March; 24(1): 27-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974212&dopt=Abstract

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Severe acute pancreatitis due to hepatitis A virus infection in a patient of acute viral hepatitis. Author(s): Khanna S, Vij JC. Source: Trop Gastroenterol. 2003 January-March; 24(1): 25-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974211&dopt=Abstract

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Single-stage definitive laparoscopic management in mild acute biliary pancreatitis. Author(s): Isla A, Griniatsos J, Rodway A. Source: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2003 April; 13(2): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737719&dopt=Abstract

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State-of-the-art imaging of acute pancreatitis. Author(s): Mortele KJ, Banks PA, Silverman SG. Source: Jbr-Btr. 2003 July-August; 86(4): 193-208. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527059&dopt=Abstract

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Surgical treatment of necrotizing pancreatitis and complicated forms of cholecystopancreatitis. Author(s): Nedev PI, Uchikov AP, Novakov IP, Murdjev KA, Uchikov PA, Iliev YT, Todorov BE. Source: Folia Med (Plovdiv). 2003; 45(2): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943049&dopt=Abstract

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Surgical treatment of severe acute pancreatitis: timing of operation is crucial for survival. Author(s): Gotzinger P, Wamser P, Exner R, Schwanzer E, Jakesz R, Fugger R, Sautner T. Source: Surgical Infections. 2003 Summer; 4(2): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906721&dopt=Abstract

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The course of genetically determined chronic pancreatitis. Author(s): Keim V, Witt H, Bauer N, Bodeker H, Rosendahl J, Teich N, Mossner J. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 July; 4(4): 146-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853682&dopt=Abstract

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The disease concept of chronic pancreatitis, past, present and future. Author(s): Hayakawa T. Source: Intern Med. 2003 March; 42(3): 219. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705784&dopt=Abstract

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The problem of diagnosing chronic pancreatitis. Author(s): Lankisch PG. Source: Dig Liver Dis. 2003 March; 35(3): 131-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779064&dopt=Abstract

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The race from chronic pancreatitis to pancreatic cancer. Author(s): Cavestro GM, Comparato G, Nouvenne A, Sianesi M, Di Mario F. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 September; 4(5): 165-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526127&dopt=Abstract

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The Zollinger-Ellison syndrome with acute bleeding pancreatitis. Author(s): Yamamoto M, Mine H, Maehara Y, Sugimachi K. Source: Hepatogastroenterology. 2003 March-April; 50(50): 430-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749240&dopt=Abstract

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Thrombotic thrombocytopenic purpura (TTP) presenting as pancreatitis. Author(s): Muniz AE, Barbee RW. Source: The Journal of Emergency Medicine. 2003 May; 24(4): 407-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745043&dopt=Abstract

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Transplant pancreatitis after liver plus bowel transplantation. Author(s): Pirenne J, Coosemans W, Aerts R, Monbaliu D, Van Steenbergen W, Koshiba T. Source: Transplantation Proceedings. 2002 May; 34(3): 885-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034222&dopt=Abstract

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Treatment of menstruation-associated recurrence of hereditary pancreatitis with pharmacologic ovarian suppression. Author(s): Heinig J, Simon P, Weiss FU, Zimmer KP, Domschke W, Lerch MM. Source: The American Journal of Medicine. 2002 August 1; 113(2): 164. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133758&dopt=Abstract

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Trypsinogen-2 and trypsinogen activation peptide (TAP) in urine of patients with acute pancreatitis. Author(s): Lempinen M, Stenman UH, Finne P, Puolakkainen P, Haapiainen R, Kemppainen E. Source: The Journal of Surgical Research. 2003 May 15; 111(2): 267-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850473&dopt=Abstract

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Tumor-associated focal chronic pancreatitis from invasion of the pancreatic duct by common bile duct carcinoma: radiologic-pathologic correlation. Author(s): Gabata T, Sanada J, Kobayashi S, Terayama N, Kadoya M, Matsui O. Source: Abdominal Imaging. 2003 May-June; 28(3): 378-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719908&dopt=Abstract

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UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of chronic pancreatitis and pancreatic cancer. Author(s): Ockenga J, Vogel A, Teich N, Keim V, Manns MP, Strassburg CP. Source: Gastroenterology. 2003 June; 124(7): 1802-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806614&dopt=Abstract

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Ultrasound guided thrombin injection to treat a pseudoaneurysm secondary to chronic pancreatitis. Author(s): Armstrong EM, Edwards A, Kingsnorth AN, Freeman S, Roobottom CA. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2003 October; 26(4): 448-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512011&dopt=Abstract

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Unraveling the mystery of acute pancreatitis. Author(s): Cole L. Source: Dimensions of Critical Care Nursing : Dccn. 2002 May-June; 21(3): 86-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042691&dopt=Abstract

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Unresolved issues about post-ERCP pancreatitis: an overview. Author(s): Testoni PA. Source: Jop [electronic Resource] : Journal of the Pancreas. 2002 November; 3(6): 156-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432181&dopt=Abstract

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Upper gastrointestinal bleeding in tropical pancreatitis due to pseudoaneurysm rupture. Author(s): Sreedharan VK, Shenoy KR, Shenoy MG. Source: Trop Doct. 2003 January; 33(1): 57. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568530&dopt=Abstract

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Up-regulation of p75 neurotrophin receptor (p75NTR) is associated with apoptosis in chronic pancreatitis. Author(s): Zhu Z, Friess H, Shi X, Wang L, di Mola FF, Wirtz M, Hartel M, Wagner M, Zimmermann A, Muller M, Buchler MW. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 717-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741461&dopt=Abstract

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Urinary trypsinogen activation peptide is more accurate than hematocrit in determining severity in patients with acute pancreatitis: a prospective study. Author(s): Khan Z, Vlodov J, Horovitz J, Jose RM, Iswara K, Smotkin J, Brown A, Tenner S. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 1973-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190163&dopt=Abstract

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Ursodeoxycholic acid as an alternative therapy for autoimmune pancreatitis. Author(s): Okazaki K. Source: Intern Med. 2002 December; 41(12): 1082-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521187&dopt=Abstract

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Use of endoscopic naso-pancreatic drainage in the treatment of severe acute pancreatitis. Author(s): Quan ZF, Wang ZM, Li WQ, Li JS. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 868-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679951&dopt=Abstract

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Usefulness of endoscopic observation of the main duodenal papilla in the diagnosis of sclerosing pancreatitis. Author(s): Unno H, Saegusa H, Fukushima M, Hamano H. Source: Gastrointestinal Endoscopy. 2002 December; 56(6): 880-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447302&dopt=Abstract

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Value of MR pancreatography in the evaluation of patients with chronic pancreatitis. Author(s): Varghese JC, Masterson A, Lee MJ. Source: Clinical Radiology. 2002 May; 57(5): 393-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014938&dopt=Abstract

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Variations in implementation of current national guidelines for the treatment of acute pancreatitis: implications for acute surgical service provision. Author(s): Barnard J, Siriwardena AK. Source: Annals of the Royal College of Surgeons of England. 2002 March; 84(2): 79-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995768&dopt=Abstract

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Visualization of the heterogeneous internal structure of so-called “pancreatic necrosis” by magnetic resonance imaging in acute necrotizing pancreatitis. Author(s): Hirota M, Kimura Y, Ishiko T, Beppu T, Yamashita Y, Ogawa M. Source: Pancreas. 2002 July; 25(1): 63-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131773&dopt=Abstract

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Vitamin D3 in patients with various grades of chronic pancreatitis, according to morphological and functional criteria of the pancreas. Author(s): Mann ST, Stracke H, Lange U, Klor HU, Teichmann J. Source: Digestive Diseases and Sciences. 2003 March; 48(3): 533-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757166&dopt=Abstract

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Wall stent-enhanced lateral pancreaticojejunostomy for small-duct pancreatitis. Author(s): Madura JA, Canal DF, Lehman GA. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 June; 138(6): 644-9; Discussion 649-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799336&dopt=Abstract

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Wandering spleen presenting as acute pancreatitis in pregnancy. Author(s): Gilman RS, Thomas RL. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 2): 1100-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738115&dopt=Abstract

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Wegener's granulomatosis with onset of acute pancreatitis and rapid progress. A case report. Author(s): Matsubayashi H, Seki T, Niki S, Mizumura Y, Taguchi Y, Moriyasu F, Go K. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(3): 263-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120205&dopt=Abstract

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Wernicke's encephalopathy: a complication of acute pancreatitis? Author(s): Lee YD, Lee SO, Lee ST. Source: Hosp Med. 2003 June; 64(6): 372-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833836&dopt=Abstract

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What are the predictors of post-ERCP pancreatitis, and how useful are they? Author(s): Sultan S, Baillie J. Source: Jop [electronic Resource] : Journal of the Pancreas. 2002 November; 3(6): 188-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432185&dopt=Abstract

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What is the risk of alcoholic pancreatitis in heavy drinkers? Author(s): Lankisch PG, Lowenfels AB, Maisonneuve P. Source: Pancreas. 2002 November; 25(4): 411-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409838&dopt=Abstract

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What should be done with idiopathic recurrent pancreatitis that remains 'idiopathic' after standard investigation? Author(s): Baillie J. Source: Jop [electronic Resource] : Journal of the Pancreas. 2001 November; 2(6): 401-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880699&dopt=Abstract

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Whole gut washout ameliorates progression of acute experimental pancreatitis. Author(s): Lange JF. Source: American Journal of Surgery. 2002 January; 183(1): 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869715&dopt=Abstract

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Why clinical trials might succeed in acute pancreatitis when they failed in septic shock. Author(s): Frossard JL, Morel P, Pastor CM. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 January; 4(1): 11-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555010&dopt=Abstract

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

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

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

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The following is a typical result when searching for recently indexed consumer information on pancreatitis: •

Enteral nutrition in acute pancreatitis. Author(s): Division of Digestive Disease and Nutrition, University of Massachusetts Medical Center, Worcester 01655, USA. Source: Karamitsios, N Saltzman, J R Nutr-Revolume 1997 July; 55(7): 279-82 0029-6643

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Evidence of primary beta-cell destruction by T-cells and beta-cell differentiation from pancreatic ductal cells in diabetes associated with active autoimmune chronic pancreatitis. Author(s): Department of Endocrinology and Metabolism, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan. Source: Tanaka, S Kobayashi, T Nakanishi, K Okubo, M Murase, T Hashimoto, M Watanabe, G Matsushita, H Endo, Y Yoshizaki, H Kosuge, T Sakamoto, M Takeuchi, K Diabetes-Care. 2001 September; 24(9): 1661-7 0149-5992

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

Animal model of acute pancreatitis induced by synthetic prooxidant. Author(s): Medical University, Gdansk (Poland) I.N.R.C.A. and Biancalana Mazera Foundation, Ancona (Italy) Ancona University, (Italy) Source: Sledzinski, Z. Stanek, A. Wajda, Z. Wozniak, M. Brunelli, A. Scutti, G. Bertoil, E. Lezoche, E. Polish-Journal-of-Environmental-Studies (Poland). (1998). volume 7(6) page 373.

Additional physician-oriented references include: •

Absence of endogenous interleukin-6 enhances the inflammatory response during acute pancreatitis induced by cerulein in mice. Author(s): Institute of Pharmacology, School of Medicine, University of Messina, Italy. [email protected] Source: Cuzzocrea, S Mazzon, E Dugo, L Centorrino, T Ciccolo, A McDonald, M C de Sarro, A Caputi, A P Thiemermann, C Cytokine. 2002 June 7; 18(5): 274-85 1043-4666

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Acute pancreatitis after morphine administration. Source: Famularo, G Pozzessere, C Polchi, S De Simone, C Ital-J-Gastroenterol-Hepatol. 1999 Aug-September; 31(6): 522-3 1125-8055

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Acute pancreatitis in a multi-ethnic population. Author(s): Department of Surgery, Perak College of Medicine, Malaysia. [email protected] Source: Kandasami, P Harunarashid, H Kaur, H Singapore-Med-J. 2002 June; 43(6): 2848 0037-5675

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Acute pancreatitis secondary to isotretinoin-induced hyperlipidemia. Author(s): St. Anthony Hospital, 608 NW 9th Street, Suite 4100, Oklahoma City, OK 73102, USA. Source: Jamshidi, Mohammad Obermeyer, Robert J Govindaraj, Satish Garcia, Armand Ghani, Abdul J-Okla-State-Med-Assoc. 2002 February; 95(2): 79-80 0030-1876

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Acute pancreatitis-induced hypomagnesemia. Author(s): Department of Internal Medicine, Medical School, University of Ioannina, GR-451 10 Ioannina, Greece.

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Source: Liamis, G Gianoutsos, C Elisaf, M Pancreatology. 2001; 1(1): 74-6 1424-3903 •

Alcoholism and pancreatitis. Source: Korsten, M.A. Alcohol-Health-Res-World-Natl-Inst-Alcohol-Abuse-Alcohol. Washington, D.C. : U.S. Department of Health and Human Services. 1989. volume 13 (3) page 232-237. ill. 0090-838X

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Alcohol-related cirrhosis with pancreatitis. The role of oxidative stress in the progression of the disease. Author(s): Department of Virology and Immunology, Maria Curie-Sklodowska University, Akademicka, Lublin, Poland. Source: Szuster Ciesielska, A Daniluk, J Kandefer Szerszen, M Arch-Immunol-Ther-Exp(Warsz). 2001; 49(2): 139-46 0004-069X

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Anticonvulsant-induced chronic pancreatitis. A case report. Author(s): Servizio di Pronto Soccorso, Ospedale S. Orsola, Bologna, Italy. Source: Pezzilli, R Billi, P Melandri, R Broccoli, P L Fontana, G Ital-J-Gastroenterol. 1992 June; 24(5): 245-6 0392-0623

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Celiac disease and recurrent pancreatitis. Author(s): Department of Gastroenterology and Hepatology, University of Iowa College of Medicine, Iowa City, Iowa, USA. Source: Patel, R S Johlin, F C Murray, J A Gastrointest-Endosc. 1999 December; 50(6): 823-7 0016-5107

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CFTR gene mutations in patients suffering from acute pancreatitis. Author(s): Department of Human Genetics, Medical University, Lublin, Poland. Source: Kostuch, M Rudzki, S Semczuk, A Kulczycki, L Med-Sci-Monit. 2002 September; 8(9): BR369-72 1234-1010

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Changes of plasma levels of gastrointestinal peptides over the course of acute pancreatitis. Any significance for the pathophysiology and treatment of acute pancreatitis? Author(s): 1st Department of Propedeutic Medicine, University of Athens, Medical School, Athens, Greece. Source: Nikou, G C Giamarellos Bourboulis, E J Toumpanakis, C Arnaoutis, T P Kitsou, E Kyriaki, D Katsilambros, N Hepatogastroenterology. 2002 May-June; 49(45): 706-8 0172-6390

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Cholecystokinin fails to promote pancreatic regeneration in diabetic rats following the induction of experimental pancreatitis. Author(s): First Department of Medicine, University of Szeged, H-6701, Szeged, P.O. Box 469, Hungary. [email protected] Source: Takacs, T Hegyi, P Jarmay, K Czako, L Gog, C Rakonczay, Z Jr Nemeth, J Lonovics, J Pharmacol-Res. 2001 Nov; 44(5): 363-72 1043-6618

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Clinical and immunological indicators in patients with chronic pancreatitis and their dynamics in the process of diet therapy. Source: Kiseleva, O.A. Budagovskaia, VolumeN. Voitko, N.E. Vopr-Pitan. Moskva : “Meditsina”. Jan/February 1984. (1) page 21-26. 0042-8833

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Comparison of different endocrine stimulation tests in nondiabetic patients with chronic pancreatitis. Author(s): Department of Medicine, University Hospital Ulm, Germany. Source: von Tirpitz, C Glasbrenner, B Mayer, D Malfertheiner, P Adler, G Hepatogastroenterology. 1998 Jul-August; 45(22): 1111-6 0172-6390

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Current management of necrotizing pancreatitis. Author(s): Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. Source: Clancy, T E Ashley, S W Adv-Surg. 2002; 36: 103-21 0065-3411

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Dietary management of feline pancreatitis. Source: Marks, S.L. Proc-North-Am-Vet-Conf. [Gainesville, Fla.] : Eastern States Veterinary Association, 1992-. 2000. volume 14 page 490-491.

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Diminished lung injury with vascular adhesion molecule-1 blockade in cholinedeficient ethionine diet-induced pancreatitis. Author(s): Department of Surgery, University of Tennessee Health Science Center, 956 Court Avenue, Suite A202, Memphis, TN 38163, USA. Source: Callicutt, C S Sabek, O Fukatsu, K Lundberg, A H Gaber, L Wilcox, H Kotb, M Gaber, A O Surgery. 2003 February; 133(2): 186-96 0039-6060

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Early jejunal nutrition and changes in the immunological parameters of patients with acute pancreatitis. Author(s): Second Department of Surgery, University of Debrecen, Debrecen, Moricz Zs. str. 22., 4004 Debrecen, Hungary. [email protected] Source: Hallay, J Kovacs, G Szatmari, K Bako, A Szentkereszty, Z Lakos, G Sipka, S Sapy, P Hepatogastroenterology. 2001 Sep-October; 48(41): 1488-92 0172-6390

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Effect of a specific synthetic inhibitor of neutrophil elastase (ONO-5046) on the course of acute hemorrhagic pancreatitis in dogs. Author(s): Department of Surgery, National Sendai Hospital, 2-8-8 Miyagino, Miyaginoku, Sendai 983-8520, Japan. Source: Imamura, M Mikami, Y Takahashi, H Yamauchi, H J-Hepatobiliary-PancreatSurg. 1998; 5(4): 422-8 0944-1166

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Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis. Author(s): Department of Gastroenterology, Sao Paulo University Medical School, Rua Maria Jesus de Simoes, 48 Lauzanne Paulista, 02469-010 Sao Paulo SP, Brazil. [email protected] Source: de Souza, L J Sampietre, S N Assis, R S Knowles, C H Leite, K R Jancar, S Monteiro Cunha, J E Machado, M C J-Gastrointest-Surg. 2001 Jul-August; 5(4): 364-70 1091-255X

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Effects of bolus somatostatin in preventing pancreatitis after endoscopic pancreatography: results of a randomized study. Author(s): Gastrointestinal Endoscopy Section, Hospital Clinic I Provincial, University of Barcelona, Spain. Source: Bordas, J M Toledo Pimentel, V Llach, J Elena, M Mondelo, F Gines, A Teres, J Gastrointest-Endosc. 1998 March; 47(3): 230-4 0016-5107

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Effects of octreotide on lipid peroxidation in pancreas and plasma in acute hemorrhagic necrotizing pancreatitis in rats. Author(s): Departments of General, Visceral, Vascular and Thoracic Surgery, Charite Campus Mitte, Humboldt-University of Berlin, Germany. [email protected] Source: Wenger, F A Kilian, M Jacobi, C A Gregor, J I Guski, H Schimke, I Muller, J M Pancreatology. 2002; 2(3): 211-6 1424-3903

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Effects of Tetrandrine and QYT on ICAM-1 and SOD gene expression in pancreas and liver of rats with acute pancreatitis. Author(s): Department of Pathophysiology, Medical College of Tongji University, Shanghai 200331, China. [email protected] Source: Li, Y Y Li, X L Yang, C X Zhong, H Yao, H Zhu, L World-J-Gastroenterol. 2003 January; 9(1): 155-9 1007-9327

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Exocrine pancreatic disease in the dog and cat. 1. Acute pancreatitis. Source: Pidgeon, G. Companion-Anim-Pract. Santa Barbara, Calif. : Veterinary Practice Publishing Co. March 1987. volume 1 (1) page 67, 70-71. 0894-9794

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Fatal pancreatitis associated with valproic acid: review of the literature. Author(s): Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia 19141, USA. Source: Yazdani, K Lippmann, M Gala, I Medicine-(Baltimore). 2002 July; 81(4): 305-10 0025-7974

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Feeding a cat with acute pancreatitis. Author(s): University of Florida, Gainesville, FL. Source: Hill, R. North-American-Veterinary-Conference (USA). (1996). volume 10 page 320-321. cats animal nutrition pancreatitis

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Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial. Author(s): Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. Source: Andriulli, A Clemente, R Solmi, L Terruzzi, V Suriani, R Sigillito, A Leandro, G Leo, P De Maio, G Perri, F Gastrointest-Endosc. 2002 October; 56(4): 488-95 0016-5107

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Hepatic Kupffer cell blockade reduces mortality of acute hemorrhagic pancreatitis in mice. Author(s): Department of Surgery, Sepulveda VA Medical Center, CA, USA. Source: Gloor, B Todd, K E Lane, J S Lewis, M P Reber, H A J-Gastrointest-Surg. 1998 Sep-October; 2(5): 430-5 1091-255X

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Histoprotective effect of antihypoxant olifen during experimental acute pancreatitis. Author(s): I. I. Dzhanelidze St. Petersburg Institute of Ambulance Service. Source: Tolstoi, A D Dzhurko, B I Vashetko, R V Medvedev, Y V Gol'tsov, V R DvoiNovember, V G Zakharova, E V Bull-Exp-Biol-Med. 2001 April; 131(4): 312-4 00074888

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Induction of heat shock proteins fails to produce protection against trypsin-induced acute pancreatitis in rats. Author(s): First Department of Medicine, University of Szeged, Hungary. [email protected] Source: Rakonczay, Z Jr Takacs, T Ivanyi, B Mandi, Y Papai, G Boros, I Varga, I Jost, K Lonovics, J Clin-Exp-Med. 2002 July; 2(2): 89-97 1591-8890

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Influence of somatostatin on acute pancreatitis in rats. Author(s): Department of Surgery, Hopital de la Timone, Marseille, France. Source: Berthet, B Guillou, N Brioche, M I Choux, R Viret, P Ledoray, V Billardon, M Assadourian, R Eur-J-Surg. 1998 October; 164(10): 785-90 1102-4151

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Intracerebroventricular administration of bacterial lipopolysaccharide prevents the development of acute experimental pancreatitis in the rat. Author(s): Physiology, Collegium Medicum, Jagiellonian University Krakow, Poland. Source: Jaworek, J Bonior, J Nawrot, K Leja, A Sendur, R Stachura, J Pawlik, W Konturek, S Med-Sci-Monit. 2002 April; 8(4): BR136-43 1234-1010

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Intraperitoneal free fatty acids induce severe hypocalcemia in rats: a model for the hypocalcemia of pancreatitis. Author(s): Division of Endocrinology, West Haven VA Medical Center, CT 06516. Source: Dettelbach, M A Deftos, L J Stewart, A F J-Bone-Miner-Res. 1990 December; 5(12): 1249-55 0884-0431

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Long term results of lateral pancreaticojejunostomy for chronic alcoholic pancreatitis. Author(s): Department of Digestive Surgery, Hopital Sainte-Marguerite, Marseille, France. Source: Sielezneff, I Malouf, A Salle, E Brunet, C Thirion, X Sastre, B Eur-J-Surg. 2000 January; 166(1): 58-64 1102-4151

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Mechanisms involved in the onset of post-ERCP pancreatitis. Author(s): Department of Internal Medicine and Gastroenterology, Sant'OrsolaM.Malpighi Hospital, University of Bologna, Italy. [email protected] Source: Pezzilli, R Romboli, E Campana, D Corinaldesi, R JOPage 2002 November; 3(6): 162-8 1590-8577

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Morphometric measurements to quantify the cerulein induced hyperstimulatory pancreatitis of rats under the protective effect of lectins. Author(s): Department of Pathology, University of Rostock, Germany. Source: Jonas, L Mikkat, U Witte, A Beckmann, U Dolker, K Weber, H Hahnel, C Kundt, G Nizze, H Anal-Cell-Pathol. 1998; 17(4): 219-30 0921-8912

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Nifedipine for prevention of post-ERCP pancreatitis: a prospective, double-blind randomized study. Author(s): Service des Maladies du Foie et de l'Appareil Digestif, CHU de Bicetre, Le Kremlin-Bicetre, France. Source: Prat, F Amaris, J Ducot, B Bocquentin, M Fritsch, J Choury, A D Pelletier, G Buffet, C Gastrointest-Endosc. 2002 August; 56(2): 202-8 0016-5107

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Nitric oxide, heparin and procaine treatment in experimental ceruleine-induced acute pancreatitis in rats. Author(s): 2nd Department of General, Gastroenterological and Endocrine Surgery, University Medical School, Gdansk, Poland. Source: Dobosz, M Wajda, Z Hac, S Mysliwska, J Bryl, E Mionskowska, L Roszkiewicz, A Mysliwski, A Arch-Immunol-Ther-Exp-(Warsz). 1999; 47(3): 155-60 0004-069X

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Nutrition in patients with acute pancreatitis. Author(s): Department of Surgery, Academic Hospital Maastricht, NL-6202 Maastricht, The Netherlands. [email protected] Source: Dejong, C H Greve, J W Soeters, P B Curr-Opin-Crit-Care. 2001 August; 7(4): 251-6 1070-5295

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Nutritional management of patients with feeding-induced pain: acute pancreatitis. Author(s): Cleveland Clinic Foundation, OH, USA. Source: Seidner, D L Fish, J A Semin-Gastrointest-Dis. 1998 October; 9(4): 200-9 10495118

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Octreotide versus hydrocortisone versus placebo in the prevention of post-ERCP pancreatitis: a multicenter randomized controlled trial. Author(s): 2nd Department of Gastroenterology, Evangelismos General Hospital, University of Athens, Athens, Greece. Source: Manolakopoulos, Spilios Avgerinos, Alec Vlachogiannakos, John Armonis, Anastasios Viazis, Nicolaos Papadimitriou, Nicholas Mathou, Nikoletta Stefanidis,

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Gerasimos Rekoumis, George Vienna, Eleni Tzourmakliotis, Dimitrios Raptis, Sotirios A Gastrointest-Endosc. 2002 April; 55(4): 470-5 0016-5107 •

Oxidative stress in acute pancreatitis. Author(s): Department of Surgery, Otto-von-Guericke-University of Magdeburg, Germany. [email protected] Source: Schulz, H U Niederau, C Klonowski Stumpe, H Halangk, W Luthen, R Lippert, H Hepatogastroenterology. 1999 Sep-October; 46(29): 2736-50 0172-6390

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Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome. Author(s): Department of Surgery, University of South Florida, Tampa 33601, USA. Source: Jaffray, C Yang, J Carter, G Mendez, C Norman, J Surgery. 2000 August; 128(2): 225-31 0039-6060

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Pancreatic head mass: how can we treat it? Acute pancreatitis: conservative treatment. Author(s): Internal Medicine Department, 3rd Division, Cardarelli Hospital. Napoli, Italy. [email protected] Source: Uomo, G JOPage 2000 September; 1(3 Suppl): 130-7 1590-8577

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Pancreatic stone protein of pancreatic calculi in chronic calcified pancreatitis in man. Author(s): Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan. Source: Jin, Chun Xiang Naruse, Satoru Kitagawa, Motoji Ishiguro, Hiroshi Kondo, Takaharu Hayakawa, Shinobu Hayakawa, Tetsuo JOPage 2002 March; 3(2): 54-61 15908577

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Pancreatitis in children on chronic dialysis treated with valproic acid. Author(s): Department of Pediatrics, University of Colorado Medical Center, Denver. Source: Ford, D M Portman, R J Lum, G M Pediatr-Nephrol. 1990 May; 4(3): 259-61 0931041X

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Pathological case of the month: sudden death in a child as a result of pancreatitis during valproic acid therapy. Author(s): Office of the Medical Examiner County of Cook, Chicago, Illinois 60612, USA. Source: Mileusnic, D Donoghue, E R Lifschultz, B D Pediatr-Pathol-Mol-Med. 2002 SepOctober; 21(5): 477-84 1522-7952

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Phosphorus-31 nuclear magnetic resonance spectroscopic study of the canine pancreas: applications to acute alcoholic pancreatitis. Author(s): Department of Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD 21205. Source: Janes, N Clemens, J A Glickson, J D Cameron, J L Adv-Alcohol-Subst-Abuse. 1988; 7(3-4): 213-9 0270-3106

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Predicting and preventing post-ERCP pancreatitis. Author(s): Division of Gastroenterology, Duke University Medical Center, Box 3189, Durham, NC 27710, USA. [email protected] Source: Baillie, John Curr-Gastroenterol-Repage 2002 April; 4(2): 112-9 1522-8037

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Preventive strategies and therapeutic options for hereditary pancreatitis. Author(s): Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, USA. [email protected] Source: Gates, L K Med-Clin-North-Am. 2000 May; 84(3): 589-95 0025-7125

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Prophylactic effect of somatostatin on post-ERCP pancreatitis: a randomized controlled trial. Author(s): Endoscopy Unit, Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China. Source: Poon, R T Yeung, C Lo, C M Yuen, W K Liu, C L Fan, S T Gastrointest-Endosc. 1999 May; 49(5): 593-8 0016-5107

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Role of enteral nutrition in the pathophysiology and treatment of pancreatitis and cystic fibrosis. Author(s): Pancreas Center, Beth Israel Deaconess Medical Center, Boston, Mass., USA. Source: Freedman, S D Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 2000; 3: 239-43; discussion 243-6 1422-7584

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Role of S-adenosylmethionine in two experimental models of pancreatitis. Author(s): Division of Gastroenterology and Liver Diseases, USC Liver Disease Research Center, Keck School of Medicine USC, Los Angeles, California 90033, USA. [email protected] Source: Lu, S C Gukovsky, I Lugea, A Reyes, C N Huang, Z Z Chen, L Mato, J M Bottiglieri, T Pandol, S J FASEB-J. 2003 January; 17(1): 56-8 1530-6860

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Secondary pancreatic involvement by diffuse large B-cell lymphoma presenting as acute pancreatitis: treatment and outcome. Author(s): Department of Gastroenterology and Hepatology, Henry Mondor University Hospital, Creteil, France. Source: Bernardeau, M Auroux, J Cavicchi, M Haioun, C Tsakiris, L Delchier, J C Pancreatology. 2002; 2(4): 427-30 1424-3903

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Severe acute pancreatitis: treatment with somatostatin. Author(s): Intensive Care Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. Source: Planas, M Perez, A Iglesia, R Porta, I Masclans, J R Bermejo, B Intensive-CareMed. 1998 January; 24(1): 37-9 0342-4642

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Somatostatin and octreotide in acute pancreatitis: the never-ending story. Author(s): Department of Surgical and Gastroenterological Sciences, University of Verona, Italy. Source: Cavallini, G Frulloni, L Dig-Liver-Dis. 2001 March; 33(2): 192-201

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Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice. Author(s): Departments of Surgery and Physiology, University of California School of Medicine, San Francisco 94143-0790, USA. Source: Maa, J Grady, E F Yoshimi, S K Drasin, T E Kim, E H Hutter, M M Bunnett, N W Kirkwood, K S Surgery. 2000 August; 128(2): 232-9 0039-6060

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Temporal correlation of tumor necrosis factor-alpha release, upregulation of pulmonary ICAM-1 and VCAM-1, neutrophil sequestration, and lung injury in dietinduced pancreatitis. Author(s): Department of Surgery, University of Tennessee-Memphis, 38163, USA. Source: Lundberg, A H Granger, N Russell, J Callicutt, S Gaber, L W Kotb, M Sabek, O Gaber, A O J-Gastrointest-Surg. 2000 May-June; 4(3): 248-57 1091-255X

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The effects of prostaglandin E1 on the microperfusion of the pancreas during acute necrotizing pancreatitis in rats. Author(s): Department of Surgery, Karadeniz Technical University, Trabzon, Turkey.

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Source: Yucel, K Alhan, E Kucuktulu, U Piri, M Ercin, Hepatogastroenterology. 2002 Mar-April; 49(44): 544-8 0172-6390

C

Deger,

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The influence of nifedipine (calcium channel blocker) and Bay-K-8644 (calcium channel agonist) on the development of experimental acute pancreatitis. Author(s): Dept. of Gastroenterology, Medical University of Lublin. Source: Slomka, M Celinski, K Wargocki, J Kleinrok, Z Czerny, K Cichoz Lach, H AnnUniv-Mariae-Curie-Sklodowska-[Med]. 2001; 56: 29-34 0066-2240

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The time course of liver DNA and RNA alterations in acute experimental pancreatitis in rats--a possible mechanism of prostacyclin (PGI2) protection. Author(s): Gastroenterology Department, Medical Academy, Bialystok, Poland. Source: Jurkowska, G Dlugosz, J Gabryelewicz, A Andrzejewska, A Hepatogastroenterology. 1989 August; 36(4): 249-54 0172-6390

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Thyroid function in acute pancreatitis. Author(s): Department of Digestive Medicine, Costa del Sol Hospital, Marbella, Malaga, Spain. Source: De Sola, C Redondo, M Pallares, F Redondo, E Hortas, M L Morell, M Rev-EspEnferm-Dig. 1998 January; 90(1): 15-22 1130-0108

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Vitamins Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com

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Minerals Magnesium Source: Healthnotes, Inc.; www.healthnotes.com

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Food and Diet Beef Source: Healthnotes, Inc.; www.healthnotes.com High-Fiber Diet Source: Healthnotes, Inc.; www.healthnotes.com Kiwi Source: Healthnotes, Inc.; www.healthnotes.com

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

A case of paclitaxel-induced pancreatitis. Author(s): Kumar DM, Sundar S, Vasanthan S. Source: Clin Oncol (R Coll Radiol). 2003 February; 15(1): 35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602552&dopt=Abstract

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A randomized double-blind study using CaNa2EDTA, a phospholipase A2 inhibitor, in the management of human acute pancreatitis. Author(s): Tykka HT, Vaittinen EJ, Mahlberg KL, Railo JE, Pantzar PJ, Sarna S, Tallberg T. Source: Scandinavian Journal of Gastroenterology. 1985 January; 20(1): 5-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3922048&dopt=Abstract

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Acetaminophen induced pancreatitis. Author(s): Mofenson HC, Caraccio TR, Nawaz H, Steckler G.

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Source: Journal of Toxicology. Clinical Toxicology. 1991; 29(2): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1675695&dopt=Abstract •

Acupuncture and transcutaneous electric nerve stimulation in the treatment of pain associated with chronic pancreatitis. A randomized study. Author(s): Ballegaard S, Christophersen SJ, Dawids SG, Hesse J, Olsen NV. Source: Scandinavian Journal of Gastroenterology. 1985 December; 20(10): 1249-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3912961&dopt=Abstract

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Acute haemorrhagic pancreatitis following L-asparaginase therapy in acute lymphoblastic leukaemia --a case report. Author(s): Tan CL, Chiang SP, Wee KP. Source: Singapore Med J. 1974 December; 15(4): 278-82. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4533158&dopt=Abstract

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Acute pancreatitis associated with administration of a nitric oxide synthase inhibitor in tumor-bearing dogs. Author(s): Poulson JM, Dewhirst MW, Gaskin AA, Vujaskovic Z, Samulski TV, Prescott DM, Meyer RE, Page RL, Thrall DE. Source: In Vivo. 2000 November-December; 14(6): 709-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204486&dopt=Abstract

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Acute pancreatitis associated with chemotherapy for germ cell tumors in two patients. Author(s): Socinski MA, Garnick MB. Source: Annals of Internal Medicine. 1988 April; 108(4): 567-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2450502&dopt=Abstract

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Acute pancreatitis induced by diffuse pancreatic invasion of adult T-cell leukemia/lymphoma cells. Author(s): Mori A, Kikuchi Y, Motoori S, Watanabe J, Shinozaki M, Eguchi M. Source: Digestive Diseases and Sciences. 2003 October; 48(10): 1979-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627344&dopt=Abstract

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Alexithymic features of the patients with chronic pancreatitis. Author(s): Nakai Y, Sugita M, Nakagawa T, Araki T, Ikemi Y. Source: Psychotherapy and Psychosomatics. 1979; 31(1-4): 205-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=482541&dopt=Abstract

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Alterations in intestinal function in acute pancreatitis in an experimental model. Author(s): Wang XD, Wang Q, Andersson R, Ihse I.

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Source: The British Journal of Surgery. 1996 November; 83(11): 1537-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9026331&dopt=Abstract •

Analysis of occluded pancreatic stents and juices in patients with chronic pancreatitis. Author(s): Smits ME, Groen AK, Mok KS, van Marle J, Tytgat GN, Huibregtse K. Source: Gastrointestinal Endoscopy. 1997 January; 45(1): 52-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9013170&dopt=Abstract

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Antifibrotic effect of the herbal medicine Saiko-keishi-to (TJ-10) on chronic pancreatitis in the WBN/Kob rat. Author(s): Su SB, Motoo Y, Xie MJ, Taga H, Sawabu N. Source: Pancreas. 2001 January; 22(1): 8-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11138977&dopt=Abstract

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Antioxidant treatment in hereditary pancreatitis. A pilot study on three young patients. Author(s): Uomo G, Talamini G, Rabitti PG. Source: Dig Liver Dis. 2001 January-February; 33(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303976&dopt=Abstract

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Aprotinin and Na2CaEDTA in experimental hemorrhagic pancreatitis in pigs. Author(s): Puolakkainen P, Paananen A, Kaarne M, Kuusi T, Lempinen M, Schroder T. Source: Scandinavian Journal of Gastroenterology. 1987 January; 22(1): 35-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2436280&dopt=Abstract

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Autoimmune pancreatitis with F-18 fluoro-2-deoxy-D-glucose PET findings Author(s): Nakamoto Y, Sakahara H, Higashi T, Saga T, Sato N, Okazaki K, Imamura M, Konishi J. Source: Clinical Nuclear Medicine. 1999 October; 24(10): 778-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512104&dopt=Abstract

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Beneficial effect of a soy flour diet in chronic pancreatitis. Author(s): Pap A, Berger Z, Varro V. Source: The Mount Sinai Journal of Medicine, New York. 1983 May-June; 50(3): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6312297&dopt=Abstract

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Beneficial effects of a novel IH636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis. Author(s): Banerjee B, Bagchi D.

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Source: Digestion. 2001; 63(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351148&dopt=Abstract •

Cerulein-induced acute pancreatitis in the rat is significantly ameliorated by treatment with MEK1/2 inhibitors U0126 and PD98059. Author(s): Clemons AP, Holstein DM, Galli A, Saunders C. Source: Pancreas. 2002 October; 25(3): 251-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370536&dopt=Abstract

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Cholecystokinin cleavage to cholecystokinin-octapeptide in vivo and in vitro: accelerated cleavage in acute pancreatitis. Author(s): Springer CJ, Calam J. Source: Gastroenterology. 1988 July; 95(1): 143-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2453390&dopt=Abstract

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Complementary effect of cholecystokinin-octapeptide and soy flour treatment in chronic pancreatitis. Author(s): Pap A, Berger Z, Varro V. Source: The Mount Sinai Journal of Medicine, New York. 1984 June; 51(3): 254-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6087129&dopt=Abstract

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Comprehensive treatment of acute hemorrhagic pancreatitis. Author(s): Nugent FW, Atendido WA, Gibb SP. Source: The American Journal of Gastroenterology. 1967 June; 47(6): 511-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4292673&dopt=Abstract

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Controlled trial of high-dose octreotide in treatment of acute pancreatitis. Evidence of improvement in disease severity. Author(s): Beechey-Newman N. Source: Digestive Diseases and Sciences. 1993 April; 38(4): 644-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8462363&dopt=Abstract

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Current concepts in the management of pancreatitis. Author(s): Wilson C, Imrie CW. Source: Drugs. 1991 March; 41(3): 358-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1711443&dopt=Abstract

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Cytostatics in the treatment of chronic and acute pancreatitis. Author(s): Popiela T, Turczynowski W, Zajac A. Source: Hepatogastroenterology. 1980 October; 27(5): 390-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7009361&dopt=Abstract

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Diabetes mellitus and pancreatitis as a complication of L-asparaginase therapy. Author(s): Charan VD, Desai N, Singh AP, Choudhry VP. Source: Indian Pediatrics. 1993 June; 30(6): 809-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8132268&dopt=Abstract

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Dietary antioxidants and chronic pancreatitis. Author(s): Rose P, Fraine E, Hunt LP, Acheson DW, Braganza JM. Source: Hum Nutr Clin Nutr. 1986 March; 40(2): 151-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3957720&dopt=Abstract

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Duodenoscopy in treatment of acute gallstone pancreatitis. Author(s): Zhou MQ, Li NP, Lu RD. Source: Hepatobiliary Pancreat Dis Int. 2002 November; 1(4): 608-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607696&dopt=Abstract

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Effect of herbal medicine Saiko-keishi-to (TJ-10) on rat spontaneous chronic pancreatitis: comparison with other herbal medicines. Author(s): Motoo Y, Su SB, Xie MJ, Taga H, Sawabu N. Source: International Journal of Pancreatology : Official Journal of the International Association of Pancreatology. 2000 April; 27(2): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10862511&dopt=Abstract

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Effect of osteopathic manipulative treatment of length of stay for pancreatitis: a randomized pilot study. Author(s): Radjieski JM, Lumley MA, Cantieri MS. Source: J Am Osteopath Assoc. 1998 May; 98(5): 264-72. Erratum In: J Am Osteopath Assoc 1998 July; 98(7): 408. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9615558&dopt=Abstract

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Effect of the microtubule-disrupting drug colchicine on rat cerulein-induced pancreatitis in comparison with the microtubule stabilizer taxol. Author(s): Ueda T, Takeyama Y, Adachi M, Toyokawa A, Kishida S, Yamamoto M, Saitoh Y. Source: Pancreas. 1995 October; 11(3): 294-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8577685&dopt=Abstract

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Effects of green tea catechins (Polyphenon 100) on cerulein-induced acute pancreatitis in rats. Author(s): Takabayashi F, Harada N. Source: Pancreas. 1997 April; 14(3): 276-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9094158&dopt=Abstract

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Effects of Tetrandrine and QYT on ICAM-1 and SOD gene expression in pancreas and liver of rats with acute pancreatitis. Author(s): Li YY, Li XL, Yang CX, Zhong H, Yao H, Zhu L. Source: World Journal of Gastroenterology : Wjg. 2003 January; 9(1): 155-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508373&dopt=Abstract

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Electrical stimulation of the celiac plexus for pain relief in chronic pancreatitis. A clinical note. Author(s): Srikantha K, Choi JJ, Wu WH. Source: Acupuncture & Electro-Therapeutics Research. 1986; 11(2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2879414&dopt=Abstract

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Emblica officinalis: a novel therapy for acute pancreatitis--an experimental study. Author(s): Thorat SP, Rege NN, Naik AS, Thatte UM, Joshi A, Panicker KN, Bapat RD, Dahanukar SA. Source: Hpb Surg. 1995; 9(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8857450&dopt=Abstract

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Enhancement of pancreas and diagnosis of pancreatitis using manganese dipyridoxyl diphosphate. Author(s): Baba Y, Lerch MM, Tanimoto A, Kreft BP, Saluja AK, Zhao L, Chen J, Steer ML, Stark DD. Source: Investigative Radiology. 1994 June; 29 Suppl 2: S300-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7928263&dopt=Abstract

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Enterokinase induced pancreatitis: its prevention with Trasylol and soybean trypsin inhibitor. Author(s): Mann NS, Kadian RS, Narenderan K. Source: Am J Proctol Gastroenterol Colon Rectal Surg. 1978 November-December; 29(6): 13-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=316652&dopt=Abstract

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Expression of pancreatitis-associated protein (PAP) in rat spontaneous chronic pancreatitis: effect of herbal medicine Saiko-keishi-to (TJ-10). Author(s): Su SB, Motoo Y, Xie MJ, Sakai J, Taga H, Sawabu N. Source: Pancreas. 1999 October; 19(3): 239-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10505754&dopt=Abstract

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FDG-PET of autoimmune-related pancreatitis: preliminary results. Author(s): Nakamoto Y, Saga T, Ishimori T, Higashi T, Mamede M, Okazaki K, Imamura M, Sakahara H, Konishi J.

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Source: European Journal of Nuclear Medicine. 2000 December; 27(12): 1835-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11189947&dopt=Abstract •

Foreign serum-induced pancreatitis in mice. I. A new model of acute pancreatitis. Author(s): Janigan DT, Nevalainen TJ, MacAulay MA, Vethamany VG. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1975 December; 33(6): 591-607. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1202281&dopt=Abstract

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Formalized therapeutic guideline for hyperlipidemic severe acute pancreatitis. Author(s): Mao EQ, Tang YQ, Zhang SD. Source: World Journal of Gastroenterology : Wjg. 2003 November; 9(11): 2622-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606112&dopt=Abstract

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Hereditary pancreatitis-associated mutation asn(21) --> ile stabilizes rat trypsinogen in vitro. Author(s): Sahin-Toth M. Source: The Journal of Biological Chemistry. 1999 October 15; 274(42): 29699-704. Erratum In: J Biol Chem 2000 May 5; 275(18): 14004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10514442&dopt=Abstract

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High dose octreotide in the management of acute pancreatitis. Author(s): Karakoyunlar O, Sivrel E, Tanir N, Denecli AG. Source: Hepatogastroenterology. 1999 May-June; 46(27): 1968-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430379&dopt=Abstract

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Hyperbaric oxygen therapy attenuates pancreatic microcirculatory derangement and lung edema in an acute experimental pancreatitis model in rats. Author(s): Chen HM, Shyr MH, Ueng SW, Chen MF. Source: Pancreas. 1998 July; 17(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9667519&dopt=Abstract

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Hyperbaric oxygen therapy in the treatment of refractory peripancreatic abscess associated with severe acute pancreatitis. Author(s): Izawa K, Tsunoda T, Ura K, Yamaguchi T, Ito T, Kanematsu T, Tsuchiya R. Source: Gastroenterol Jpn. 1993 April; 28(2): 284-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8486216&dopt=Abstract

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Hyperbaric oxygen, allopurinol, and diet-induced acute pancreatitis. Author(s): Degertekin H, Ertan A, Yater RD, Van Meter K, Akdamar K.

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Source: Annals of Internal Medicine. 1985 September; 103(3): 474-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4026099&dopt=Abstract •

Induction of apoptosis reduces the severity of caerulein-induced pancreatitis in mice. Author(s): Saluja A, Hofbauer B, Yamaguchi Y, Yamanaka K, Steer M. Source: Biochemical and Biophysical Research Communications. 1996 March 27; 220(3): 875-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8607859&dopt=Abstract

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Induction of apoptosis with an extract of Artemisia asiatica attenuates the severity of cerulein-induced pancreatitis in rats. Author(s): Hahm KB, Kim JH, You BM, Kim YS, Cho SW, Yim H, Ahn BO, Kim WB. Source: Pancreas. 1998 August; 17(2): 153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700946&dopt=Abstract

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Is there a place for pancreatic enzymes in the treatment of pain in chronic pancreatitis? Author(s): Mossner J. Source: Digestion. 1993; 54 Suppl 2: 35-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7693533&dopt=Abstract

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Issues in hyperlipidemic pancreatitis. Author(s): Yadav D, Pitchumoni CS. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 54-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488710&dopt=Abstract

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Lack of association between cassava consumption and tropical pancreatitis syndrome. Author(s): Narendranathan M, Cheriyan A. Source: Journal of Gastroenterology and Hepatology. 1994 May-June; 9(3): 282-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8054529&dopt=Abstract

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Letter 1: Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis (Br J Surg 2002; 89: 11031107). Author(s): Weale R, Edwards A. Source: The British Journal of Surgery. 2003 January; 90(1): 122-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520591&dopt=Abstract

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Lymphoma-associated pancreatitis as a presenting manifestation of immunoblastic lymphoma. Author(s): Safadi R, Or R, Bar Ziv J, Polliack A.

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Source: Leukemia & Lymphoma. 1994 January; 12(3-4): 317-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7513221&dopt=Abstract •

Lysolecithin concentration in pancreatic tissue during therapy with phospholipase A2-inhibitors in acute necrotizing pancreatitis. Author(s): Kahle M, Konig H, Filler RD. Source: Klin Wochenschr. 1989 February 1; 67(3): 177-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2494378&dopt=Abstract

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Mechanisms of Chinese herb emodin and somatostatin analogs on pancreatic regeneration in acute pancreatitis in rats. Author(s): Gong Z, Yuan Y, Lou K, Tu S, Zhai Z, Xu J. Source: Pancreas. 2002 August; 25(2): 154-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142738&dopt=Abstract

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Mutations in the lipoprotein lipase gene as a cause of hypertriglyceridemia and pancreatitis in taiwan. Author(s): Jap TS, Jenq SF, Wu YC, Chiu CY, Cheng HM. Source: Pancreas. 2003 August; 27(2): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883259&dopt=Abstract

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No effect of long-term treatment with pancreatic extract on recurrent abdominal pain in patients with chronic pancreatitis. Author(s): Malesci A, Gaia E, Fioretta A, Bocchia P, Ciravegna G, Cantor P, Vantini I. Source: Scandinavian Journal of Gastroenterology. 1995 April; 30(4): 392-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7610357&dopt=Abstract

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Nutrition supplementation in patients with acute and chronic pancreatitis. Author(s): Scolapio JS, Malhi-Chowla N, Ukleja A. Source: Gastroenterology Clinics of North America. 1999 September; 28(3): 695-707. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10503145&dopt=Abstract

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Omega-3 fatty acid supplementation increases anti-inflammatory cytokines and attenuates systemic disease sequelae in experimental pancreatitis. Author(s): Foitzik T, Eibl G, Schneider P, Wenger FA, Jacobi CA, Buhr HJ. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2002 November-December; 26(6): 351-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405646&dopt=Abstract

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Organic matrix of pancreatic stones associated with nutritional pancreatitis. Author(s): Montalto G, Multigner L, Sarles H, De Caro A.

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Source: Pancreas. 1988; 3(3): 263-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3387420&dopt=Abstract •

Paclitaxel-induced pancreatitis: a case report. Author(s): Hoff PM, Valero V, Holmes FA, Whealin H, Hudis C, Hortobagyi GN. Source: Journal of the National Cancer Institute. 1997 January 1; 89(1): 91-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8978416&dopt=Abstract

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Pancreatic microvascular permeability in caerulein-induced acute pancreatitis. Author(s): Sweiry JH, Mann GE. Source: The American Journal of Physiology. 1991 October; 261(4 Pt 1): G685-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1928354&dopt=Abstract

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Pancreatitis and intravenous fat: an association in patients with inflammatory bowel disease. Author(s): Noseworthy J, Colodny AH, Eraklis AJ. Source: Journal of Pediatric Surgery. 1983 June; 18(3): 269-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6410038&dopt=Abstract

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Pancreatitis and pulmonary hemorrhage complicating closed-chest cardiac massage. Author(s): Cowan D. Source: Can Med Assoc J. 1966 November 5; 95(19): 976-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5922913&dopt=Abstract

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Pancreatitis and the lungs. Author(s): McWilliams H, Gross R. Source: The American Surgeon. 1974 August; 40(8): 448-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4602093&dopt=Abstract

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Pancreatitis during combination chemotherapy. Author(s): Newman CE, Ellis DJ. Source: Clin Oncol. 1979 March; 5(1): 83-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=421389&dopt=Abstract

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Pancreatitis following ingestion of a homeopathic preparation. Author(s): Kerr HD, Yarborough GW. Source: The New England Journal of Medicine. 1986 June 19; 314(25): 1642-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3713765&dopt=Abstract

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Pancreatitis Partners: a sharing and educational support group. Author(s): Shepp PH, Chase P, Rawls E.

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Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 1999 July-August; 22(4): 155-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10745743&dopt=Abstract •

Pathological events in experimental acute pancreatitis prevented by the bradykinin antagonist, Hoe 140. Author(s): Griesbacher T, Tiran B, Lembeck F. Source: British Journal of Pharmacology. 1993 February; 108(2): 405-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8448591&dopt=Abstract

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Phospholipase A2 inhibitors and their possible clinical use in the treatment of acute pancreatitis. Author(s): Tykka H, Mahlberg K, Pantzar P, Tallberg T. Source: Scandinavian Journal of Gastroenterology. 1980; 15(5): 519-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6777862&dopt=Abstract

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Phospholipase activity in pancreatic exudate in experimental acute pancreatitis. Author(s): Gjone E, Ofstad E, Marton PF, Amundsen E. Source: Scandinavian Journal of Gastroenterology. 1967; 2(3): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4963682&dopt=Abstract

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Possible drug-associated pancreatitis after paclitaxel-cremophor administration. Author(s): Mills KM, Johnson DM, Middlebrooks M, Burton GV. Source: Pharmacotherapy. 2000 January; 20(1): 95-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641981&dopt=Abstract

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Protective effect of a microtubule stabilizer taxol on caerulein-induced acute pancreatitis in rat. Author(s): Ueda T, Takeyama Y, Kaneda K, Adachi M, Ohyanagi H, Saitoh Y. Source: The Journal of Clinical Investigation. 1992 January; 89(1): 234-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1370296&dopt=Abstract

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Re: Vinorelbine-induced pancreatitis: a case report. Author(s): Raderer M, Kornek G, Scheithauer W. Source: Journal of the National Cancer Institute. 1998 February 18; 90(4): 329. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9486821&dopt=Abstract

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Secondary pancreatic involvement by diffuse large B-cell lymphoma presenting as acute pancreatitis: treatment and outcome. Author(s): Bernardeau M, Auroux J, Cavicchi M, Haioun C, Tsakiris L, Delchier JC.

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Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2002; 2(4): 427-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138234&dopt=Abstract •

Severe hypertriglyceridemia and pancreatitis when estrogen replacement therapy is given to hypertriglyceridemic women. Author(s): Glueck CJ, Lang J, Hamer T, Tracy T. Source: The Journal of Laboratory and Clinical Medicine. 1994 January; 123(1): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8288962&dopt=Abstract

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Soybean trypsin inhibitor and cerulein accelerate recovery of cerulein-induced pancreatitis in rats. Author(s): Jurkowska G, Grondin G, Masse S, Morisset J. Source: Gastroenterology. 1992 February; 102(2): 550-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1370663&dopt=Abstract

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The effect of hyperbaric oxygen treatment on oxidative stress in experimental acute necrotizing pancreatitis. Author(s): Yasar M, Yildiz S, Mas R, Dundar K, Yildirim A, Korkmaz A, Akay C, Kaymakcioglu N, Ozisik T, Sen D. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2003; 52(1): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625815&dopt=Abstract

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The effect of microtubule stabilizer on rat caerulein-induced pancreatitis. Author(s): Ueda T. Source: The Kobe Journal of Medical Sciences. 1991 April; 37(2): 97-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1717741&dopt=Abstract

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The effects of free oxygen radical scavenger and platelet-activating factor antagonist agents in experimental acute pancreatitis. Author(s): Soybir G, Koksoy F, Ekiz F, Yalcin O, Fincan K, Haklar G, Yuksel M. Source: Pancreas. 1999 August; 19(2): 143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10438161&dopt=Abstract

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The effects of green tea catechins (Polyphenon) on DL-ethionine-induced acute pancreatitis. Author(s): Takabayashi F, Harada N, Hara Y. Source: Pancreas. 1995 August; 11(2): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7479668&dopt=Abstract

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Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms.

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Author(s): Du WD, Yuan ZR, Sun J, Tang JX, Cheng AQ, Shen DM, Huang CJ, Song XH, Yu XF, Zheng SB. Source: World Journal of Gastroenterology : Wjg. 2003 November; 9(11): 2565-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606098&dopt=Abstract •

Transcutaneous electrical nerve stimulation in the management of pancreatitis pain. Author(s): Roberts HJ. Source: Southern Medical Journal. 1978 April; 71(4): 396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=76340&dopt=Abstract

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Treatment of acute pancreatitis with liyi tang--a report of 50 cases. Author(s): Chen Q, Lu J. Source: J Tradit Chin Med. 1997 December; 17(4): 250-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437205&dopt=Abstract

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Treatment of late allograft pancreatitis with oral pancreatic extract. Author(s): Garvin PJ, Lindsey L, Aridge DL, Burton FR, Patel BK, George E, Reese J. Source: Transplantation. 1991 October; 52(4): 733-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1926355&dopt=Abstract

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Use of a synthetic protease inhibitor for the treatment of L-asparaginase-induced acute pancreatitis complicated by disseminated intravascular coagulation. Author(s): Murakawa M, Okamura T, Shibuya T, Harada M, Otsuka T, Niho Y. Source: Annals of Hematology. 1992 May; 64(5): 249-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1623061&dopt=Abstract

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Vinorelbine-induced pancreatitis: a case report. Author(s): Tester W, Forbes W, Leighton J. Source: Journal of the National Cancer Institute. 1997 November 5; 89(21): 1631. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9362167&dopt=Abstract

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Wilson's disease associated with pancreatitis. Author(s): Weizman Z, Picard E, Barki Y, Moses S. Source: Journal of Pediatric Gastroenterology and Nutrition. 1988 November-December; 7(6): 931-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3199280&dopt=Abstract

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Zinc in mononuclear leucocytes in alcoholics with liver cirrhosis or chronic pancreatitis and in patients with Crohn's disease before and after zinc supplementation. Author(s): Bro S, Stokholm M, Jorgensen PJ.

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Source: J Trace Elem Electrolytes Health Dis. 1989 December; 3(4): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2535348&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to pancreatitis; 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 Celiac Disease Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Triglycerides Source: Healthnotes, Inc.; www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com

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Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Malabsorption Source: Healthnotes, Inc.; www.healthnotes.com Morning Sickness Source: Healthnotes, Inc.; www.healthnotes.com Mumps Source: Integrative Medicine Communications; www.drkoop.com Pancreatic Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com •

Herbs and Supplements Digestive Enzymes Source: Healthnotes, Inc.; www.healthnotes.com Lipase Source: Healthnotes, Inc.; www.healthnotes.com Medium-Chain Triglycerides Source: Prima Communications, Inc.www.personalhealthzone.com Methionine Source: Healthnotes, Inc.; www.healthnotes.com

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

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

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

A Randomized Controlled Trial and Cost Effectiveness Analysis of Parenteral Nutrition and Enteral Nutrition in Severe Pancreatitis: A Model for Health Technology Assessment by Louie, Brian Edward; Mph from University of Alberta (Canada), 2002, 114 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69674

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Antioxidants, Nitric Oxide and Chronic Pancreatitis by Fredstrom, Susan Beth; PhD from University of Minnesota, 2002, 220 pages http://wwwlib.umi.com/dissertations/fullcit/3047627

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The Bile Factor in Experimental Pancreatitis by Poncelet, Paul; PhD from McGill University (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15967

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The Role of Cyclooxygenase-2 (COX-2) in Acute Pancreatitis by Ethridge, Richard Thomas; PhD from The University of Texas Graduate Sch. of Biomedical Sci. at Galveston, 2003, 108 pages http://wwwlib.umi.com/dissertations/fullcit/3083540

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The Role of Proelastase-Elastase Enzyme in the Pathogenesis of Experimental Pancreatitis by Geokas, Michael C; AdvDeg from McGill University (Canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK00450

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

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

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

A study to determine if antibiotics prevent infection in the pancreas of patients where part of the pancreas has died. Condition(s): Pancreatitis, Acute Necrotizing Study Status: This study is currently recruiting patients. Sponsor(s): AstraZeneca Purpose - Excerpt: This is a research study in patients having a condition known as necrotizing pancreatitis. This is inflammation of the pancreas (an intestinal organ which assists with digestion) that has resulted in the damage and death of some pancreatic tissue. This damaged pancreatic tissue may develop a bacterial infection, which can cause further -sometimes very serious- health problems. It may be possible to prevent or delay infection by giving 'prophylactic' antibiotics (that is - to provide protection before any infection starts). However, it is not certain that this antibiotic therapy will be successful. This study is being carried out to see whether the antibiotic 'Meropenem' (which is also known as MERREM I.V.) provides protection from developing a pancreatic infection. This will be done by comparing the progress of patients who receive meropenem with those who receive a non-active placebo solution (a solution that does not contain any active medication). Meropenem or placebo would be given in addition to the standard treatment received for pancreatitis. It is not known if meropenem will help prevent infections associated with necrotizing pancreatitis. Approximately 240 patients will take part in this study. Study participation will be

8

These are listed at www.ClinicalTrials.gov.

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carried out for up to 6 weeks, and patients will receive the study treatment up to a maximum of 21 days. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061438 •

Genetic Linkage Study for Hereditary Pancreatitis Condition(s): Pancreatitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Pittsburgh Purpose - Excerpt: Objectives: I. Establish linkage in families with hereditary pancreatitis between the phenotype and a chromosomal locus (loci) that contains the responsible gene. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004475

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Videoscopic Drainage of Infected Pancreatic Collections Condition(s): Pancreatitis, Acute Necrotizing Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The VARD (Videoendoscopic Assisted Retroperitoneal Drainage) approach as treatment for necrotizing pancreatitis proposes an alternative to standard complicated open abdomen treatment methods. This treatment involves making a small incision and looking inside the abdomen with a videoendoscope. A videoendoscope is an instrument with a small camera and light on the end. It also has an extension tool that the surgeon can use to clean out any dead and infected tissue in the abdomen. This approach may reveal a treatment opportunity with faster recovery potential and shorter hospitalizations for patients with necrotizing pancreatitis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061269

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Safety and efficacy study of IL-10 (Tenovil TM) in the prevention of Post-ERCP Acute Pancreatitis Condition(s): Bile Duct Diseases; Biliary Tract Diseases; Gallbladder Diseases; Pancreatitis; Pancreatic Diseases Study Status: This study is terminated. Sponsor(s): Schering-Plough

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Purpose - Excerpt: The purpose of this study is to determine if a single dose of IL-10 compared to placebo is safe and effective in reducing the incidence of post-ERCP acute pancreatitis for subjects with increased risk. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040131

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Patents on Pancreatitis By performing a patent search focusing on pancreatitis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on pancreatitis: •

Antibodies specific for human pancreatitis associated protein Inventor(s): Dagorn; Jean-Charles (Marseille, FR), Iovanna; Juan-Lucio (Marseille, FR), Keim; Volker (Heddesheim, DE) Assignee(s): Institut National de la Santa et de la Recherche Medicale (Paris Cedex, FR) Patent Number: 5,959,086 Date filed: April 14, 1995 Abstract: The invention relates to the family of the protein (PAP) associated with acute pancreatitis in man and in the rat. It also relates to the nucleotide fragments coding for the above proteins. Also included in the framework of the invention are antibodies which recognize the PAP and which are capable of being used for the purpose of diagnosing pancreatitis. The invention also relates to the production of the PAP, in particular by genetic engineering. Excerpt(s): The present invention relates to proteins associated with acute pancreatitis and agents for the diagnosis of this disease. Acute pancreatitis is an inflammatory disease of the pancreas which, pathologically speaking, extends from the simple edematous form to the complete hemorrhagic necrosis of the gland. Necro-hemorrhagic pancreatitis is a very serious disease since, depending on the authors, its mortality is estimated to vary from 30 to 70%. In certain cases it is very difficult to establish the diagnosis of acute pancreatitis with certainty (Sarner, M. et al, Gastroenterol. (1984), 13: 865-870). This diagnosis is based in particular on clinical examination (acute abdominal pain), on the determination of a certain number of substances in the plasma or in the peritoneal fluid (Bradley, J. et al., Br. J. Surg. (1981), 68: 245-246; and Dubick, M. et al., Dig. Dis. Sci. (1987), 32: 305-312). The analytical determinations employed include those for amylase, lipase, trypsin, elastase, ribonuclease, phospholipase A2,.alpha.-2 macroglobulin, calcium, LDH, protease inhibitors and others. However, none of them has proved to be specific, practical or above all, discriminating. Hence, it is usually considered sufficient to determine amylasemia. Recently, ultrasonography and computerized tomography have appeared to be able to facilitate the diagnosis of pancreatitis without, however, decisive progress being made (Silverstein, W. et al., Am. J. Roentgenol., (1981), 137: 497-502). In 1984, Keim et al. published (Digestion, (1984), 29: 242-249) results of the consequences of cannulation of the pancreatic duct and the induction of pancreatitis on the protein composition of the pancreatic juice in the rat, this animal being used an experimental model. After the operation of cannulation (1 to 2 days later), the authors observed a fall in the level of amylase in the pancreatic juice followed, 3 to 4 days after the operation, by a return to the normal amylase level. Web site: http://www.delphion.com/details?pn=US05959086__

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Apparatus and method for abdomino-pelvic chemotherapy perfusion and lavage Inventor(s): Sugarbaker; Paul H. (3629 Fulton St., NW., Washington, DC 20007) Assignee(s): none reported Patent Number: 6,383,162 Date filed: November 12, 1999

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Abstract: An abdomino-pelvic perfusion and lavage apparatus is disclosed to which skin surrounding an incision formed through an abdominal wall of a patient can be attached and suspended. The apparatus includes a containment vessel impermeable to water and air, having a wall having a base, wherein the wall has an upper end with a perimeter which defines an upper opening, a lower end with a perimeter which defines a base opening, a cranial end with a perimeter edge which defines an opening, and a caudal end with a perimeter edge which defines an opening. The containment vessel can be carried by a table on which a patient is positioned. Scaffolding carried by the containment vessel supports and elevates the skin surrounding the incision made through the abdominal wall of the patient and thereby forms a well above, and extending into, an abdomino-pelvic cavity. A plurality of fluid ports communicate through the wall of the containment vessel. The cranial opening and the caudal opening can be sealed around the patient's torso. A base seal can seal the base of the containment vessel to the table. Perfusion fluid can be supplied from a reservoir to one of the fluid ports communicating through the wall of the containment vessel and delivered to the well and can be withdrawn from the well and returned to the reservoir. A removable cover can be sealed over the upper opening of the containment vessel. The cover can be removed for visual inspection and manual manipulation of the lavage fluid and the patient's viscera. An air evacuation system can be connected to the fluid port and can evacuate aerosols and gasses from within the containment vessel. A heater can be used to heat the perfusion fluid when carrying out hyperthermic perfusion. The apparatus can be left in place on a patient for up to 5-10 days particularly when using cell-cycle specific chemotherapy agents which require long-term contact with tissues in order to achieve their optimal effect. Similarly, the apparatus can be used for repeated access to the abdomino-pelvic space in patients with peritonitis or pancreatitis. Excerpt(s): This invention relates to surgical appliances and methods, and more particularly to an improved apparatus and method for perfusion and lavage of an abdomino-pelvic area both during and after surgery; and in particular when using cellcycle specific chemotherapy drugs which require long-term contact with tissues in order to achieve their optimal effect. By allowing prolonged and repeated access to an abdominal cavity the apparatus can assist in the management of serious intra-abdominal infections. Additionally, by permitting repeated access to the abdominal cavity, the apparatus is adapted for non-oncologic use in the treatment of intra-abdominal sepsis, peritonitis and pancreatitis. One of the mechanisms of the dissemination of gastrointestinal and gynecologic cancers is the intraperitoneal dissemination of the disease. Without special treatments all patients with peritoneal dissemination of cancer die; most patients die within one year. In an attempt to improve the control of intraabdominal cancer, large doses of anti-cancer drugs can be injected directly into the peritoneal cavity. This therapy has shown beneficial effects in selected patients. Also other therapies in addition to intraperitoneal chemotherapy have been developed in an effort to better control the peritoneal dissemination of cancer. It has been observed that hyperthermia seems to have a direct anti-cancer effect and synergy with some types of anti-cancer drugs, so that the toxicity for cancer cells is significantly increased at an elevated temperature. Examples of chemotherapy drugs which have been found effective in hyperthermic perfusion of the peritoneal cavity are cisplatin (CDDP) and mitomycin C (MMC). Accordingly, hyperthermic peritoneal lavage with a chemotherapy solution has been utilized to wash away free cancer cells in the peritoneal cavity by irrigation with a large volume of perfusate, to kill cancer cells by hyperthermia, and to kill cancer cells by the direct effects of chemotherapy. However, due to the inherent long and short term toxicity of chemotherapy solutions to operating room personnel, lavage with a chemotherapy solution can only be safely performed in a

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contained environment that prevents splashing, spillage and aerosol contaminants from escaping into the local atmosphere creating an environmental hazard to health care personnel. Web site: http://www.delphion.com/details?pn=US06383162__ •

Assay of free and complexed trypsinogen-2 Inventor(s): Hedstrom; Johan (Helsingfors, FI), Stenman; Ulf-H.ang.kan (Heikelsvagen 10, Grankulla, FI) Assignee(s): Stenman; Ulf-Hakan (Grankulla, FI) Patent Number: 5,976,809 Date filed: August 13, 1997 Abstract: The invention relates to an immunoassay for trypsinogen-2 wherein an amount of analyte in a sample is measured, said analyte being either trypsin-2 complexed with alpha-1-antitrypsin (trypsin-2-AAT) in serum, or trypsinogen-2 in urine. According to a preferred embodiment, the trypsin-2-AAT complex or free trypsinogen-2 are measured by non-competitive methods employing at least two different antibodies. The methods are useful for the diagnosis of patients with pancreatic disease, especially pancreatitis. Excerpt(s): The present invention provides an immunoassay for the measurement of trypsinogen-2 either as free trypsinogen-2 in urine or as its complex with alpha-1antitrypsin (trypsin-2-AAT) in serum. The invention relates further to a method for differentiating between pancreatitis and other pancreatic disease on one hand and nonpancreatic gastrointestinal disease on the other hand by determining either free trypsinogen-2 in urine or trypsin -2-AAT in serum. The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference. The trypsinogens are serine proteases secreted by exocrine cells of the pancreas (Travis J and Roberts R. Biochemistry 1969; 8: 2884-9; Mallory P and Travis J, Biochemistry 1973; 12: 2847-51). Two major types of trypsinogen isoenzymes have been characterized, trypsinogen-1, also called cationic trypsinogen, and trypsinogen-2 or anionic trypsinogen. The trypsinogen proenzymes are activated to trypsins in the intestine by enterokinase, which removes an activation peptide from the N-terminus of the trypsinogens. The trypsinogens show a high degree of sequence homology, but they can be separated on the basis of charge differences by using electrophoresis or ion exchange chromatography. The major form of trypsinogen in the pancreas and pancreatic juice is trypsinogen-1 (Guy CO et al., Biochem Biophys Res Commun 1984; 125: 516-23). In serum of healthy subjects, trypsinogen-1 is also the major form, whereas in patients with pancreatitis, trypsinogen-2 is more strongly elevated (Itkonen et al., J Lab Clin Med 1990; 115:712-8). Trypsinogens also occur in certain ovarian tumors, in which trypsinogen-2 is the major form (Koivunen et al., Cancer Res 1990; 50: 2375-8). Trypsin-1 in complex with alpha-1-antitrypsin, also called alpha-1-antiprotease, has been found to occur in serum of patients with pancreatitis (Borgstrom A and Ohlsson K, Scand J Clin Lab Invest 1984; 44: 381-6) but determination of this complex has not been found useful for differentiation between pancreatic and other gastrointestinal diseases (Borgstrom et al., Scand J Clin Lab Invest 1989; 49:757-62). Web site: http://www.delphion.com/details?pn=US05976809__

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Composition to improve digestibility and utilization of nutrients Inventor(s): Scharpe; Simon Lodewijk (Wieze, BE) Assignee(s): Medzyme N.V. and Simon Lodewijk Scharpe (BE) Patent Number: 6,051,220 Date filed: February 25, 1998 Abstract: The invention relates to a composition to improve digestibility and utilisation of nutrients, comprising one or more acid stable lipases and/or one or more acid stable amylases. Both the lipase and the amylase may be of fungal origin. The lipase preferably originates from Rhizopus arrhizus or Rhizopus javanicus and the amylase from Aspergillus niger. The composition is for example a pharmaceutical composition for use in the treatment of exocrine pancreas insufficiency which may be the result of or a sideeffect of acquired chronic pancreatitis, alcoholism, cystic fibrosis or pancreatic carcinomas. Excerpt(s): The present invention relates to a composition for the improvement of digestibility and utilisation of nutrients. The invention also relates to the use of fungal acid stable amylase and acid stable lipase for the treatment of clinical conditions associated with an inadequate digestive capacity such as exocrine pancreas insufficiency and in the preparation of these compositions. The efficiency with which nutrients are absorbed (and thus utilized) by the human and animal body depends among other things on the efficiency of digestion. Digestion is inter alia mediated by various enzymes that have specific functions at various locations in the digestive tract. Impairment of the activity of these enzymes will have an influence on the degradation of the food constituents and consequently on the up-take of nutrients. An impaired up-take will inter alia result in reduced growth. In the whole process of digestion the pancreas has an important role. It secretes a juice having two major components, an alkaline fluid and enzymes, into the duodenum. The two components occur in variable proportions depending on the stimuli. The alkaline fluid component, ranging in volume from 200800 ml/day, has a high concentration of bicarbonate, which neutralizes the gastric content entering the duodenum and helps to regulate the pH of the intestinal tract. Web site: http://www.delphion.com/details?pn=US06051220__

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Compounds Inventor(s): Burgess; Nicola Anne (Edmonton, GB), Clinkenbeard; Helen Elizabeth (Hertford, GB), Southan; Christopher Donald (Bishop's Stortford, GB) Assignee(s): SmithKline Beecham p.l.c. (Middlesex, GB) Patent Number: 6,100,059 Date filed: April 30, 1998 Abstract: HGBAB90 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing HGBAB90 polypeptides and polynucleotides in the design of protocols for the treatment of pulmonary emphysema, arthritis, multiple sclerosis, periodontal disease, cystic fibrosis, respiratory disease, thrombosis, cancer, cachexia, angina, glaucoma, inflamatory disorders, osteoporosis, cardiovascular disorders such as hypertension, atherosclerotic disorders such as cardiac infarction, and stroke, asthma, psoriasis, chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's,

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demyelinating diseases, AIDS immune deficiency, disorders of photoreceptor degeneration, and lens cataract formation, organ transplant rejection, cataracts, restenosis, muscular dystrophy, renal failure, cerebral vasospasm, pancreatitis, and diabetic nephropathy, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to serine protease family, hereinafter referred to as HGBAB90. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. Proteases perform a variety of important functions in human physiology. Increasingly diseases are being identified where proteases are critical for the pathology of a particular disease. For these key proteases designing or screening for selective antagonists or agonists can lead to the development of new drugs. The serine proteases are a major family of proteases for which a large number are known. These have been reviewed by Rawlings & Barrett, (Methods Enzymol 244: 19-61, 1994). An example of the serine proteases is the mouse neuropsin (Chen et al. J Neurosci 15 (7 Pt 2): 5088-5097 1995). There remains a need for identification and characterization of further members of the serine protease family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, pulmonary emphysema, arthritis, multiple sclerosis, periodontal disease, cystic fibrosis, respiratory disease, thrombosis, cancer, cachexia, angina, glaucoma, inflamatory disorders, osteoporosis, cardiovascular disorders such as hypertension, atherosclerotic disorders such as cardiac infarction, and stroke, asthma, psoriasis, chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's, demyelinating diseases, AIDS immune deficiency, disorders of photoreceptor degeneration, and lens cataract formation, organ transplant rejection, cataracts, restenosis, muscular dystrophy, renal failure, cerebral vasospasm, pancreatitis, and diabetic nephropathy. Web site: http://www.delphion.com/details?pn=US06100059__ •

Detection of pancreatitis-associated protein for screening for cystic fibrosis Inventor(s): Dagorn; Jean-Charles (Marseilles, FR), Iovanna; Juan-Lucio (Marseilles, FR), Keim; Volker (Heddesheim, DE), Sarles; Jacques (Gemenos, FR) Assignee(s): Institut National de la Sante et de la Recherche Medicale (Paris, FR) Patent Number: 5,834,214 Date filed: August 30, 1995 Abstract: The invention relates to in vitro detection of human pancreatitis-associated protein (hPAP) for the purpose of screening for cystic fibrosis. hPAP is quantitated in a biological sample, preferably blood, and a high value is indicative of pancreatic dysfunction. Immunoassays as rapid, reliable methods for hPAP quantitation are provided as are antibodies for use in the assays and hybridomas for production of monoclonal antibodies preferred for use in the assays. Excerpt(s): The human pancreatitis-associated protein (PAP) was isolated, purified and characterized in man and described in the PCT patent application published on 31 Oct. 1991 under the No 91/16428. In the earlier application the PAP was suggested as a means for the detection of a specific disease, acute pancreatitis. Mucoviscidosis, also called "cystic fibrosis" in English is a very frequent genetic disease in certain populations, which is characterized by a global insufficiency of exocrine secretions of

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the pancreas and the lung and the exocrine glands in general. Clinically, the disease is associated with abnormally viscous secretions, the mucus formed being capable of obstructing the bronchi and causing serious or mortal disorders. The mucoviscidosis gene has been localized on human chromosome 7. This gene, called the CFTR gene ("cystic fibrosis transmembrane conductance regulator") shows mutations in different regions in the subjects suffering from mucoviscidosis. Mutations of the same type may be detected on only one of the two chromosomes 7 in subjects called "carriers" but not showing clinical signs of the disease. These persons are heterozygous for the mutation in the CFTR gene. Web site: http://www.delphion.com/details?pn=US05834214__ •

Healing device applied to persistent wounds, fistulas, pancreatitis, varicose ulcers, and other medical or veterinary pathologies of a patient Inventor(s): Fernandez; Ernesto Ramos (Artigas 1087 1 flr, A, Buenos Aires, AR) Assignee(s): none reported Patent Number: 6,203,563 Date filed: May 26, 1999 Abstract: A healing device applied to wounds, fistulas, pancreatitis, varicose ulcers, and other medical or veterinary pathologies includes a compacting chamber for covering the wound over the affected or diseased zone of the patient. The compacting chamber is defined by a self adhesive polymeric material laminar sheet, made out of a waterproof material. The compacting chamber has a replaceable mass of aerated polymer fiber flock therewithin, as a wound-stabilizing dressing. The compacting chamber uses a vacuum for deforming and compacting a mass of polymer fiber flock into effective healing contact with the wound. The vacuum means is terminated upon achieving compaction of the mass of polymer fiber flock and upon effective healing contact of the mass of polymer fiber flock with the wound. Excerpt(s): The main object for this invention is a healing device applied to wounds, fistulas, pancreatis, varicose ulcers and other medical or veterinary pathologies requiring compacting into said wound an aerated material by means of atmospheric depression, and it has as its secondary object the method for applying said device. It is well know to professionals skilled in the art of healing, that a wound at any part of the human body can be provoked either by a pathological agent, as well through a traumatic agent. In either cases, the final result is a wound which segregates fluids, accumulates detritus and creates a bacteria breeding site, which in direct function of the nature and size of the wound, may impede its healing. On the other hand, a fistula is an orifice open from within an organ or limb in the human body, with an outlet. A healing process implies cleansing the wound, drying same of noxious fluids, and since a wound may be considered as an infectious cavity within the body, a fistula is a wound defining a passage or opening communicating one of more internal organs with the outer environment. The healing process for these medical pathologies are successful when the wound is clean and dry, ceasing in its emission of humorous fluids and detritus. Most of these are provoked by the activity of bacteria and pathogenic agents, which according to their nature must have a sufficient threshold of oxygen pressure in order to live and multiply, or in the case of gangrene, the absence of oxygen is required for same to infest the body. Web site: http://www.delphion.com/details?pn=US06203563__

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Human elastate IV Inventor(s): Adams; Mark D. (North Potomac, MD), Green; John M. (Gaithersburg, MD) Assignee(s): Human Genome Sciences, Inc. (Rockville, MD) Patent Number: 5,851,814 Date filed: April 24, 1997 Abstract: Human elastase IV polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptide by recombinant techniques and utilizing such polypeptide for therapeutic purposes, for example, restoration of elasticity of arterial walls, improvement of serum lipid abnormality and improvement of serum lipoprotein metabolism are disclosed. Also disclosed are antagonist/inhibitors against such polypeptides and their use in treating inflammation, arthritis, e.g. rheumatoid arthritis and osteoarthritis, septic shock, pancreatitis and limiting tissue damage in ulceration. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptide of the present invention is Human Elastase IV, sometimes hereinafter referred to as "HE IV". The invention also relates to inhibiting the action of such polypeptides. Elastase is a serine protease, capable of hydrolyzing the fibrous insoluble protein known as elastin. Elastin is a scleroprotein forming connective tissues, tendons, aortic integuments and cervical bundles of higher animals. Elastin is only slightly degraded by other proteases such as pepsin and trypsin. During the course of study on arteriosclerosis, Balo, et al. observed degradation of the elastin fibers of arterial walls, and postulated the presence of a degrading enzyme (Schweiz, Z., Pathol. Bacteriol., 12: 350 (1949)). Subsequently, in 1952, Banga discovered an enzyme in the pancreas which specifically hydrolyses elastin. The enzyme was isolated in the form of crystals and named elastase (Acta. Physiol. Acad. Sci. Hung, 3: 317 (1952). Web site: http://www.delphion.com/details?pn=US05851814__

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Human pancreatitis-associated protein Inventor(s): Goli; Surya K. (Sunnyvale, CA), Hillman; Jennifer L. (Mountain View, CA) Assignee(s): Incyte Pharmaceuticals, Inc. (Palo Alto, CA) Patent Number: 5,935,813 Date filed: March 20, 1997 Abstract: The present invention provides a novel human C-type lectin (human PAP-2) and polynucleotides which identify and encode human PAP-2. The invention also provides expression vectors, host cells, agonists, antibodies or antagonists. The invention also provides methods for treating or preventing diseases associated with expression of human PAP-2. Excerpt(s): The present invention relates to nucleic acid and amino acid sequences of a novel human pancreatitis-associated (PAP) protein, which comprises a soluble C-type

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lectin. This novel human PAP protein shares features with other proteins in the reg/PSP multigene family which are involved in the regulation of cell growth. The present invention relates to the use of these novel sequences in the diagnosis, prevention and treatment of disease. Lectins are proteins which are defined by their ability to bind carbohydrates specifically and to agglutinate cells. Lectins have been shown to be involved in a wide variety of cellular functions including cell-cell and cell-matrix interactions. Lectins are widespread among plants, invertebrates and mammals. Animal lectins have been grouped into four distinct families: 1) C-type lectins, which include selectins; 2) P-type lectins; 3) galectins (formerly termed S-type lectins or S-Lac lectins); and 4) pentraxins ›Barondes SH et al. (1994) J. Biol. Chem. 269:20807-10!. The C-type lectins bind carbohydrate ligands in a Ca.sup.2+ -dependent manner and are structurally related to the asialoglycoprotein receptor. Selectins, a subcategory of the Ctype lectins, are composite transmembrane molecules which are involved in cell-cell interactions. The selectins include lymphocyte homing receptors and platelet/endothelial cell surface receptors ›Stoolman (1989) Cell 56:907-10!. Web site: http://www.delphion.com/details?pn=US05935813__ •

Method for decreasing severity of acute and chronic pancreatitis Inventor(s): Norman, Jr.; James G. (Tampa, FL) Assignee(s): University of South Florida (Tampa, FL) Patent Number: 5,919,444 Date filed: February 20, 1996 Abstract: A method for treating acute or chronic pancreatitis comprising administering an effective amount of an Interleukin-1 (IL-1) block to antagonize IL-1 production, and in one embodiment by inhibiting IL-1 production at the source, or a pharmaceutically acceptable salt thereof to a person who has pancreatitis. One such IL-1 block is an Interleukin-1 converting enzyme (ICE) antagonist. Excerpt(s): The present invention relates to a method for treating acute and chronic pancreatitis. Acute pancreatitis is a common clinical problem which remains evasive of specific therapy (Leach et al., 1992). Each year more than 210,000 admissions to U.S. hospitals are caused by acute pancreatitis while another 150,000 are due to chronic pancreatitis. Pancreatitis is most often caused by alcoholism or biliary tract disease. Less commonly, it is associated with hyperlipemia, hyperparathyroidism, abdominal trauma, vasculitis or uremia. The average length of hospitalization for the acute disease is 12.4 days, with a significant number of patients staying much longer because of associated complications. Chronic ethanol abuse is the most common cause of acute and chronic pancreatitis in the West, yet the pathophysiology of this disease remains poorly understood (Steinberg and Tenner, 1994). There are few medical therapies or pharmacologic agents currently available which have been shown to decrease the severity, duration, complication rate, or mortality for this common disease. Care for these patients, regardless of the etiology, remains primarily supportive, with attention directed towards maintaining an adequate circulating blood volume, supporting renal and respiratory systems, and providing adequate nutrition. This lack of specific therapy has prompted a great number of prospective trials during the past two decades in hopes of finding some way to decrease the progression and severity of this disease. To date, specific therapy remains unknown and a search for new, more effective modalities is necessary.

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Web site: http://www.delphion.com/details?pn=US05919444__ •

Method for determining whether a human patient is susceptible to hereditary pancreatitis, and primers therefore Inventor(s): Ehrlich; Garth D. (Pittsburgh, PA), Gorry; Michael C. (Pittsburgh, PA), Whitcomb; David (9609 Parkedge Dr., Allison Park, PA 15101) Assignee(s): Whitcomb; David (Allison Park, PA) Patent Number: 6,406,846 Date filed: October 14, 1997 Abstract: A method for determining whether a human patient is susceptible to hereditary pancreatitis. The method comprises the steps of obtaining nucleic acid from the human patient. Then there is the step of checking the nucleic acid for a mutation that indicates hereditary pancreatitis. A primer which reacts with a human trypsinogen gene to identify hereditary pancreatitis. A method for detecting in a human a mutation in a trypsinogen gene indicative of hereditary pancreatitis. The invention comprises the steps of obtaining a sample having DNA of the patient. Then there is the step of processing the sample so the DNA will be recognized by a desired restriction enzyme. Next there is the step of introducing the desired restriction enzyme to the DNA wherein the recognizing of the desired restriction enzyme to the DNA indicates the presence of the mutation. Excerpt(s): The present invention is related to determining whether a human patient is susceptible to hereditary pancreatitis. More specifically, the present invention is related to determining whether a human patient is susceptible to hereditary pancreatitis by identifying a single G to A transition mutation in the third exon of cationic trypsinogen, or digesting the trypsinogen gene in exon III with Afl III. Hereditary pancreatitis (HP) is an autosomal dominant disorder with 80% penetrance and variable expressivity [Perrault, J. Hereditary pancreatitis. Gastroenterol. Clin. North Am. 23:743-752 (1994); Madraso-de la Garza, J., Hill, I., Lebenthal, E. Hereditary pancreatitis. In: Go V, ed. The Pancreas: Biology, Pathobiology, and Disease. 2nd ed. New York: Raven, 1095-1101 (1993); Whitcomb, D. C., Preston, R. A., Aston, C. E., Sossenheimer, M. J., Barua, P. S., Zhang, Y., Wong-Chong, A., White, G., Wood, P., Gates, L. K., Jr., Ulrich, C., Martin, S. P., Post, J. C., and Ehrlich, G. D. A gene for hereditary pancreatitis maps to chromosome 7q35. Gastroenterology 110, 1975-1980 (1996); Bodic, L. L., Bignon, J. D., Raguenes, O., Mercier, B., Georgelin, T., Schnee, M., Soulard, F., Gagne, K., Bonneville, F., Muller, J. Y., Bachner, L., and Ferec, C. The hereditary pancreatitis gene maps to long arm of chromosome 7. Hum. Molec. Genet. 5, 549-554 (1996)]. Nearly 100 kindreds have been reported world-wide since the genetic nature of this disorder was recognized by Comfort and Steinberg in 1952 [Madraso-de la Garza, J., Hill, I., Lebenthal, E. Hereditary pancreatitis. In: Go V, ed. The Pancreas: Biology, Pathobiology, and Disease. 2nd ed. New York: Raven, 1095-1101 (1993); Comfort, M. and Steinberg, A. Pedigree of a family with hereditary chronic relapsing pancreatitis. Gastroenterology 21, 54 (1952)]. The majority of the families are of white European ancestry, but affected kindreds have been reported in Japan, India, and among other ethnic groups [Perrault, J. Hereditary pancreatitis. Gastroenterol. Clin. North Am. 23:743-752 (1994)]. HP is characterized by recurrent bouts of severe epigastric pain with onset, usually developing before ten years of age. The clinical, laboratory and pathologic features of HP are indistinguishable from attacks of pancreatitis from other causes. In addition to recurrent acute attacks, many HP patients progress to complicated chronic pancreatitis characterized by pancreatic

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calcifications, pseudocysts, chronic abdominal pain, pancreatic exocrine failure, diabetes mellitus and/or pancreatic cancer [Perrault, J. Hereditary pancreatitis. Gastroenterol. Clin. North Am. 23:743-752 (1994); Madraso-de la Garza, J., Hill, I., Lebenthal, E. Hereditary pancreatitis. In: Go V, ed. The Pancreas: Biology, Pathobiology, and Disease. 2nd ed. New York: Raven, 1095-1101 (1993)]. Despite years of research, no unique morphologic or biochemical markers have been identified for HP, and the pathophysiologic mechanisms that lead to intermittent attacks of acute pancreatitis remain obscure. Therefore, no rational or effective preventative strategies have been developed, and treatment consists solely of supportive care. Because of the absence of biochemical markers specific for HP, attention has focused on identifying the HP disease gene. The availability of a high-density map of the human genome, based on polymorphic simple tandem repeat (STR) markers, and familial S0 linkage analysis made it possible to identify an HP gene locus within the q35 region of chromosome seven [Whitcomb, D. C., Preston, R. A., Aston, C. E., Sossenheimer, M. J., Barua, P. S., Zhang, Y., Wong-Chong, A., White, G., Wood, P., Gates, L. K., Jr., Ulrich, C., Martin, S. P., Post, J. C., and Ehrlich, G. D. A gene for hereditary pancreatitis maps to chromosome 7q35. Gastroenterology 110, 1975-1980 (1996); Bodic, L. L., Bignon, J. D., Raguenes, O., Mercier, B., Georgelin, T., Schnee, M., Soulard, F., Gagne, K., Bonneville, F., Muller, J. Y., Bachner, L., and Ferec, C. The hereditary pancreatitis gene maps to long arm of chromosome 7. Hum. Molec. Genet. 5, 549-554 (1996)]. It was thus desired to identify and sequence the HP gene to determine the site of the disease-causing mutation(s) in an effort to understand the molecular mechanism leading to HP. Several previously mapped genes on chromosome 7q were considered candidates for the HP disease gene because they are known to be expressed in the exocrine pancreas and encode enzymes that could potentially activate digestive enzymes within the pancreas. The hypothesis that pancreatitis results from inappropriate activation of pancreatic proenzymes was first promulgated 100 years ago and subsequently was demonstrated to be an experimental model for pancreatitis [Chiara, H. Ueber selbstverdauung des menschlichen pankreas. Zeitschrift fur heilkunde 17, 69-96 (1896); Steer, M. L., and Meldolesi, J. The cell biology of experimental pancreatitis. N. Engl. J. Med. 316 (3), 14450, (1987)]. Although carboxypeptidase A1 (CPA1) was considered the primary candidate by Le Bodic [Bodic, L. L., Bignon, J. D., Raguenes, O., Mercier, B., Georgelin, T., Schnee, M., Soulard, F., Gagne, K., Bonneville, F., Muller, J. Y., Bachner, L., and Ferec, C. The hereditary pancreatitis gene maps to long arm of chromosome 7. Hum. Molec. Genet. 5, 549-554 (1996)], this gene mapped centromeric to the HP locus defined by obligate recombinations in an HP linkage study [Whitcomb, D. C., Preston, R. A., Aston, C. E., Sossenheimer, M. J., Barua, P. S., Zhang, Y., Wong-Chong, A., White, G., Wood, P., Gates, L. K., Jr., Ulrich, C., Martin, S. P., Post, J. C., and Ehrlich, G. D. A gene for hereditary pancreatitis maps to chromosome 7q35. Gastroenterology 110, 1975-1980 (1996); Stewart, E. A., Craik, C. S., Hake, L., and Bowcock, A. M. Human carboxypeptidase A identifies a Bg1II RFLP and maps to 7q31-qter. Am. J. Hum. Genet. 46 (4): 795-800, (1990); Rommens, J. M., Zengerling, S., Burns, J., Melmer, G., Kerem, B. S., Plavsic, N., Zsiga, M., Kennedy, D., Markiewicz, D., Rozmahel, R., et al. Identification and regional localization of DNA markers on chromosome 7 for the cloning of the cystic fibrosis gene. Am. J. Hum. Genet. 43 (5), 645-63 (1988); Rommens, J. M., Iannuzzi, M. C., Kerem, B., Drumm, M. L., Melmer, G., Dean, M., Rozmahel, R., Cole, J. L., Kennedy D., Hidaka, N., et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 245 (4922): 1059-65 (1989); Martise, T. C., Perlin, M., and Chakravarti, A. Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nature Genetics. 6 (4), 384-90 (1994)] and was, therefore, excluded from further consideration. However, at least eight trypsinogen genes are located on chromosome 7q35 between the STR markers D7S495 and D7S498 and within

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the V and D-C segments of the complex T-cell receptor.beta. chain gene locus (TCR.beta.) [Rowen, L., Koop, B. F., Hood, L. The Complete 685-Kilobase DNA Sequence of the Human_T Cell Receptor Locus. Science (1996)]. Trypsinogen is an inactive proenzyme for trypsin, which becomes active when an eight amino acid aminoterminal peptide is removed. Although small amounts of trypsin are normally generated within the pancreas, this active trypsin is usually rapidly inactivated before pancreatic autodigestion occurs. Thus, the trypsinogen genes were considered primary candidates for the HP disease gene. Web site: http://www.delphion.com/details?pn=US06406846__ •

Method of using IL-11 for inflammation associated with acute pancreatitis Inventor(s): Keith; James (Andover, MA), Schendel; Paul (Wayland, MA) Assignee(s): Genetics Institute, Inc. (Cambridge, MA) Patent Number: 6,274,135 Date filed: June 22, 1999 Abstract: Provided by the present invention are methods of treating a variety of disorders including AIDS, arthritis (rheumatoid arthritis, osteoarthritis, spondyloarthropathies), antibiotic induced diarrheal diseases (Closbidium difficile), multiple sclerosis, osteoporosis, gingivitis, peptic ulcer disease, esophagitis, diabetes, retinitis, uveitis, reperfusion injury after myocardial infarction (MI) or cerebral vascular accident (CVA), aphthous ulcers (oral), atherosclerosis (plaque rupture), prevention of tumor metastases, asthma, preeclampsia, acute pancreatitis, psoriasis, infertility and allergic disorders such as rhinitis, conjunctivitis, and urticaria. Excerpt(s): The present invention relates generally to methods of treating disorders such as AIDS, arthritis (rheumatoid arthritis, osteoarthritis, spondyloarthropathies), antibiotic induced diarrheal diseases (Clostridium difficile), multiple sclerosis, osteoporosis, gingivitis, peptic ulcer disease, esophagitis, diabetes, retinitis, uveitis, reperfusion injury after myocardial infarction (MI), cerebral vascular accident (CVA), aphthous ulcers (oral), atherosclerosis (plaque rupture), prevention of tumor metastases, asthma, preeclampsia, acute pancreatitis, psoriasis, infertility and allergic disorders such as rhinitis, conjunctivitis, and urticaria. Inflammatory responses include a broad range of host reaction to a variety of insults, such as injury, infection, or rejection. It is the over production of mediators that is believed to be associated with a broad range of disorders, including AIDS, arthritis (rheumatoid arthritis, osteoarthritis, spondyloarthropathies), antibiotic induced diarrheal diseases (Clostridium difficile), multiple sclerosis, osteoporosis, gingivitis, peptic ulcer disease, esophagitis, diabetes, retinitis, uveitis, reperfusion injury after myocardial infarction (MI), cerebral vascular accident (CVA), aphthous ulcers (oral), atherosclerosis (plaque rupture), tumor metastases, asthma, preeclampsia, acute pancreatitis, psoriasis, infertility and allergic disorders such as rhinitis, conjunctivitis, and urticaria. These disorders and their symptoms are briefly summarized below. According to the methods of the present invention, IL-11 is administered to modulate the hosts' over reaction to insult thereby treating the following disorders. Web site: http://www.delphion.com/details?pn=US06274135__

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Methods for synthesizing ether compounds and intermediates therefor Inventor(s): Dasseux; Jean-Louis Henri (Brighton, MI), Oniciu; Carmen Daniela (Gainesville, FL) Assignee(s): Esperion Therapeutics, Inc. (Ann Arbor, MI) Patent Number: 6,410,802 Date filed: March 31, 2000 Abstract: The present invention relates to novel ether compounds, compositions comprising ether compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising an ether compound. The compounds, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's Disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents. Excerpt(s): The present invention relates to ether compounds and pharmaceutically acceptable salts thereof; methods for synthesizing the ether compounds; compositions comprising an ether compound or a pharmaceutically acceptable salt thereof; and methods for treating or preventing a disease or disorder selected from the group consisting of a cardiovascular disease, dyslipidemia, dyslipoproteinemia, a disorder of glucose metabolism, Alzheimer's Disease, Syndrome X; a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence, comprising administering a therapeutically effective amount of a composition comprising an ether compound or a pharmaceutically acceptable salt thereof. The ether compounds and compositions of the invention may also be used to reduce the fat content of meat in livestock and reduce the cholesterol content of eggs. Obesity, hyperlipidemia, and diabetes have been shown to play a casual role in atherosclerotic cardiovascular diseases, which currently account for a considerable proportion of morbidity in Western society. Further, one human disease, termed "Syndrome X" or "Metabolic Syndrome", is manifested by defective glucose metabolism (insulin resistance), elevated blood pressure (hypertension), and a blood lipid imbalance (dyslipidemia). See e.g. Reaven, 1993, Annu. Rev. Med. 44:121-131. The evidence linking elevated serum cholesterol to coronary heart disease is overwhelming. Circulating cholesterol is carried by plasma lipoproteins, which are particles of complex lipid and protein composition that transport lipids in the blood. Low density lipoprotein (LDL) and high density lipoprotein (HDL) are the major cholestrol-carrier proteins. LDL are believed to be responsible for the delivery of cholesterol from the liver, where it is synthesized or obtained from dietary sources, to extrahepatic tissues in the body. The term "reverse cholesterol transport" describes the transport of cholesterol from extrahepatic tissues to the liver, where it is catabolized and eliminated. It is believed that plasma HDL particles play a major role in the reverse transport process, acting as scavengers of tissue cholesterol. HDL is also responsible for the removal non-cholesterol lipid, oxidized cholesterol and other oxidized products from the bloodstream. Web site: http://www.delphion.com/details?pn=US06410802__

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Methods for treating disorders in which docosahexaenoic acid (DHA) levels are affected Inventor(s): Alvarez; Juan G. (Boston, MA), Freedman; Steven (Brighton, MA) Assignee(s): Beth Israel Deaconess Medical Center, Inc. (Boston, MA) Patent Number: 6,180,671 Date filed: February 11, 1999 Abstract: A method of treating disorders in which DHA levels are affected is described. The method includes administering to a subject suffering from the disorder a therapeutically affective amount of DHA. This method is particularly useful in treating subjects suffering from a disorder characterized by a defect in the CF, gene, e.g. cystic fibrosis, or a chronic inflammatory disorder, e.g., ulcerative colitis, Crohn's disease, chronic pancreatitis, asthma, rheumatoid arthritis or chronic gastritis. A method of ameliorating affects of cystic fibrosis in a newborn and a method of increasing surfactant levels in a fetus are also described. Excerpt(s): Cystic Fibrosis (CF) is the most prevalent autosomal recessive disorder in the Caucasian population (Gorelick (1991) Gastroenterology 103 :681-693). Approximately 1 in 2000 live births are afflicted with CF and 5% of Caucasians in the United States are carriers of the abnormal CF gene. CF individuals rarely survive past their mid-thirties, and most mortalities are a result of recurrent pulmonary infection and, ultimately, pulmonary failure. Two other major clinical manifestations of CF are pancreatic dysfunction and male infertility. By 1989, the CF gene had been cloned and was found to code for a chloride channel. Activation of the channel in the normal pancreas activates the chloride/bicarbonate exchanger, resulting in a net secretion of bicarbonate into the lumenal space and alkalinization of the pancreatic juice. Mutations in the chloride channel like those found in CF result in a reduced chloride conductance and a reduced ability of ductal cells to secrete bicarbonate into the lumenal space. This results in the formation of inspissated plugs within the ducts leading to obstruction of the pancreatic ducts. In recent years, the focus in CF research has shifted towards the coupling of defective chloride channel function and membrane recycling. Recent research has demonstrated that membrane internalization at the apical plasma membrane of the pancreatic acinar cell is dependent on pH of the acinar lumen (Freedman et al., Eur. J Cell Biol. (1998) 75:153-63), Freedman et al., (1994) Am. J. Physiol. 267:G40-G51, and Freedman et al., (1994) Eur. J. Cell Biol. 65:354-365). Since pH of the acinar lumen is reflective of ductal bicarbonate secretion from the proximal duct cells, a phenomenon regulated via the chloride channel, a coupling may exist between duct and acinar cell function, (Freedman et al., (1994) Am. J. Physiol. 267:G40-G51, and Freedman et al., (1994) Eur. J. Cell Biol. 65:354-365). Research has also confirmed the hypothesis that lack of alkalinization of the acinar lumen leads to inhibition of apical membrane internalization and defective apical endocytosis in pancreatic acinar cells from CF mice. This block in the recycling of membranes following exocytosis leads to eventual deficiency in membranes for reformation of secretory granules. Thus, pancreatic insufficiency appears to be a result of defects in membrane recycling with obstruction of the ducts occurring as a secondary event. Web site: http://www.delphion.com/details?pn=US06180671__

Patents 171

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Monoclonal antibodies against type I phospholipase A.sub.2 as a diagnostic and antiinflammatory therapeutic agent Inventor(s): Hubner-Parajsz; Christa (Tutzing, DE), Scheuer; Werner (Penzberg, DE), Tibes; Ulrich (Frankfurt, DE) Assignee(s): Boehringer Mannheim GmbH (Mannheim, DE) Patent Number: 5,767,249 Date filed: August 8, 1995 Abstract: The invention provides for monoclonal antibodies which specifically bind to type I phospholipase A.sub.2 for use as a diagnostic agent and as an anti-inflammatory therapeutic agent, which is particularly suitable for application in acute pancreatitis. The invention further provides for pharmaceutical compositions including the antibodies of the invention. The invention also provides for a method for treating subjects suffering from inflammatory symptoms and for detecting the activity of type I phospholipase A.sub.2 in a sample. Excerpt(s): The invention concerns the use of monoclonal antibodies against type I phospholipase A.sub.2 for the production of an anti-inflammatory therapeutic agent which is particularly suitable for application in acute pancreatitis. There is neither a causal nor symptomatic therapy for acute pancreatitis (The Merck Manual of Diagnosis and Therapy 15 (1987), pages 763-767). The pathogenetic basis of acute pancreatitis is autolysis of the pancreas. Phospholipase A.sub.2 has been attributed a decisive function in this process. It has a lysing action on the cell membrane and liberates arachidonic acid from the membrane phospholipids in this process. The metabolites of arachidonic acid (prostaglandins and leukotrienes) are an important component of the inflammatory reaction. Phospholipase A.sub.2 occurs in two forms. The phospholipase A.sub.2 designated type I is mainly found in pancreatic tissue and plays an important role in acute pancreatitis. In contrast type II phospholipase A.sub.2 occurs in many different tissues. Web site: http://www.delphion.com/details?pn=US05767249__

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Substituted pyrido[3,2-d]pyrimidines capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family Inventor(s): Bridges; Alexander James (Saline, MI), Denny; William Alexander (Auckland, NZ), Fry; David (Ypsilanti, MI), Kraker; Alan (Ann Arbor, MI), Meyer; Robert Frederick (Ann Arbor, MI), Rewcastle; Gordon William (Auckland, NZ), Thompson; Andrew Mark (Auckland, NZ) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,084,095 Date filed: March 6, 1997 Abstract: Novel 4-substituted amino pyrido [3,2-d]pyrimidine inhibitors of epidermal growth factor receptor family of tyrosine kinases are described, as well as pharmaceutical compositions of the same, which are useful in treating proliferative diseases such as cancer, synovial pannus invasion in arthritis, psoriasis, vascular restenosis and angiogenesis and additionally useful in the treatment of pancreatitis and kidney disease as well as a contraceptive agent.

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Excerpt(s): The present invention relates to bicyclic heteroaromatic compounds which inhibit the epidermal growth factor receptor and related receptors and, in particular, their tyrosine kinase enzymic activity. Cancer is generally a disease of the intracellular signalling system, or signal transduction mechanism. Cells receive instructions from many extracellular sources, instructing them to either proliferate or not to proliferate. The purpose of the signal transduction system is to receive these and other signals at the cell surface, get them into the cell, and then pass the signals on to the nucleus, the cytoskeleton, and transport and protein syntheses machinery. The most common cause of cancer is a series of defects, either in these proteins, when they are mutated, or in the regulation of the quantity of the protein in the cell such that it is over or under produced. Most often, there are key lesions in the cell which lead to a constitutive state whereby the cell nucleus receives a signal to proliferate, when this signal is not actually present. This can occur through a variety of mechanisms. Sometimes the cell may start to produce an authentic growth factor for its own receptors when it should not, the socalled autocrine loop mechanism. Mutations to the cell surface receptors, which usually signal into the cell by means of tyrosine kinases, can lead to activation of the kinase in the absence of ligand, and passing of a signal which is not really there. Alternatively, many surface kinases can be overexpressed on the cell surface leading to an inappropriately strong response to a weak signal. There are many levels inside the cell at which mutation or overexpression can lead to the same spurious signal arising in the cell, and there are many other kinds of signalling defect involved in cancer. This invention touches upon cancers which are driven by the three mechanisms just described, and which involve cell surface receptors of the epidermal growth factor receptor tyrosine kinase family (EGFR). This family consists of the EGF receptor (also known as Erb-B1), the Erb-B2 receptor, and its constituitively active oncoprotein mutant Neu, the Erb-B3 receptor and the Erb-B4 receptor. Additionally, other biological processes driven through members of the EGF family of receptors can also be treated by compounds of the invention described below. The EGFR has as its two most important ligands Epidermal Growth Factor (EGF) and Transforming Growth Factor alpha (TGFalpha). The receptors appear to have only minor functions in adult humans, but are apparently implicated in the disease process of a large portion of all cancers, especially colon and breast cancer. The closely related Erb-B2 Erb-B3 and Erb-B4 receptors have a family of Heregulins as their major ligands, and receptor overexpression and mutation have been unequivocally demonstrated as the major risk factor in poor prognosis breast cancer. Additionally, it has been demonstrated that all four of the members of this family of receptors can form heterodimeric signalling complexes with other members of the family, and that this can lead to synergistic transforming capacity if more than one member of the family is overexpressed in a malignancy. Overexpression of more than one family member has been shown to be relatively common in human malignancies. Web site: http://www.delphion.com/details?pn=US06084095__ •

Transgenic non-human mammals that express human BSSL/CEL Inventor(s): Tornell; Jan Birger Fredrik (Vastra Frolunda, SE) Assignee(s): Astra Aktiebolag (Sodertalje, SE) Patent Number: 5,716,817 Date filed: May 17, 1995 Abstract: The present invention relates to a DNA molecule containing intron sequences and encoding a human protein which is, depending on the site of action, called Bile Salt-

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Stimulated Lipase (BSSL) or Carboxyl Ester Lipase (CEL). The DNA molecule is advantageously used in the production of recombinant human BSSL/CEL, preferably by means of production in transgenic non-human mammals. The recombinant human BSSL/CEL can be used as a constituent of infant formulas used for feeding infants as a substitute for human milk, or in the manufacture of medicaments against e.g. fat malabsorption, cystic fibrosis and chronic pancreatitis. Excerpt(s): Dietary lipids are an important source of energy. The energy-rich triacylglycerols constitute more than 95% of these lipids. Some of the lipids, e.g. certain fatty acids and the fat-soluble vitamins, are essential dietary constituents. Before gastrointestinal absorption the triacylglycerols as well as the minor components, i.e. esterified fat-soluble vitamins and cholesterol, and diacylphosphatidylglycerols, require hydrolysis of the ester bonds to give rise to less hydrophobic, absorbable products. These reactions are catalyzed by a specific group of enzymes called lipases. In the human adult the essential lipases involved are considered to be Gastric Lipase, Pancreatic Colipase-Dependent Lipase (hydrolysis of tri- and diacylglycerols), Pancreatic Phospholipase A2 (hydrolysis of diacylphosphatidylglycerols) and Carboxylic Ester Lipase (CEL) (hydrolysis of cholesteryl- and fat soluble vitamin esters). In the breast-fed newborn, Bile Salt-Stimulated Lipase (BSSL) plays an essential part in the hydrolysis of several of the above mentioned lipids. Together with bile salts the products of lipid digestion form mixed micelles from which absorption occurs. Web site: http://www.delphion.com/details?pn=US05716817__ •

Treatment and prophylaxis of pancreatitis Inventor(s): Fujiwara; Toshihiko (Ebina, JP), Fukami; Masaharu (Yokohama, JP), Horikoshi; Hiroyoshi (Funabashi, JP) Assignee(s): Sankyo Company, Limited (Tokyo, JP) Patent Number: 5,753,681 Date filed: March 17, 1997 Abstract: Insulin sensitizers, especially thiazolidinedione compounds, such as troglitazone, are useful for the treatment and prevention of pancreatitis. Excerpt(s): The present invention relates to a new use for a series of known compounds, including thiazolidinedione compounds, oxazolidinedione compounds, isoxazolidinedione compounds and oxadiazolidinedione compounds, in the treatment and prophylaxis of pancreatitis. Pancreatitis is commonly classified roughly as either acute pancreatitis or chronic pancreatitis depending on whether or not the condition persists after removal of the etiological agent. Except where the context otherwise requires, the term "pancreatitis", as used herein, includes both acute pancreatitis and chronic pancreatitis. Probably about 40% of cases of acute pancreatitis may be attributed to alcohol abuse. Other causes include idiopathic, cholelithiasis, overeating and traumatic origins. The top three causes account for 70 to 80% of this disease. Web site: http://www.delphion.com/details?pn=US05753681__

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Treatment of inflammation with 2,4,6-trihydroxy-alpha-rhomethoxyphenylacetophenone, or its pharmaceutically acceptable derivatives Inventor(s): Malaviya; Ravi (St. Paul, MN), Uckun; Fatih M. (White Bear Lake, MN) Assignee(s): Parker Hughes Institute (Roseville, MN) Patent Number: 6,248,790 Date filed: June 29, 2000 Abstract: 2,4,6-trihydroxy-.alpha.-p-methoxyphenylacetophenone (also identified herein as "D-58"), or its pharmaceutically acceptable derivatives such as salt and ester forms, is administered for inhibiting inflammatory reactions. The treatment can be remedial or prophylactic. Examples of the conditions that can be treated include acute inflammatory reactions and allergic inflammatory reactions, and specific examples include allergy, asthma, arthritis, psoriasis, skin sunburn, inflammatory pelvic disease, inflammatory bowel disease, urethritis, uvitis, senusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, gastritis, enteritis, dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitis and cholangitis. The 2,4,6-trihydroxy.alpha.-p-methoxyphenylacetophenone can be administered by various routes as needed. Excerpt(s): The present invention is directed to the treatment of acute and chronic inflammatory responses, for example resulting from the presence of an allergen, injury, infection, etc. Allergic and acute inflammatory responses to injury, infection, or other tissue damage can set into motion a complex series of events. A variety of host cells that guard the host environment interface, including macrophages, mast cells, and epithelial/epidermal cells serve as the initiators of the inflammatory responses. These cells release various mediators during an inflammatory response, which include histamine, prostaglandins (PGs), leukotrienes (LTs) and proinflammatory cytokines (refs 1-4). These mediators have been implicated in the pathogenesis of a number of acute and chronic inflammatory conditions such as allergy, asthma, arthritis, psoriasis, and skin sunburn (refs 3-5). The release of inflammatory agents is mediated by a cascade of intracellular signaling events which include activation of phosphoinositide turnover (ref 6), increase in cAMP levels (ref 7), activation of protein kinase C, and an increase in intracellular calcium levels and tyrosine phosphorylation of several cytosolic proteins (refs 7 and 8). Considerable efforts have been made for identification of chemical compounds that can interrupt these signaling events as potential anti-inflammatory agents (refs 9-12). However, the need for agents providing improved inhibition continues. In accordance with the present invention, 2,4,6-trihydroxy-.alpha.-pmethoxyphenylacetophenone (also identified herein as "D-58"), or its pharmaceutically acceptable derivatives such as salt and ester forms, is administered for inhibiting inflammatory reactions to a subject in need thereof. The treatment can be remedial or prophylactic. Examples of the conditions that can be treated include acute as well as chronic inflammatory reactions and allergic inflammatory reactions, and specific examples include allergy, asthma, arthritis, psoriasis, skin sunburn, inflammatory pelvic disease, inflammatory bowel disease, urethritis, uvitis, sinusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, gastritis, enteritis, dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitis and cholangititis. The 2,4,6-trihydroxy-.alpha.-p-methoxyphenylacetophenone can be administered by one of a variety of routes as needed. Web site: http://www.delphion.com/details?pn=US06248790__

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

7-[(4'-trifluoromethyl-biphenyl-2-carbonyl)amino]-quinoline-3-carboxylic amides, and methods of inhibiting the secretion of apolipoprotein B

acid

Inventor(s): Ruggeri, Roger; (Waterford, CT), Wilson, Douglas; (Groton, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020132806 Date filed: January 22, 2002 Abstract: This invention relates to compounds of Formula I 1that inhibit the secretion of apolipoprotein B, to pharmaceutical compositions comprising the compounds, and to methods of treating and/or preventing atherosclerosis, obesity, diabetes, hyperlipidemia, hyperliproproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X. This invention also relates to methods of reducing the secretion of apolipoprotein B and/or inhibiting microsomal triglyceride transfer protein. Excerpt(s): This is a divisional application of U.S. application number 09/711,281, filed Nov. 9, 2000, now allowed, which claims priority from U.S. provisional application number 60/164,803, filed Nov. 10, 1999 and U.S. provisional application number 06/224,956, filed Aug. 11, 2000. This invention relates to compounds that inhibit the secretion of apolipoprotein B, and to methods of treating and/or preventing atherosclerosis, obesity, diabetes, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia, pancreatitis, myocardial infarction, stroke, restenosis, or Syndrome X. This invention also relates to methods of reducing the secretion of apolipoprotein B and/or inhibiting microsomal triglyceride transfer protein. Microsomal triglyceride transfer protein (MTP) catalyzes the transport of triglycerides, cholesteryl esters and phospholipids, and MTP is involved in the assembly of lipoproteins that contain apolipoprotein B (apo B). Examples of lipoproteins that contain apo B include lipoprotein (a) [Lp(a)], low density lipoprotein (LDL), and very low density lipoprotein (VLDL), which is a precursor to LDL. Compounds that contain apo B are known to contribute to the formation of atherosclerotic lesions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

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

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AGENT FOR PREVENTING AND/OR TREATING MULTIPLE ORGAN FAILURE Inventor(s): ARISAWA, HIROHIKO; (TOCHIGI, JP), HIGASHIO, KANJI; (SAITAMA, JP), MASUNAGA, HIROAKI; (TOCHIGI, JP), OGAWA, HIROMI; (TOCHIGI, JP) Correspondence: Testa Hurwitz & Thbeault; High Street Tower; 125 High Street; Boston; MA; 02110 Patent Application Number: 20010051146 Date filed: August 27, 1999 Abstract: The present invention is to provide an agent for preventing and/or treating multiple organ failure comprising Tumor cytotoxic factor-II (TCF-II) or Hepatocyte growth factor (HGF) as an effective ingredient.The agent of the present invention will be useful for preventing and/or treating the development from burn, disseminated intravascular coagulation (DIC), circulatory failure, hemorrhagic shock, infectious disease, acute pancreatitis, ischemic disorder, hepatorenal syndrome, gastrointestinal hemorrhage, nutritional metabolic failure, terminal cancer, acquired immunodeficiency syndrome (AIDS), deterioration of systemic conditions due to radiation affection and cachexia etc. to multiple organ failure. Excerpt(s): The present invention relates to a novel agent for preventing and/or treating multiple organ failure. Development from burn, disseminated intravascular coagulation (DIC), circulatory failure, hemorrhagic shock, infectious disease, acute pancreatitis, ischemic disorder, hepatorenal syndrome, gastrointestial hemorrhage, nutritional metabolic failure, terminal cancer, acquired immunodeficiency syndrome (AIDS), deterioration of systemic conditions due to radiation affection and cachexia etc. to multiple organ failure can be prevented or treated by the present invention. Onset or exacerbation of multiple organ failure can be classified into the following 3 categories with respect to mechanism: (1) Parallel induction of several organ disorders due to the same factor; (2) Induction of a specific organ dysfunction due to disorder of an organ; and (3) Participation of an iatrogenic factor. Excessive insults due to severe trauma or major surgeries, infectious diseases, shock etc. directly or through various kinds of mediator participate in the onset or deterioration of multiple organ failure by mechanism (1). In the case of multiple organ failure accompanied with organ disorder due to trauma or primary hepatic insufficiency, participation of mechanism (2) through organ correlation mechanism will largely contribute to the onset or deterioration thereof. By mechanism (3), medical care carried out during intensive care or care to correspond with an organ disorder may result in the other organ disorder. In patients, these 3 mechanisms participate to the development or deterioration of disorder in a complexed manner. The prognosis of patients of multiple organ failure is generally very poor and, in fact, the survival rate is low as 20-30% in spite of a wide variety of corresponding treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Aminoalcohol derivatives and their use as beta 3 adrenergic agonists Inventor(s): Fujii, Naoaki; (Takatsuki-shi, JP), Sakurai, Minoru; (Toyonaka-shi, JP), Takasugi, Hisashi; (Sakai-shi, JP), Taniguchi, Kiyoshi; (Kobe-shi, JP), Tomishima, Yasuyo; (Osaka-shi, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030181726 Date filed: March 4, 2003 Abstract: This invention relates to new aminoalcohol derivatives or salts thereof represented by the following formula [I]: 1wherein each symbol is as defined in the specification or salts thereof which have gut selective sympathomimetic, anti-ulcerous, anti-pancreatitis, lipolytic, anti-urinary incontinence and anti-pollakiuria activities, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment diseases indicated in the specification to a human being or an animal. Excerpt(s): This invention relates to new aminoalcohol derivatives and salts thereof which are.beta.sub.3 adrenergic receptor agonists and useful as a medicament. This invention relates to new aminoalcohol derivatives which are.beta.sub.3 adrenergic receptor agonists and salts thereof. More particularly, it relates to new aminoalcohol derivatives and salts thereof which have gut selective sympathomimetic, anti-ulcerous, anti-pancreatitis, lipolytic, anti-urinary incontinence and anti-pollakiuria activities, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of gastro-intestinal disorders caused by smooth muscle contractions in human beings or animal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Antagonists of MCP-1 function and methods of use thereof Inventor(s): Anuskiewicz, Steven E.; (San Bruno, CA), Inagaki, Hideaki; (Anjoh-shi, JP), Ishiwata, Yoshiro; (Aichi-gun, JP), Jomori, Takahito; (Nagoya-shi, JP), Kakigami, Takuji; (Inabe-gun, JP), Laborde, Edgardo; (Foster City, CA), Matsumoto, Yukiharu; (Gifu-shi, JP), Matsushima, Kouji; (Matsudo-shi, JP), Meng, Fanying; (San Francisco, CA), Peterson, Brian T.; (San Francisco, CA), Robinson, Louise; (San Carlos, CA), Villar, Hugo O.; (La Jolla, CA), Yokochi, Shoji; (Inabe-gun, JP) Correspondence: Heller Ehrman White & Mcauliffe Llp; 275 Middlefield Road; Menlo Park; CA; 94025-3506; US Patent Application Number: 20030105085 Date filed: February 27, 2002 Abstract: Compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection; pharmaceutical compositions comprising these

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compounds; and the use of these compounds and compositions in the prevention or treatment of such diseases. Excerpt(s): This application claims the priority under 35 USC 119(e) of U.S. Provisional Application No. 60/272,792, filed Mar. 1, 2001, which is incorporated herein by reference. The present invention relates to compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection; and to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases. The migration of leukocytes from blood vessels into diseased tissues is an important process in the initiation of normal inflammatory responses to certain stimuli or insults to the immune system. However, this process is also involved in the onset and progression of lifethreatening inflammatory and autoimmune diseases; blocking leukocyte recruitment in these disease states, therefore, can be an effective therapeutic strategy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for inhibiting islet dysfunction and autoimmune disorders Inventor(s): Hill, David J.; (London, CA), Remacle, Claude; (Louvain-la-Neuve, BE), Reusens, Brigitte; (Braine-I'Alleud, BE) Correspondence: Kenneth I. Kohn; Kohn & Associates, Pllc; Suite 410; 30500 Northwestern Highway; Farmington Hills; MI; 48334; US Patent Application Number: 20030180345 Date filed: February 10, 2003 Abstract: The invention relates to a composition comprising an amino acid like structure carrying a sulfur moiety and a biologically acceptable carrier for inhibiting islet dysfunction and/or autoimmune disorders. The structure may be taurine, L-cysteine, Lmethionine, or a combination of these. Conditions of islet dysfunction include insulitis, Type 1 diabetes (IDDM), Type 2 diabetes (NIDDM), mature onset diabetes of the young (MODY), and gestational diabetes. Autoimmune disorders include insulitis, Type 1 diabetes, rheumatoid arthritis, thyroiditis and pancreatitis. The composition can act to inhibit islet dysfunction through exerting anti-apoptotic or immunomodulatory activity. Methods are provided for inhibiting islet dysfunction and/or autoimmune disorders by administering an amino acid like structure carrying a sulfur moiety to an individual. Excerpt(s): This application is a continuation-in-part of International Patent Application PCT/CA01/01137, which was filed Aug. 9, 2001, and published Feb. 21, 2002, and claims the benefit of priority from International Patent Application PCT/CA00/00925, filed on Aug. 11, 2000, which was published Feb. 21, 2002, the entirety of which is herein incorporated by reference. The present invention relates to a compositions and methods for inhibiting pancreatic islet dysfunction and for inhibiting autoimmune disorders. The compositions and methods are prophylactic and therapeutically effective against such conditions as insulitis, Type 1 diabetes, and Type 2 diabetes. Diabetes involves dysfunction of the pancreatic islet cells. In the case of Type 1 diabetes, also referred to as insulin dependent diabetes mellitus (IDDM), dysfunction is initiated in the event of an

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immunological challenge. In the case of Type 2 diabetes, also referred to as non-insulin dependent diabetes mellitus (NIDDM), islet dysfunction occurs in upon exposure to a homeostatic challenge. Diabetes can alter total.beta. cell mass, as well as the properties of individual.beta. cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Feline pancreatic lipase composition and method of preparing and using such composition Inventor(s): Steiner, Jorg M.; (College Station, TX), Williams, David A.; (College Station, TX) Correspondence: Bracewell & Patterson, L.L.P.; Attention: J. Wendy Davis, PH.D.; P.O. Box 61389; Houston; TX; 77208-1389; US Patent Application Number: 20030207333 Date filed: May 2, 2003 Abstract: A novel form of lipase, namely feline pancreatic lipase (also termed feline classical pancreatic lipase) has an N-terminal amino acid sequence as shown in SEQ ID NO. 1. A method of purifying this lipase includes collecting pancreatic tissue from cats, delipidating the pancreatic tissue to produce a delipidated pancreatic extract, extracting pancreatic lipase from the delipidated pancreatic extract, and eluting the extracted pancreatic lipase through various columns. This lipase can be used for measuring pancreatic lipase immunoreactivity in serum thereby diagnosing pancreatitis in cats. To do so, antiserum against feline pancreatic lipase is prepared, and immunoassays are then performed in serum samples using this antiserum. In the event that increased concentration of pancreatic lipase immunoreactivity above the control range is detected in the serum, the cat might have pancreatitis. Excerpt(s): This nonprovisional application claims priority of U.S. Provisional Patent Application Serial No. 60/377,522, filed on May 3, 2002. The present invention relates generally to the field of biology and medicine. More particularly, the present invention relates to feline pancreatic lipase compositions, methods for preparing such compositions, and methods for employing such compositions to detect the concentration of pancreatic lipase in cat serum for diagnosis and management of pancreatitis. Lipases are water-soluble enzymes that hydrolyze water-insoluble substrates into more polar lipolysis products (Petersen and Drabl.o slashed.s, 1994). In 1856 Claude Bernard identified the first lipase (Petersen and Drabl.o slashed.s, 1994). Since then a plethora of lipases has been identified in microorganisms, plants, and animals (Lin et al., 1986; Jaeger et al., 1994; Petersen and Drabl.o slashed.s, 1994; Mukherjee and Hills, 1994; Lawson et al., 1994). Lipases share a common triad of amino acids (serine, aspartic or glutamic acid, and histidine) in the active site, which is also shared with serine proteases (Svendsen, 1994). Another common feature of almost all lipases are glycosylation site motifs (Antonian, 1988). Many lipases have been shown to be related phylogenetically. The pancreatic lipase gene family is a large gene family with 9 subfamilies (Petersen and Drabl.o slashed.s, 1994; Carrire et al., 1997; Carrire et al., 1998; Hirata et al., 1999). In addition there are other groups of phylogenetically related lipases, and yet other lipases that do not belong to a defined gene family (Anderson and Sando, 1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Glypican-1 in human breast cancer Inventor(s): Korc, Murray; (Irvine, CA), Lander, Arthur D.; (Laguna Beach, CA) Correspondence: Reed Smith Crosby Heafey Llp; 1901 Avenue OF The Stars, Suite 700; Los Angeles; CA; 90067; US Patent Application Number: 20030103980 Date filed: July 31, 2002 Abstract: Glycosylphosphatidylinositol-(GPI-) anchored HSPG glypican-1 is strongly expressed in human breast and pancreatic cancer--both by the cancer cells and in the case of pancreatic cancer the adjacent fibroblasts--whereas expression of glypican-1 is low in the normal pancreas and in chronic pancreatitis. Treatment of two pancreatic cancer cell lines, which express glypican-1, with the enzyme phosphoinositide-specific phospholipase-C (PI-PLC) abrogated their mitogenic responses to two heparin-binding growth factors: fibroblast growth factor-2 (FGF2) and heparin-binding EGF-like growth factor (HB-EGF). Treatment of MDA-MB-231 and MDA-MB-468 breast cancer cells with PI-PLC abrogates the mitogenic response to two heparin-binding growth factors, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and fibroblast growth factor-2 (FGF-2). Syndecan-1 is also expressed at high levels in breast cancer tissues as well as breast cancer cells by comparison with breast normal tissues. Temporary or permanent transfection of a glypican-1 antisense construct attenuated glypican-1 protein levels and the mitogenic response to FGF2 and HB-EGF. Glypican can be used to detect the carcinoma in vitro and therapeutics that either bind to (e.g., antibodies or drugs), remove (e.g., enzymes) or prevent the expression (e.g., antisense constructs) of surface of the extracellular domain of glypican-1 are effective in retarding the growth of glypican-responsive carcinomas. Excerpt(s): The present application is a continuation-in-part of application Ser. No. 09/807,575, filed on Jul. 12, 2001, which is the National Phase filing of PCT/US99/24176, filed on Oct. 15, 1999, which claims priority from U.S. Provisional Application No. 60/104,510 (filed Oct. 16, 1998) and Ser No. 60/121,624 (filed Feb. 25, 1999). The present application is also a continuation-in-part of and claims priority from U.S. Provisional Application No. 60/309,722 (filed Jul. 31, 2001). All of the above applications are incorporated herein by reference. The present application concerns medical sciences and more particularly detection and treatment of human cancers, especially breast cancer. Membrane associated heparan sulfate proteoglycans (HSPGs) are thought to play important roles in many aspects of cell behavior, including cell-cell and cell-extracellular matrix adhesion (59, 104) and growth factor signaling (13, 89). Two families of polypeptides appear to carry the majority of the heparan sulfate on mammalian cells: glypicans, which are attached to the plasma membrane via glycosylphophatidylinositol (GPI) anchors, and syndecans, which are transmembrane proteins (13, 7). Four syndecans and five glypicans, all encoded by separate genes, have been described to date (6, 14, 107, 23, 117 and 97). Many of these polypeptides exhibit tissue specific patterns of expression, although these patterns often overlap (38, 64, 2 and 9). In vitro, at least, it is common for cells to express multiple HSPGs, often from both the glypican and syndecan families. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Heterocyclic carboxamide derivatives as inhibitors of nitric oxide production Inventor(s): Ohkawa, Takehiko; (Ibaraki, JP), Ohne, Kazuhiko; (Ibaraki, JP), Oku, Teruo; (Tokyo, JP), Setoi, Hiroyuki; (Ibaraki, JP), Shima, Ichiro; (Ibaraki, JP), Yoshihara, Kousei; (Ibaraki, JP), Zenko, Tatsuya; (Tokyo, JP) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20020132809 Date filed: February 25, 2002 Abstract: 1wherein each symbol is as defined in the specification, and pharmaceutically acceptable salts thereof. The compound (I) of the present invention and pharmaceutically acceptable salts thereof possess a strong inhibitory activity on the production of nitric oxide (NO), and are useful for prevention and/or treatment of NOmediated diseases such as adult respiratory distress syndrome, cardiovascular ischemia, myocarditis, heart failure, synovitis, shock, diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, glomerulonephritis, peptic ulcer, inflammatory bowel disease, cerebral infarction, cerebral ischemia, cerebral hemorrhage, migraine, rheumatoid arthritis, gout, neuritis, postherpetic neuralgia, osteoarthritis, osteoporosis, systemic lupus erythematosus, rejection by organ transplantation, asthma, metastasis, Alzheimer's disease, arthritis, CNS disorders, dermatitis, hepatitis, liver cirrhosis, multiple sclerosis, pancreatitis, atherosclerosis, and the like in human being and animals. Excerpt(s): This invention relates to new amide compounds and pharmaceutically acceptable salts thereof which are useful as medicament. Some peptide compounds have been known as described in, for example, EP 0 394 989 A2. This invention relates to new amide compounds. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Immunoprotective methods for beta cell neogenesis Inventor(s): Van Antwerp, William P.; (Valencia, CA) Correspondence: Gates & Cooper Llp; Howard Hughes Center; 6701 Center Drive West, Suite 1050; Los Angeles; CA; 90045; US Patent Application Number: 20030212000 Date filed: May 9, 2003 Abstract: The invention is based on the disclosure provided herein that a biologically active fragment of pancreatitis associated polypeptide can be used to stimulate beta cell growth and at the same avoid and overcome the T-cell mediated autoimmune attack on the pancreas. Typical embodiments of the invention include methods of inhibiting the onset of Type I diabetes in a mammalian subject predisposed to Type I diabetes comprising administering to the subject a therapeutically effective amount of a pancreatitis associated polypeptide comprising the amino acid sequence IGLHDPTQGTEPNGE (SEQ ID NO: 3). Excerpt(s): This application claims the benefit of U.S. provisional patent application serial No. 60/379,202, filed May 9, 2002. The entire content of this provisional patent application is incorporated herein by reference. The present invention relates to the prevention and treatment of diseases associated with pancreatic dysfunction. Of the

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millions of individuals who are afflicted with diabetes, a large portion of them suffer from Type I diabetes, a syndrome caused by a lack of insulin which results from the loss of function and/or the destruction of insulin producing beta cells that are found in the pancreatic islets. In non-diabetic individuals, the beta cells produce sufficient amounts of insulin, a polypeptide which functions to regulate the ability of various tissues to absorb glucose as well as to maintain a steady blood-glucose concentration. If the body is unable to produce sufficient amounts of insulin, a high concentration of glucose will remain in the blood, and organs will not receive the glucose needed to function properly. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Leptin-mediated gene-induction Inventor(s): Broekaert, Daniel; (Waarschool, BE), Tavernier, Jan; (Balegem, BE), Vandekerckhove, Joel S.; (Loppem, BE), Verhee, Annick; (Lichtervelde, BE), Waelput, Wim; (Nieuwerkerken-waas, BE) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030036526 Date filed: September 4, 2002 Abstract: Methods of activating a signaling cascade comprising, introducing leptin and/or a cytokine to a receptor complex comprising gp 130, optionally in combination with a compound acting on adenylate cyclase or acting on one or more downstream targets of adenylate cyclase, thereby inducing genes in neuro-endocrine cells or cells of neuro-endocrine origin. Two distinct gene-sets are induced, immediate early response genes (STAT-3, SOCS-3, Metallothionein-II, the serine/threonine kinase Fnk and the rat homologue of MRF-1), and late induced target genes (Pancreatitis Associated Protein I, Squalene Epoxidase, Uridinediphosphate Glucuronyl Transferase and Annexin VIII). Strong co-stimulation with the adenylate cyclase activator forskolin was shown with respect to late induced target genes. Transcripts encoding Leptin Induced Protein I (LIPI) and Leptin Induced Protein II (LIP-II) were identified; however, no forskolin costimulatory effect was observed. It is also demonstrated that leptin modulates in vivo expression of MT-II, Fnk and Pancreatitis Associated Protein I genes. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 09/770,735, filed on Jan. 26, 2001 now U.S. Pat. No.______, which is a continuation of International Application No. PCT/EP99/05489, filed on Jul. 27, 1999, designating the United States of America, (International Publication No. WO 00/017014, published Feb. 10, 2000) the entire contents of each of which are incorporated by this reference. The current invention relates to leptin and/or a cytokine that binds to a receptor complex comprising gp 130, optionally in combination with a compound acting on adenylate cyclase or one of its downstream targets, to activate a signaling cascade wherein, as a result thereof, immediate early response and/or late target genes are induced in neuroendocrine cells or in cells of neuro-endocrine origin. In healthy conditions, assimilation, storage and utilization of nutrient energy constitute a highly integrated homeostatic system. Maintaining a relatively constant level of energy stores, and hence body weight, requires the achievement of a balance between food intake and energy expenditure. The "set point" hypothesis proposes coordinated regulation by control centers in the central nervous system. Hypothalamic nuclei are believed to be the sites at which the "set point" is regulated, given their important role in establishing homeostasis through regulation of food intake (hunger versus satiety), body weight, energy expenditure (adaptive

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thermogenesis) and hormone integration involving substrate inter-conversion, storage and mobilization as appropriate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Macromolecular enzyme substrates Inventor(s): Hortin, Glen L.; (Gaithersburg, MD) Correspondence: Needle & Rosenberg, P.C.; Suite 1000; 999 Peachtree Street; Atlanta; GA; 30309-3915; US Patent Application Number: 20030186345 Date filed: January 30, 2003 Abstract: The present invention features methods for measuring the activity of an enzyme (such as a proteinase or an endosaccharidase) in a sample, using a macromolecular substrate of the enzyme. Also featured are methods for: detecting the level of peptidase activity of a proteinase; measuring amylase activity in a sample; diagnosing pancreatitis in a subject; measuring the activity of a target isoenzyme in a sample; identifying a compound that modulates the activity of a proteinase or an endosaccharidase; and identifying an antibody that modulates the activity of a proteinase or an endosaccharidase, using the macromolecular substrates provided by the present invention. Excerpt(s): This application claims benefit of priority to U.S. Ser. No. 60/221,790, filed Jul. 31, 2001. This invention relates generally to measurement of enzyme activity using synthetic macromolecular enzyme substrates. Artificial substrates are commonly used in a broad variety of clinical, industrial, and research assays to measure the activities of various enzymes. One significant drawback of artificial substrates, however, is that they usually are substantially smaller than the natural substrate of the enzyme for which activity is being measured. The small size of these artificial substrates often limits the accuracy and/or sensitivity of an assay employing such a substrate, thereby leading to inaccurate estimates of enzyme activity in a sample. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for treating and preventing pancreatitis Inventor(s): Cohard, Marielle; (Summit, NJ), Deviere, Jacques; (Genappe, BE) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20030133906 Date filed: November 26, 2002 Abstract: This invention relates to the use of interleukin-10 (IL-10) for the prevention and treatment of pancreatitis. It provides methods for preventing the onset or worsening of pancreatitis in patients at risk of developing such condition by administering a therapeutically effective amount of IL-10. In a specific embodiment, IL10 is administered to patients at risk of developing pancreatitis due to a procedure such as endoscopic retrograde pancreotography.

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Excerpt(s): This application is a non-provisional application that claims priority under 35 U.S.C.sctn. 119(e) of provisional application, U.S. Ser. No. 60/333,983 filed Nov. 28, 2001, the contents of which are hereby incorporated by reference in their entireties. This invention relates to the use of interleukin-10 (IL-10) for the prevention and treatment of pancreatitis, and the like. Acute pancreatitis is a major complication of endoscopic retrograde cholangiopancreatography (ERCP). Unlike hemorrhage, duodenal perforation, or cholangitis, the incidence of pancreatitis has not decreased with the technical improvements of recent years and expertise of the operators [Freeman et al., N. Engl. J. Med. 335:909-918 (1996); Huibregtse K, N. Engl. J. Med. 335:961-963 (1996)]. The risk of post-ERCP pancreatitis varies greatly with the indications, being <5% for management of common bile duct (CBD) stones and reaching 20% or more in cases of suspected sphincter of Oddi dysfunction (SOD) and manipulation of small bile ducts or of a well-functioning pancreatic gland in young patients [Freeman et al., supra; Sherman et al., Gastroenterology 101:1068-1075 (1991); Sherman et al., Gastrointest. Endosc. 36:462-466 (1990); Messmann et al., Gut 40:80-85 (1997); Loperfido et al., Gastrointest. Endosc. 48:1-10 (1998)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of detecting procarboxypeptidase A and carboxypeptidase A levels in biological fluids Inventor(s): Gilvarg, Charles; (Princeton, NJ) Correspondence: Licata & Tyrrell P.C.; 66 E. Main Street; Marlton; NJ; 08053; US Patent Application Number: 20010055785 Date filed: June 12, 2001 Abstract: Methods of enhancing sensitivity and specificity of an assay measuring enzymatic activity in a sample by measuring enzymatic activity in the sample in the presence and absence of a specific inhibitor of the enzymatic activity are provided. Methods of measuring carboxypeptidase A levels and total carboxypeptidase A levels, wherein procarboxypeptidase A is converted to carboxypeptidase A by addition of clostripain, in a biological fluid with a carboxypeptidase A substrate, specificity of which is enhanced by addition of a carboxypeptidase A specific inhibitor are also provided. In addition, methods of diagnosing acute pancreatitis by measurement of carboxypeptidase A levels and pancreatic cancer by measurement of total carboxypeptidase A levels are also provided. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 09/402,405 filed Oct. 4, 1999, which is the U.S. National Phase of PCT Application PCT/US98/06615 filed Apr. 10, 1998, which claims the benefit of priority from U.S. Provisional Application Serial Nos. 60/055,495 filed Aug. 12, 1997 and 60/041,835 filed Apr. 10, 1997. Determination of altered enzyme levels by measurement of enzyme activity in biological samples is used routinely by clinicians to assist in the diagnosis of a multitude of diseases or conditions wherein physical symptoms alone may not be definitive. However, the usefulness of such assays is dependent upon the specificity of the enzyme to the disease or condition and the sensitivity and selectivity of the enzymatic assay. For example, acute pancreatitis is defined clinically as a discrete episode of symptoms caused by intrapancreatic activation of digestive enzymes. The cause of this activation is unknown; however, premature activation of zymogen to active enzymes within the pancreas results in autodigestion and inflammation of the pancreas. Symptoms include a steady, dull or boring pain in the epigastrium or left upper

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abdominal quadrant which is poorly localized and reaches peak intensity within fifteen minutes to one hour. The incidence of acute pancreatitis is difficult to ascertain as uniform diagnostic criteria and effort have not been applied. However, there is an urgency in accurately diagnosing acute pancreatitis to exclude other acute conditions that require different, usually surgical, management such as perforated peptic ulcer, acute cholangitis, appendicitis and mesenteric infarction. In contrast, pancreatitis is best treated through a "hands off" approach of eliminating food intake and increasing hydration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHODS AND COMPOSITIONS FOR THE TREATMENT OF PANCREATITIS Inventor(s): AOKI, KEI ROGER; (COTO DE CAZA, CA), SACHS, GEORGE; (ENCINO, CA) Correspondence: Allergan Inc; 2525 Dupont Drive; Irvine; CA; 92612 Patent Application Number: 20010018049 Date filed: April 8, 1999 Abstract: Methods and compositions for the treatment of acute pancreatitis in a mammal. Particular compositions comprise a binding element, a translocation element, and a therapeutic element able to prevent accumulation of digestive enzymes within the pancreas. Excerpt(s): The present invention includes methods and compositions for the treatment of acute pancreatitis. In a preferred embodiment the invention concerns the use of agents to reduce or prevent the secretion of pancreatic digestive enzymes within the pancreas. Such agents are targeted to pancreatic cells, and serve to prevent the exocytotic fusion of vesicles containing these enzymes with the plasma membrane. The invention is also concerned with methods of treating a mammal suffering from pancreatitis through the administration of such agents. Pancreatitis is a serious medical condition involving an inflammation of the pancreas. In acute or chronic pancreatitis the inflammation manifests itself in the release and activation of pancreatic enzymes within the organ itself, leading to autodigestion. In many cases of acute pancreatitis, the condition can lead to death. In normal mammals, the pancreas, a large gland similar in structure to the salivary gland, is responsible for the production and secretion of digestive enzymes, which digest ingested food, and bicarbonate for the neutralization of the acidic chyme produced in the stomach. The pancreas contains acinar cells, responsible for enzyme production, and ductal cells, which secrete large amounts of sodium bicarbonate solution. The combined secretion product is termed "pancreatic juice"; this liquid flows through the pancreatic duct past the sphincter of Oddi into the duodenum. The secretion of pancreatic juice is stimulated by the presence of chyme in the upper portions of the small intestine, and the precise composition of pancreatic juice appears to be influenced by the types of compounds (carbohydrate, lipid, protein, and/or nucleic acid) in the chyme. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of treating cytokine mediated diseases Inventor(s): Moss, Neil; (Ridgefield, CT), Regan, John Robinson; (Larchmont, NY) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P O Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20030060455 Date filed: September 9, 2002 Abstract: Disclosed are methods of treating acute and chronic inflammation in the lung caused by inhalation of smoke, endometriosis, Behcet's disease, uveitis, ankylosing spondylitis, pancreatitis, cancer, Lyme disease, sepsis, chronic obstructive pulmonary disease, traumatic arthritis, congestive heart failure and restenosis following percutaneous transluminal coronary angioplasty, known to be cytokine mediated, using aromatic heterocyclic compounds described in WO 00/55139. Excerpt(s): This application claims benefit to U.S. provisional application serial No. 60/318,958 filed Sep. 13, 2001. This invention relates to methods of treating acute and chronic inflammation in the lung caused by inhalation of smoke, endometriosis, Behcet's disease, uveitis, ankylosing spondylitis, pancreatitis, cancer, Lyme disease, percutaneous transluminal coronary angioplasty, Alzheimer's disease, traumatic arthritis, sepsis, chronic obstructive pulmonary disease and congestive heart failure indicated to be cytokine mediated diseases using aromatic heterocyclic compounds disclosed in PCT publication WO 00/55139. In WO 00/55139 there are described aromatic heterocyclic compounds useful in treating certain cytokine mediated diseases. Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are important biological entities collectively referred to as proinflammatory cytokines. These, along with several other related molecules, mediate the inflammatory response associated with the immunological recognition of infectious agents. The inflammatory response plays an important role in limiting and controlling pathogenic infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nitrogen-containing heterocyclic compounds hyperlipidemia comprising the same

and

therapeutic

agents

for

Inventor(s): Hiraiwa, Yukiko; (Yokohama-Shi, JP), Katano, Kiyoaki; (Yokohama-Shi, JP), Kuroda, Chidsuko; (Yokohama-Shi, JP), Matsushima, Tetsuya; (Yokohama-Shi, JP), Nakatani, Yuuko; (Yokohama-Shi, JP), Niizato, Tetsutaro; (Yokohama-Shi, JP), Ohkura, Naoto; (Yokohama-Shi, JP), Shiotani, Masaharu; (Yokohama-Shi, JP), Suzuki, Shigeki; (Yokohama-Shi, JP), Tsuruoka, Takashi; (Yokohama-Shi, JP), Usui, Takayuki; (Yokohama-Shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20020156276 Date filed: April 23, 2002 Abstract: Disclosed are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof. The compounds can inhibit the biosynthesis of triglycerides in the liver and can inhibit the secretion of lipoprotein containing apolipoprotein B from the liver. Therefore, they are useful for the prevention or treatment of hyperlipidemia (particularly hyper-very-low-density-lipoproteinemia) and

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arteriosclerotic diseases, such as cardiac infarction, or pancreatitis induced by hyperlipidemia. 1wherein A represents group --CR.sup.1R.sup.2--( CH.sub.2 ).sub.1-where R.sup.1 and R.sup.2 each represent a hydrogen atom or alkyl, --CH.dbd.CH--, -O--CH.sub.2--, or --S(O).sub.j--CH.sub.2--; B represents a hydrogen or halogen atom; X represents --CR.sup.3R.sup.4R.sup.5, --NR.sup.6R.sup.7, --(CH.sub.2-CH.dbd.C(CH.sub.3)--CH.sub.2).sub.p--CH.s- ub.2CH.dbd.C(CH.sub.3).sub.2, alkyl, cycloalkyl, phenyl, cinnamyl, or heteroaromatic ring; Y represents --(CH.sub.2).sub.q--, -CH.dbd.CH--, --NR.sup.8--, an oxygen atom, or a bond; z represents carbonyl or a bond; K represents alkylene or a bond; L represents --CH.dbd.CH-- or a bond; and M represents a hydrogen atom, alkyl, cycloalkyl, phenyl, heterocyclic ring, biphenyl, or diphenylmethyl. Excerpt(s): The present invention relates to compounds having inhibitory activity against the biosynthesis of triglycerides and inhibitory activity against the secretion of lipoprotein containing apolipoprotein B, and prophylactic or therapeutic agents for hyperlipidemia comprising the same. A change in eating habits and an increase in the aged population have resulted in increased arteriosclerotic diseases. One of major risk factors of this group of diseases is an abnormal increase in cholesterol or triglycerides (hyperlipidemia). For example, the proportion of familial composite hyperlipidemia (FCHL) in patients suffering from cardiac infarction is about 30% which is higher than other basal diseases, and hyperlipidemia is known to be a basal disease which has a high risk of onset of ischemic heart disease (Lipid, 2, 373 (1991)). Further, hyperlipidemia, which is a complication of obesity or diabetes, has been recognized as a risk factor of arteriosclerosis (Diabetes, 37, 1595(1988) and Int. J. Obesity, 15, 1 (1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel 3-substituted urea derivatives and medicinal use thereof Inventor(s): Ishibuchi, Seigo; (Chuo-ku, Tokyo, JP), Itoh, Katsuhiko; (Saitama-shi, Saitama, JP), Naka, Yoichi; (Nakatsu-shi, Ooita, JP), Sumichika, Hiroshi; (Chuo-ku, Tokyo, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030207939 Date filed: February 5, 2003 Abstract: The present invention relates to a urea derivative of the formula (1) 1wherein each symbol is as described in the specification, a pharmaceutically acceptable salt thereof and pharmaceutical use thereof. The compound of the present invention has a C5a receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of diseases or syndromes due to inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis, pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like]. In addition, it is useful as an agent for the prophylaxis or treatment of infectious diseases caused by bacteria or virus that invades via a C5a receptor.

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Excerpt(s): The present invention relates to a urea derivative showing a C5a receptor antagonistic action and useful for the prophylaxis or treatment of autoimmune diseases such as rheumatism and systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease or serious organ injuries (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like, a pharmaceutically acceptable salt thereof and pharmaceutical use thereof. When the complement system is activated, the protein of the complement system is enzymolysed and fragments having various physiological activities are produced. One of the fragments, complement component C5a, is a glycoprotein having a molecular weight of about 11,000, consists of 74 amino acids and has a strong inflammation inducing action. C5a has a broad range of actions such as smooth muscle contraction, promotion of blood vessel permeability, migration of leukocyte, degranulation of leukocyte, production of reactive oxygen species, reinforcement of antibody production, induction of production of cytokine, TNF (tumor necrosis factor), leukotriene and the like, and the like, and is said to be a causative substance of diseases such as autoimmune diseases (e.g., rheumatism and systemic lupus erythematosus and the like), sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases (e.g., asthma and the like), atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease, serious organ injuries (e.g., pneumonia, nephritis, hepatitis, pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like, and the like [Annu. Rev. Immunol., vol. 12, pp. 775-808 (1994), Immunopharmacology, vol. 38, pp. 3-15 (1997), Curr. Pharm. Des., vol. 5, pp. 737-755 (1999) and IDrugs, vol. 2, pp. 686-693 (1999)]. Accordingly, a non-peptide small molecular compound having a C5a receptor antagonistic action is expected as a novel non-steroid type antiinflammatory drug. In addition, it can be expected as a prophylactic or therapeutic drug of infectious diseases caused by bacteria or virus that invades via a C5a receptor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel human pancreatitis-associated protein Inventor(s): Goli, Surya K.; (San Jose, CA), Hillman, Jennifer L.; (Santa Cruz, CA) Correspondence: Incyte Corporation (formerly Known AS Incyte; Genomics, INC.); 3160 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20030109004 Date filed: December 10, 2002 Abstract: The present invention provides a novel human C-type lectin (human PAP-2) and polynucleotides which identify and encode human PAP-2. The invention also provides expression vectors, host cells, agonists, antibodies or antagonists. The invention also provides methods for treating or preventing diseases associated with expression of human PAP-2. Excerpt(s): This application is a divisional application of U.S. application Ser. No. 09/226,852, filed Jan. 7, 1999, which is a divisional application of U.S. application Ser. No. 08/822,261, filed Mar. 20, 1997, now U.S. Pat. No. 5,935,813, issued Aug. 10, 1999, all of which are entitled NOVEL HUMAN PANCREATITIS-ASSOCIATED PROTEIN, and all of which are hereby incorporated by reference. The present invention relates to

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nucleic acid and amino acid sequences of a novel human pancreatitis-associated (PAP) protein, which comprises a soluble C-type lectin. This novel human PAP protein shares features with other proteins in the reg/PSP multigene family which are involved in the regulation of cell growth. The present invention relates to the use of these novel sequences in the diagnosis, prevention, and treatment of disease. Lectins are proteins which are defined by their ability to bind carbohydrates specifically and to agglutinate cells. Lectins have been shown to be involved in a wide variety of cellular functions, including cell-cell and cell-matrix interactions. Lectins are widespread among plants, invertebrates, and mammals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel inhibitor of beta amyloid cleavage enzyme Inventor(s): Boyd, James G.; (Mystic, CT), Singleton, David H.; (Noank, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020115616 Date filed: February 14, 2002 Excerpt(s): This application claims the benefit of U.S. Serial No. 60/270,006, filed Feb. 20, 2001, the contents of which are incorporated herein by reference. This invention relates to a novel inhibitor of beta amyloid cleavage enzyme (BACE, transmembrane aspartyl protease beta-secretase, beta site APP cleavage enzyme, memapsin-2, BACE-1), pharmaceutical compositions containing it and its use in the treatment of neurological disorders such as Alzheimer's disease, Crutzfield-Jacob's disease, prion disorders, amyotrophic lateral sclerosis, progressive supranuclear palsy, head trauma, stroke, Down's syndrome, pancreatitis, inclusion body myocitis, other peripheral amyloidoses and diabetes. Alzheimer's disease (AD), a progressive neurodegenerative disease of the central nervous system (specifically brain) is characterized by gradual loss of memory, declining orientation skills, motor, sensory, linguistic and cognitive functions of the brain. The pathological indicators of the disease are neurofibrillary tangles and amyloid plaques. These amyloid plaques are unique to AD, however neurofibrillary tangles are associated with many dementia disorders. Beta amyloid peptide (SAP), a highly insoluble peptide 39-43 amino acids in length has a strong propensity to adopt beta sheet structures, oligomerize and form protein aggregates, is a primary component of amyloid plaques. Production of.beta.AP occurs when amyloid polypeptide precursor is cleaved by certain proteases, a group known as secretases. Cleavage by.beta.-secretase at the amino terminus of beta amyloid peptide and cleavage by.gamma.-secretase between residues 39 and 43 (most often at residue 42) constitute the means by which this peptide is produced. Cleavage by.alpha.-secretase (and other metalloproteases) affords a soluble cleavage product by cleaving between residues 16 and 17 of the beta amyloid peptide. This pathway reduces the potential accumulation of.beta.AP by producing a soluble product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Polynucleotides related to pancreatic disease Inventor(s): Kennedy, Giulia; (San Francisco, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. Box 8097; Emeryville; CA; 94662; US Patent Application Number: 20020187507 Date filed: June 6, 2002 Abstract: The present invention is based on the discovery of polynucleotides that represent novel genes that are differentially expressed in pancreatic disease, e.g., pancreatic cancer, dysplasia, pancreatitis, or diabetes. The invention features methods of identifying cells affected by such pancreatic diseases by detection of a gene product encoded by such differentially expressed genes, as well as methods of modulating expression of such gene products to effect therapy (e.g., to decrease growth and/or affect abnormal characteristics of cancerous or dysplastic pancreatic cells.) Excerpt(s): This application claims the benefit of prior U.S. Provisional Application Serial No. 5 60/118,302, filed Feb. 2, 1999, which application is incorporated herein by reference. The invention relates to genes differentially expressed pancreatic disease, in particular, pancreatic cancer, dysplasia, and diabetes. More specifically, it relates to polynucleotides that are differentially regulated in pancreatic cancer and dysplasia. Cancer of the pancreas is the fifth leading cause of cancer death in the United States. According to the American Cancer Society, approximately 28,000 people will die of pancreatic cancer in the United States in 1998. The pancreas is a tongue-shaped glandular organ composed of both endocrine and exocrine gland portions, as well as ducts that connect the pancreas to the bile duct and small intestine. The endocrine portion of the pancreas secretes hormones, such as insulin and glucagon which are involved in blood sugar regulation, into the bloodstream. The exocrine portion of the pancreas produces pancreatic enzymes involved in the digestion of fats and proteins; these enzymes are delivered to the bile duct and into the small intestine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Prodrug of an ice inhibitor Inventor(s): Davies, Robert; (Arlington, MA), Wannamaker, Marion W.; (Stow, MA) Correspondence: Vertex Pharmaceuticals INC.; 130 Waverly Street; Cambridge; MA; 02139-4242; US Patent Application Number: 20020013278 Date filed: May 18, 2001 Abstract: This invention describes an ICE inhibitor prodrug (I) having good bioavailability. 1Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma. Excerpt(s): Pursuant to Title 35, United States Code,.delta. 119 this application claims benefit of U.S. Provisional Application Serial No. 60/205,439, filed May 19, 2000. The

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present invention relates to a novel interleukin-1.beta. converting enzyme (ICE) inhibitor in its prodrug form. The compound and pharmaceutical compositions thereof are useful as agents to treat interleukin-1-(IL-1), apoptosis-, interferon-.gamma. inducing factor-(IL-18), or interferon-.gamma. (IFN-.gamma.) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting ICE activity and decreasing IL-18 production and IFN-.gamma. production and methods for treating interleukin-1, apoptosis-, and interferon-.gamma.mediated diseases using the compositions of this invention. Interleukin-1 (IL-1) is a major pro-inflammatory and immunoregulatory protein that stimulates fibroblast differentiation and proliferation, the production of prostaglandins, collagenase and phospholipase by synovial cells and chondrocytes, basophil and eosinophil degranulation and neutrophil activation. Oppenheim, J. H. et al, Immunology Today, 7, pp. 45-56 (1986). As such, it is involved in the pathogenesis of chronic and acute inflammatory and autoimmune diseases. For example, in rheumatoid arthritis, IL-1 is both a mediator of inflammatory symptoms and of the destruction of the cartilage proteoglycan in afflicted joints. Wood, D. D. et al., Arthritis Rheum. 26, 975, (1983); Pettipher, E. J. et al., Proc. Natl. Acad. Sci. USA 71, 295 (1986); Arend, W. P. and Dayer, J. M., Arthritis Rheum. 38, 151 (1995). IL-1 is also a highly potent bone resorption agent. Jandiski, J. J., J. Oral Path 17, 145 (1988); Dewhirst, F. E. et al., J. Immunol. 8, 2562 1985). It is alternately referred to as "osteoclast activating factor" in destructive bone diseases such as osteoarthritis and multiple myeloma. Bataille, R. et al., Int. J. Clin. Lab. Res. 21(4), 283 (1992). In certain proliferative disorders, such as acute myelogenous leukemia and multiple myeloma, IL-1 can promote tumor cell growth and adhesion. Bani, M. R., J. Natl. Cancer Inst. 83, 123 (1991); Vidal-Vanaclocha, F., Cancer Res. 54, 2667 (1994). In these disorders, IL-1 also stimulates production of other cytokines such as IL-6, which can modulate tumor development (Tartour et al., Cancer Res. 54, p. 6243 (1994). IL-1 is predominantly produced by peripheral blood monocytes as part of the inflammatory response and exists in two distinct agonist forms, IL-1.alpha. and IL-1.beta. Mosely, B. S. et al., Proc. Nat. Acad. Sci., 84, pp. 4572-4576 (1987); Lonnemann, G. et al., Eur. J. Immunol., 19, pp. 1531-1536 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Propanolamine derivatives Inventor(s): Hashimoto, Norio; (Ibaraki-shi, JP), Okamoto, Takumi; (Toyonaka-shi, JP), Sakurai, Minoru; (Toyonaka-shi, JP), Takasugi, Hisashi; (Sakai-shi, JP), Taniguchi, Kiyoshi; (Suma-ku, JP), Tomishima, Yasuyo; (Kita-ku, JP), Tsubaki, Kazunori; (Uji-shi, JP) Correspondence: Oblon Spivak Mcclelland; Maier & Neustadt; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20020006956 Date filed: September 15, 1999 Abstract: This invention relates to new propanolamine derivatives presented by the following formula [I]: 1whereinR.sup.1 is hydrogen or lower alkenyloxy,R.sup.2 is carboxy(lower)alkoxy or protected carboxy(lower)alkoxy,R.sup.3 is hydrogen or Nprotective group,n is an integer of 1 or 2,and salts thereof which have gut selective sympathomimetic, anti-ulcerous, anti-pancreatitis, lipolytic and anti-pollakisuria

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activities, to processes for the preparation thereof and to a pharmaceutical composition comprising the same. Excerpt(s): This invention relates to new propanolamine derivatives and salts thereof which are useful as a medicament. Some propanolamine derivatives having spasmolytic activity and relaxing activity on smooth muscle contraction have known as described, for example, in PCT International Publication WO94/25427. This invention relates to new propanolamine derivatives and salts thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Substituted imidazoles as selective modulators of bradykinin B2 receptors Inventor(s): DeSimone, Robert; (Durham, CT), He, Xiao-shu; (Branford, CT), Hodgetts, Kevin J.; (Killingworth, CT), Hutchison, Alan; (Madison, CT), Maynard, George D.; (Clinton, CT), Rachwal, Stanislaw; (Branford, CT), Shaw, Kenneth; (Weston, CT) Correspondence: Leslie-anne Horvath; Patent Department; Neurogen Corporation; 35 NE Industrial RD.; Branford; CT; 06405; US Patent Application Number: 20020115693 Date filed: January 17, 2001 Abstract: Disclosed are compounds of the formula: 1or the pharmaceutically acceptable non-toxic salts thereof wherein Y, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 R.sub.7' are variables defined herein, which compounds are modulators of Bradykinin B.sub.2 receptors. These compounds are therefore useful in the diagnosis and treatment of renal diseases, heart failure, hypertension, Meniere's disease, vaginal inflammation and pain, peripheral circulatory disorders, climacteric disturbance, retinochoroidal circulatory disorders, myocardial ischemia, myocardial infarction, postmyocardial infarction syndrome, angina pectoris, restenosis after percutaneous transluminal coronary angioplasty, hepatitis, liver cirrhosis, pancreatitis, ileus, diabetes, diabetic complications, male infertility, glaucoma, pain, asthma, and rhinitis, and for the increase of permeability of the blood-brain barrier or the blood-brain-tumor barrier. Excerpt(s): This application claims priority from U.S. provisional patent application no. 60/176,869, filed Jan. 18, 2000. This invention relates to certain imidazoles which, when appropriately substituted, are selective modulators of Bradykinin B.sub.2 receptors (BK2 receptors). This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of central and peripheral disorders. Additionally, compounds of this invention are useful as positive controls in assays for BK-2 receptor activity and when appropriately labeled as probes for the localization of BK-2 receptors in tissue sections. Bradykinin (BK), a nonapeptide, and the closely related decapeptide kallidin (Lys-BK), are produced by proteolytic cleavage of high molecular weight kininogen by plasma kallikreins. The effects of bradykinin and kallidin are mediated by specific seven transmembrane Gprotein coupled receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Sulfide and disulfide compounds and compositions for cholesterol management and related uses Inventor(s): Dasseux, Jean-Louis Henri; (Brighton, MI), Oniciu, Carmen Daniela; (Ann Arbor, MI) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20020077316 Date filed: October 11, 2001 Abstract: The present invention relates to novel sulfide and disulfide compounds, compositions comprising sulfide and disulfide compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising an ether compound. The compounds, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's Disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/239,231, filed Oct. 11, 2000, which is hereby expressly incorporated herein by reference. The present invention relates to sulfide and disulfide compounds; compositions comprising the sulfide or disulfide compounds; and methods for treating or preventing a disease or disorder, for example, cardiovascular disease, dyslipidemia; dyslipoproteinemia; a disorder of glucose metabolism; Alzheimer's Disease; Syndrome X; a peroxisome proliferator activated receptor-associated disorder; septicemia; a thrombotic disorder; obesity; pancreatitis; hypertension; renal disease; cancer; inflammation; and impotence. The compound of the invention can also treat or prevent inflammatory processes and diseases like gastrointestinal disease, irritable bowel syndrome (IBS), inflammatory bowel disease (Crohn's Disease, ulcerative colitis), arthritis (rheumatoid arthritis, osteoarthritis), autoimmune disease (systemic lupus erythematosus, etc.), scleroderma, ankylosing spondylitis, gout and pseudogout, muscle pain: polymyositis/polymyalgia rheumatica/fibrositis; infection and arthritis, juvenile rheumatoid arthritis, tendonitis, bursitis and other soft tissue rheumatism. The sulfide and disulfide compounds and compositions of the invention may also be used to reduce the fat content of meat in livestock and reduce the cholesterol content of eggs. Obesity, hyperlipidemia, and diabetes have been shown to play a causal role in atherosclerotic cardiovascular diseases, which currently account for a considerable proportion of morbidity in Western society. Further, one human disease, termed "Syndrome X" or "Metabolic Syndrome", is manifested by defective glucose metabolism (insulin resistance), elevated blood pressure (hypertension), and a blood lipid imbalance (dyslipidemia). See e.g. Reaven, 1993, Annu. Rev. Med. 44:121-131. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Test system for the determination of in-vivo active hemostasis proteases or of trypsin or subtilisin in biological fluids and/or the usage thereof to determine the in-vivo activation of hemostasis or to diagnose a pancreatitis Inventor(s): Stief, Thomas W.; (Pohlheim, DE) Correspondence: Connolly Bove Lodge & Hutz Llp; 1220 Market Street; P.O. Box 2207; Wilmington; DE; 19899; US Patent Application Number: 20030044876 Date filed: April 2, 2002 Abstract: Test system for the determination of in-vivo active hemostasis proteases or of trypsin or subtilisin in biological fluids and the usage thereof to determine the in-vivo activation of hemostasis or to diagnose a pancreatitis.The present invention describes a global assay of in vivo coagulation activation (GACA), i.e. the global determination of the in vivo activation of hemostasis, particularly of the in vivo activation of coagulation, of biological fluids, particularly of blood and/or plasma and the determination of invivo active trypsin and/or subtilisin. The sample to be tested, preferably a sample anticoagulated with EDTA and/or arginine (or guanidine), is incubated according to the invention with a chromogenic or fluorogenic substrate, particularly for Thrombin and/or Factor Xa and/or other enzymes of hemostasis in presence and/or absence of a contact activator and preferably in presence of EDTA. By detection of the absorbance, fluorescence and/or extinction of samples before and after the incubation the in-vivo activation of hemostasis of the biological fluid or the severity of a pancreatitis is determined. The resulting activity is compared with a known standard and indicated in percent of norm in relation to a 100% normal standard human plasma. The normal range is 100%.+-.50% (mean.+-.2 standard deviations). The GACA-activity of normal human plasma corresponds to a pure standard of 6 mlU/ml Thrombin. Excerpt(s): Test system for the determination of in-vivo active hemostasis proteases or of trypsin or subtilisin in biological fluids and/or the usage thereof to determine the invivo activation of hemostasis or to diagnose a pancreatitis. The present invention relates to a global procedure basing on peptide substrates for the determination of in-vivo active hemostasis proteases or of in-vivo active trypsin or of subtilisin in biological fluids, that particularly can be used to determine the in-vivo activation of hemostasis, particularly of the in-vivo activation of coagulation (GACA) and/or of the contact phase capacity (CPC) of biological fluids or to diagnose a pancreatitis and/or the severity grade of a pancreatitis. Hemostasis is the system of generation and degradation of thrombi, i.e. hemostasis comprises blood coagulation and fibrinolysis. Normally, hemostasis enzymes occur in blood mainly in an inactive form, only a very small part of the respective hemostasis enzymes, that are mainly serine proteases, occur in vivo in an active form, i.e. there is in a very small degree of in vivo activation of hemostasis in the blood of the healthy organism. However, an enhanced in vivo activation of hemostasis is of great pathophysiologic importance in the pathogenesis of many diseases. Consequently, in a pathologically-increased in vivo activation of hemostasis (as in disseminated intravascular coagulation (DIC) or in thrombophilia) more hemostasis enzymes are found in activated form. The determination of this in vivo active hemostasis enzymes, i.e. the determination of the degree of in vivo activation of hemostasis, is of great medical importance for the diagnosis of diseases, that are linked to a changed in vivo activation of hemostasis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of inflammation with 2,4,6-trihydroxy-alpha-para-methoxyphenylacetophenone, or its pharmaceutically acceptable derivatives Inventor(s): Malaviya, Ravi; (St. Paul, MN), Uckun, Fatih M.; (White Bear Lake, MN) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20020010217 Date filed: June 19, 2001 Abstract: 2,4,6-trihydroxy-.alpha.-p-methoxyphenylacetophenone (also identified herein as "D-58"), or its pharmaceutically acceptable derivatives such as salt and ester forms, is administered for inhibiting inflammatory reactions. The treatment can be remedial or prophylactic. Examples of the conditions that can be treated include acute inflammatory reactions and allergic inflammatory reactions, and specific examples include allergy, asthma, arthritis, psoriasis, skin sunburn, inflammatory pelvic disease, inflammatory bowel disease, urethritis, uvitis, senusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, gastritis, enteritis, dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitis and cholangitis. The 2,4,6-trihydroxy.alpha.-p-methoxyphenylacetophenone can be administered by various routes as needed. Excerpt(s): The present invention is directed to the treatment of acute and chronic inflammatory responses, for example resulting from the presence of an allergen, injury, infection, etc. Allergic and acute inflammatory responses to injury, infection, or other tissue damage can set into motion a complex series of events. A variety of host cells that guard the host environment interface, including macrophages, mast cells, and epithelial epidermal cells serve as the initiators of the inflammatory responses. These cells release various mediators during an inflammatory response, which include histamine, prostaglandins (PGs), leukotrienes (LTs) and proinflammatory cytokines (refs 1-4). These mediators have been implicated in the pathogenesis of a number of acute and chronic inflammatory conditions such as allergy, asthma, arthritis, psoriasis, and skin sunburn (refs 3-5). The release of inflammatory agents is mediated by a cascade of intracellular signaling events which include activation of phosphoinositide turnover (ref 6), increase in cAMP levels (ref 7), activation of protein kinase C, and an increase in intracellular calcium levels and tyrosine phosphorylation of several cytosolic proteins (refs 7 and 8). Considerable efforts have been made for identification of chemical compounds that can interrupt these signaling events as potential anti-inflammatory agents (refs 9-12). However, the need for agents providing improved inhibition continues. In accordance with the present invention, 2,4,6-trihydroxy-.alpha.-- pmethoxyphenylacetophenone (also identified herein as "D-58"), or its pharmaceutically acceptable derivatives such as salt and ester forms, is administered for inhibiting inflammatory reactions to a subject in need thereof. The treatment can be remedial or prophylactic. Examples of the conditions that can be treated include acute as well as chronic inflammatory reactions and allergic inflammatory reactions, and specific examples include allergy, asthma, arthritis, psoriasis, skin sunburn, inflammatory pelvic disease, inflammatory bowel disease, urethritis, uvitis, sinusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, gastritis, enteritis, dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitis and cholangititis. The 2,4,6-trihydroxy-.alpha.-p-methoxyphenylacetophenone can be administered by one of a variety of routes as needed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of COX-2 inhibitors to treat sepsis, complications thereof, and EP receptor modulation Inventor(s): Daly, John M.; (Pelham Manor, NY), Mack Strong, Vivian E.; (New York, NY), Stapleton, Philip P.; (New York, NY) Correspondence: Michael L. Goldman, ESQ.; Nixon Peabody Llp; Clinton Square; P.O. Box 31051; Rochester; NY; 14603; US Patent Application Number: 20020006915 Date filed: February 14, 2001 Abstract: The present invention is directed to methods of preventing, inhibiting, reversing and/or ameliorating complications in those having or at risk for systemic inflammatory response syndrome, e.g., sepsis, including multiple organ dysfunction syndrome, pancreatitis, burns, trauma, and complications of sepsis such as bacteremia, pneumonia, urinary tract infections, wound infections, and drug reactions. The methods comprise administration of an effective amount of at least one of a selective inhibitor of cyclooxygenase-2, a drug which stimulates one or more PGE.sub.2 receptors or a drug which interferes with binding of PGE.sub.2 to one of more PGE.sub.2 receptors. Excerpt(s): This application was originally filed as provisional application Ser. No. 60/182,524 on Feb. 15, 2000. The present invention is directed to the prevention and treatment of patients at risk for, or having, systemic inflammatory response syndrome and septic complications. The present invention therefore pertains to treatment of patients in the clinical settings of shock, sepsis, trauma, major elective surgery and critical care. Although numerous studies have demonstrated that injury induces a state of immunosuppression, the precise mechanisms are still under investigation prostaglandin receptors EP2 and EP4 are down regulated and that reversing this down regulation of receptor subtypes markedly improves survival. 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 pancreatitis, 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 “pancreatitis” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on pancreatitis. You can also use this procedure to view pending patent applications concerning pancreatitis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON PANCREATITIS Overview This chapter provides bibliographic book references relating to pancreatitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on pancreatitis include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “pancreatitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on pancreatitis: •

ABC of Liver, Pancreas and Gall Bladder Source: London, UK: BMJ Publishing Group. 2001. 54 p. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. ISBN: 0727915312. Summary: Diseases of the liver, pancreas, and biliary system affect a substantial proportion of the world's population and involve doctors and health care workers across many disciplines. Many of these disease produce great misery and distress and are economically important requiring much time off work. This atlas of the liver, pancreas and gallbladder provides an overview of these diseases and enable the busy clinician to keep abreast of advances in diagnosis and management of not only the common but also the rarer, but none the less important, conditions. The atlas includes fourteen chapters: investigation of liver and biliary disease, gallstone disease, acute

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hepatitis, chronic viral hepatitis, other causes of parenchymal liver disease, portal hypertension and ascites, portal hypertension and encephalopathy, liver tumors, liver abscesses and hydatid disease, acute pancreatitis, chronic pancreatitis, pancreatic tumors, liver and pancreatic trauma, and transplantation of the liver and pancreas. Each chapter covers the symptoms, diagnosis, etiology, natural course, and treatment of the disease under consideration. Each chapter is illustrated with full-color diagrams, charts, and clinical photographs. A subject index concludes the book. •

Hepatobiliary and Pancreatic Disease: The Team Approach to Management Source: Boston, MA: Little, Brown and Company. 1995. 493 p. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail: [email protected]. Website: http://www.lrpub.com. PRICE: $99.95. ISBN: 0316709158. Summary: In this book, the editors identify 42 hepatobiliary and pancreatic problems that require a team approach to management. For each of the 42 chapters, a surgeon, gastroenterologist, or radiologist is the lead author, and physicians from different specialties are coauthors. The authors discuss etiology, pathogenesis, and diagnosis, but focus on patient management and results. The chapters cover hepatitis, hepatic failure, cirrhosis, portal hypertension, primary biliary cirrhosis, Budd-Chiari syndrome, noninflammatory cysts, hepatic abscesses, hydatid disease, hemobilia, hepatic trauma, benign hepatic tumors, hepatocellular carcinoma, hepatic metastases, biliary atresia, biliary cysts, gallbladder stones, choledocholithiasis, hepatolithiasis, acute cholecystitis, acute cholangitis, biliary parasites, sclerosing cholangitis, benign strictures, motility disorders, gallbladder cancer, cholangiocarcinoma, acute pancreatitis, gallstone pancreatitis, pseudocysts, pancreatic abscesses, pancreatic necrosis, pancreatic hemorrhage, pancreas divisum, chronic pancreatitis, pancreatic fistulas, pancreatic trauma, islet cell tumors, cystic neoplasms, ampullary carcinoma, and pancreatic cancer. Each chapter includes numerous black-and-white photographs, and a subject index concludes the volume.

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Gastroenterology and Hepatology: The Comprehensive Visual Reference. Volume 8: Pancreas Source: Philadelphia, PA: Current Medicine. 1998. [200 p.]. Contact: Available from Current Medicine. 400 Market Street, Suite 700, Philadelphia, PA 19106. (800) 427-1796 or (215) 574-2266. Fax (215) 574-2270. E-mail: [email protected]. Website: current-medicine.com. PRICE: $125.00 plus shipping and handling. ISBN: 0443078629. Summary: This atlas is one in an 8-volume collection of images that pictorially displays the gastrointestinal tract, liver, biliary tree, and pancreas in health and disease, both in children and adults. This volume includes 10 chapters on the pancreas. Topics covered include neurohormonal control of the pancreas, pathogenesis of pancreatic diseases, acute pancreatitis, chronic pancreatitis, surgery for chronic pancreatitis, developmental anomalies of the pancreas, pancreatic cancer, the rationale and application of radioligand imaging in gastroenterology, cystic fibrosis, and hereditary pancreatitis. The format of the atlas is visual images supported by relatively brief text. Tables, charts, diagrams, and photomicrographs are used extensively. A subject index concludes the volume.

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Evidence Based Gastroenterology and Hepatology Source: London, UK: BMJ Publishing Group. 1999. 557 p. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. ISBN: 0727911821. Summary: This book emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The authors use clinical epidemiology to present the strongest and most current evidence for interventions for the major diseases of the gastrointestinal tract and liver. Thirty chapters are included: an introduction to evidence based gastroenterology and hepatology; gastroesophageal reflux disease (GERD); ulcer disease and Helicobacter pylori; ulcer disease and nonsteroidal antiinflammatory drugs; treatment options for non-variceal gastrointestinal hemorrhage; the diagnosis and treatment of functional dyspepsia (indigestion); the diagnosis, treatment, and prognosis of celiac disease (gluten intolerance); the treatment of Crohn's disease; the diagnosis, prognosis, and treatment of ulcerative colitis (UC); pouchitis after restorative proctocolectomy; metabolic bone disease in gastrointestinal disorders; colorectal cancer in UC and the role of surveillance; population based screening and surveillance for colorectal cancer; irritable bowel syndrome (IBS); the surgical treatment of gallstone disease; the prognosis and treatment of acute pancreatitis; hepatitis C; hepatitis B; the screening and treatment of alcoholic liver disease; hemochromatosis and Wilson disease; primary biliary cirrhosis (PBC); autoimmune hepatitis; primary sclerosing cholangitis (PSC); the prevention and treatment of portal hypertensive bleeding; ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis; hepatic encephalopathy; hepatocellular carcinoma; fulminant hepatic failure; the prevention and treatment of rejection after liver transplantation; and the prevention and treatment of infection after liver transplantation. Each chapter features the grading of recommendations and levels of evidence used by the authors to note the research basis on which their clinical guidelines are formed. Chapters conclude with extensive reference lists; the text concludes with a subject index. A glossary of acronyms is also provided.

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Gastrointestinal and Hepatobiliary Pathophysiology Source: Madison, CT: Fence Creek Publishing. 1998. 475 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Malden, MA 02148. (800) 215-1000 or (781) 388-8250. Fax (781) 388-8270. E-mail: [email protected]. Website: www.blackwellscience.com. PRICE: $27.95 plus shipping and handling. ISBN: 1889325015. Summary: This book on gastrointestinal and hepatobiliary pathophysiology is one from a series designed to meet the second and third year medical students' needs for a concise but comprehensive resource that focuses on organ system pathophysiology. The test covers the pathogenesis, diagnosis, treatment, and management of common diseases, using a format that includes one or more clinical cases integrated throughout the chapters to foster direct application of clinical problem solving skills; extensive use of margin notes that concisely highlight important concepts, define key terms, and pinpoint clinical correlations; questions at the end of each chapter, using the NBME format, that offer a means for accurate self assessment; and wide margins to accommodate note taking by students as they study. Thirty chapters cover an overview of gastrointestinal and hepatobiliary function; regulation of the digestive system; the

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anatomy, histology, and embryology of the gastrointestinal tract; an overview of gastrointestinal motility; gastrointestinal electrolyte and fluid secretion; digestion and absorption; management of water and electrolytes; liver anatomy and physiology; liver metabolism, physiology of bile formation, and gallstones; normal and disordered swallowing; peptic ulcer disease; small bowel disorders; acute and chronic pancreatitis; functional bowel disorders; the mucosal immune system; inflammatory bowel disease; infectious disorders of the gastrointestinal tract; viral hepatitis; hereditary liver disease; autoimmune liver disease; pathogenesis and consequences of portal hypertension; disorders of cholestasis, bilirubin metabolism, and jaundice; orthotopic liver transplantation; alcohol and the gastrointestinal tract; the pathophysiology of abdominal pain and pain syndromes; gastrointestinal disorders in pregnancy; the molecular biology of gastrointestinal malignancies and overview of neoplasms of the gastrointestinal tract; pharmacology; principles of nutritional support in the gastrointestinal patient; and gastrointestinal bleeding. A subject index concludes the textbook. •

Good Food for Bad Stomachs Source: New York, NY: Oxford University Press. 1997. 240 p. Contact: Available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $12.95 plus shipping and handling. ISBN: 0195126556. Summary: This book presents a detailed look at present knowledge about the role of eating habits in preventing, causing, and treating the many disorders that plague the gastrointestinal tract and its associated digestive glands, the liver, the gallbladder, and the pancreas. The author begins with three chapters that discuss nutrition and digestion, focusing on the elements of a realistic, reasonable diet. Other portions of the book are devoted to intestinal gas, constipation, diarrhea, the effect of aging, the effects of food on drug absorption, and the many effects of drugs on food absorption. The bulk of the chapters treat the kinds of disorders that can and do occur from one end of the digestive tract to the other, and the role of diet in these disorders. The author covers esophagitis, swallowing disorders, inflammation and ulcers of the stomach and duodenum (including peptic ulcer and gastritis), gallstones, pancreatitis, acute and chronic liver disease, traveler's diarrhea, constipation, inflammation and defects of the small intestine, celiac disease (gluten enteropathy), kidney oxalate stones, and the role of diet in colonic polyps and colon and rectal cancer. The author also discusses food intolerances, allergies, and reactions. The book concludes with a subject index. 14 tables.

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Surgical Management of the Diabetic Patient Source: New York, NY: Raven Press. 1991. 425 p. Contact: Available from Raven Press. 1185 Avenue of the Americas, Dept. 5B, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Fax (212) 869-3495. PRICE: $105 plus shipping (as of 1995). ISBN: 0881677205. Summary: This book provides practical information for the detailed assessment of the patient with diabetes, from the early stages when surgery is first considered, through the surgical and postsurgical periods as well. Twenty-nine chapters authored by specialists in diabetes care cover topics including carbohydrate metabolism and other nutritional considerations; surgery in diabetic nephropathy; cardiovascular disease and hypertension; syndromes of infection; emergency surgery considerations; diabetic neuropathy; pancreatitis; pediatric and adolescent patients; foot care and management;

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gastrointestinal surgery; urologic complications; renal transplantation; diabetes and pregnancy; surgery for obesity; and surgery in the patient with diabetic eye disease. Each chapter includes numerous references. A detailed subject index is appended. •

Mayo Clinic on Digestive Health Source: Rochester, MN: Mayo Clinic. 2000. 194 p. Contact: Available from Mayo Clinic Health Information. 5505 36th Street, SE, Grand Rapids, MI 49512. (800) 291-1128. Website: www.mayoclinic.com. PRICE: $14.95 plus shipping and handling. ISBN: 1893005046. Summary: This comprehensive guidebook from the Mayo Clinic focuses on a variety of digestive symptoms, including heartburn, abdominal pain, constipation, and diarrhea, and the common conditions that are often responsible for these symptoms. Written in nontechnical language, the book includes practical information on how the digestive system works, factors that can interfere with its normal functioning, and how to prevent digestive problems. After two introductory chapters in which the authors review the anatomy and physiology of the digestive tract and practical suggestions for maintaining a healthy digestive tract, the book includes 12 chapters on symptoms, common diagnostic tests, gastroesophageal reflux disease (GERD), ulcers and stomach pain, irritable bowel syndrome, Crohn's disease and ulcerative colitis (together called inflammatory bowel disease or IBD), celiac disease, diverticular disease, gallstones, pancreatitis, liver disease, and cancer. Each chapter on a specific condition reviews the symptoms, diagnosis, risk factors, prognosis, and treatment options for that condition. The book concludes with a list of resource organizations through which readers can obtain more information, and a subject index.

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Clinical Practice of Gastroenterology. Volume Two Source: Philadelphia, PA: Current Medicine. 1999. 861 p. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: This lengthy textbook brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. This second volume includes 113 chapters in five sections: liver, gallbladder and biliary tract, pancreas, pediatric gastroenterology, and special topics. Specific topics include hepatic (liver) structure and function, jaundice, viral hepatitis, alcoholic liver injury, liver tumors, parasitic diseases of the liver, Wilson's disease, hemochromatosis, the pregnancy patient with liver disease, portal hypertension, hepatic encephalopathy, fulminant hepatic failure, liver transplantation, the anatomy of the gallbladder and biliary tract, gallstones, laparoscopic cholecystectomy (gallbladder removal), cholecystitis (gallbladder infection), primary sclerosing cholangitis, biliary obstruction, pancreatic anatomy and physiology, acute pancreatitis, pancreatic fistulas and ascites (fluid accumulation), chronic pancreatitis, cancer of the pancreas, endoscopic retrograde cholangiopancreatography, esophageal atresia, gastroesophageal reflux in infants and children, achalasia and esophageal motility disorders, caustic and foreign body ingestion, vomiting, chronic abdominal pain, gastritis and peptic ulcer disease in children, malabsorption syndromes in children, inflammatory bowel disease in children and adolescents, acute appendicitis, cystic fibrosis, constipation and fecal soiling (incontinence), hepatitis in children, liver transplantation in children, failure to thrive,

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pediatric AIDS, the gastrointestinal manifestations of AIDS, the evaluation and management of acute upper gastrointestinal bleeding, principles of endoscopy, eating disorders, nutritional assessment, enteral and parenteral nutrition, gastrointestinal diseases in the elderly and in pregnancy, nosocomial infections, and the psychosocial aspects of gastroenterology (doctor patient interactions). The chapters include figures, algorithms, charts, graphs, radiographs, endoscopic pictures, intraoperative photographs, photomicrographs, tables, and extensive references. The volume concludes with a detailed subject index and a section of color plates. •

Alcohol and the Gastrointestinal Tract Source: Boca Raton, FL: CRC Press. 1996. 347 p. Contact: Available from CRC Press. 2000 Corporate Boulevard NW., Boca Raton, FL 33431. (800) 272-7737 or (561) 994-0555. Fax (800) 374-3401. E-mail: [email protected]. Website: http://www.crcpress.com. PRICE: $179.00. ISBN: 0849324807. Summary: This medical text considers alcohol and the gastrointestinal tract. The topics include the metabolism of alcohol and its implications for the pathogenesis of disease; endocrine changes in alcoholism with special reference to GI hormones; the effects of ethanol on salivary glands; alcoholic pancreatitis; small bowel injury by ethanol; alcohol-induced malabsorption in the GI tract; alcohol and small intestinal permeability; GI motility disorders induced by ethanol; lipid metabolism in the intestinal tract and its modification by ethanol; alcohol's promotion of GI carcinogenesis; and objectives for future research in understanding the effects of ethanol on the GI tract. A subject index concludes the book.

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Pediatric Gastrointestinal Disease. 2nd ed Source: Philadelphia, PA: W.B. Saunders Company. 1999. 823 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522 or (314) 4537010. Fax (800) 568-5136 or (314) 453-7095. E-mail: [email protected]. Website: customerservice.wbsaunders.com. PRICE: $155.00 plus shipping and handling. ISBN: 0721674615. Summary: This medical textbook covers all facets of clinical pediatric gastrointestinal disease. The text emphasizes a clinical focus and incorporates anatomy and physiology considerations into each chapter rather than a separate section. The book is organized into distinct sections, starting with the common clinical problems and followed by organ specific diseases. General chapters on clinical problems cover chronic abdominal pain of childhood and adolescence, vomiting, diarrhea, constipation and encopresis (fecal soiling), failure to thrive, gastrointestinal hemorrhage, eating disorders and obesity, jaundice, ascites, caustic ingestion and foreign bodies, abdominal masses in pediatric patients, and abdominal surgical emergencies. Sections on diseases of the esophagus, stomach, and the small and large bowel (intestine) are followed by chapters reviewing the clinical facets of pediatric liver disease. Specific chapters include gastrointestinal reflux, achalasia and other motor disorders, congenital anomalies, gastric motility disorders, bezoars (a mass of food, hair or other components found in the stomach or intestine), maldigestion and malabsorption, celiac disease, short bowel syndrome, enteric parasites, Crohn's disease, ulcerative colitis, polyps, appendicitis, hernia, Hirschsprung's disease, neoplasms (cancerous and noncancerous), hepatitis, gallbladder diseases, and liver transplantation. The last two sections review diseases of the pancreas and basic nutrition in children, including pancreatitis, cystic fibrosis, nutritional

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assessment, parenteral (outside the digestive system, for example, intravenous nutrition) and enteral nutrition, and the management of diarrhea. Each chapter offers black and white photographs and figures and concludes with extensive references. A detailed subject index concludes the text. •

Office Management of Digestive Diseases Source: Malvern, PA: Lea and Febiger. 1992. 246 p. Contact: Available from Lea and Febiger. Box 3024, Malvern, PA 19355-9725. (215) 2512230. PRICE: $39.50. ISBN: 0812114361. Summary: This medical textbook presents information for primary care physicians dealing with the office management of common gastrointestinal diseases. Twenty-one chapters, each written by experts in the field, cover reflux esophagitis, dysphagia, peptic ulcer disease, chronic abdominal pain, diarrhea, diverticular disease, inflammatory bowel disease, colonic neoplasms, flexible sigmoidoscopy, chronic pancreatitis, irritable bowel syndrome, gallstones, hepatitis, cirrhosis, perianal diseases, premalignant gastrointestinal lesions, liver chemistry abnormalities, and flexible endoscopy. Each chapter includes numerous references and a subject index concludes the volume.

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Pediatric Clinical Gastroenterology. 4th ed Source: St. Louis, MO: Mosby-Year Book, Inc. 1995. 1065 p. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive. St. Louis, MO 63146. (800) 426-4545 or (800) 325-4177 or (314) 872-8370. Fax (314) 432-1380. PRICE: $100 (as of 1995). ISBN: 0815174063. Summary: This textbook of pediatric clinical gastroenterology presents 37 chapters in 5 sections: symptoms and signs; diseases of the gastrointestinal tract; diseases of the liver; diseases of the pancreas; and nutritional support. Specific topics include gastrointestinal (GI) emergencies of the neonate; intestinal obstruction; sucking and swallowing disorders; diseases of the esophagus; disorders of the stomach and duodenum; diarrheal disorders; carbohydrate intolerance; malabsorption syndrome; protein losing gastroenteropathy; immune homeostasis and the gut; inflammatory bowel diseases; constipation, fecal incontinence, and proctologic conditions; functional recurrent abdominal pain; parasitic and fungal disease of the GI tract; neonatal unconjugated hyperbilirubinemias; neonatal hepatitis; prolonged obstructive jaundice; acute and chronic viral hepatitis; bacterial, rickettsial, and parasitic infections and infestations; fulminant hepatic failure and hepatic coma; cirrhosis; portal hypertension; inborn errors of metabolism; hepatic tumors; liver transplantation; congenital anomalies and heredity disorders; cystic fibrosis; pancreatitis and pancreatic tumors; energy and nutrient requirements; infant feeding; and enteral and parenteral alimentation. Each chapter includes numerous references and a subject index concludes the volume.

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Drug Therapy for Gastrointestinal and Liver Diseases Source: Florence, KY: Martin Dunitz. 2001. 352 p. Contact:.AV.-Available from Martin Dunitz. Fulfillment Center, Taylor and Francis, 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. E-mail: cserve@routledge_ny.com. Website: www.dunitz.co.uk. PRICE: $75.00 plus shipping and handling. ISBN: 1853177334.

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Summary: This textbook reviews the drug therapy for gastrointestinal and liver diseases. Fifteen chapters cover drug therapy of gastroesophageal reflux disease (GERD), peptic ulcer disease, emesis (vomiting), gastrointestinal bleeding, inflammatory bowel disease, gastrointestinal and liver infections, motility disorders, functional abdominal disorders, gastrointestinal cancer, pancreatitis and pancreatic insufficiency, viral hepatitis, non-viral liver disease, drug therapy for portal hypertension, hepatic (liver) failure, and the adverse effects of drugs on the gastrointestinal tract. Each chapter provides a brief summary of the pathophysiology of the disease, the rationale for drug intervention, and appropriate treatment regimens as indicated by current knowledge. Also includes is a drug list that summarizes mode of action, and other aspects of clinical pharmacology where appropriate, drug doses, common adverse affects, and drug interactions. A subject index concludes the volume.

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 “pancreatitis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “pancreatitis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “pancreatitis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Primer of Pancreatitis by Paul Georg Lankisch (Editor), et al (1997); ISBN: 354063259X; http://www.amazon.com/exec/obidos/ASIN/354063259X/icongroupinterna

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Acute Pancreatitis by G. Glazer; ISBN: 0702012483; http://www.amazon.com/exec/obidos/ASIN/0702012483/icongroupinterna

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Acute Pancreatitis, Part I (1993); ISBN: 094581223X; http://www.amazon.com/exec/obidos/ASIN/094581223X/icongroupinterna

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Acute Pancreatitis: An Interdisciplinary Synopsis by L. F. Hollender; ISBN: 0806708417; http://www.amazon.com/exec/obidos/ASIN/0806708417/icongroupinterna

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Acute Pancreatitis: An Overview (Critical Care Nurse) by Susan L. Smith, Rebecca Wills Butler; ISBN: 0840386737; http://www.amazon.com/exec/obidos/ASIN/0840386737/icongroupinterna

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Acute Pancreatitis: Diagnosis and Therapy by Edward L., Iii, M.D. Bradley (Editor); ISBN: 0781700914; http://www.amazon.com/exec/obidos/ASIN/0781700914/icongroupinterna

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Acute Pancreatitis: Research and Clinical Management by H. Beger (Editor); ISBN: 3540175342; http://www.amazon.com/exec/obidos/ASIN/3540175342/icongroupinterna

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Acute Pancreatitis:: Novel Concepts in Biology and Therapy by Markus Buchler, et al (1999); ISBN: 0632053399; http://www.amazon.com/exec/obidos/ASIN/0632053399/icongroupinterna

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Chronic Pancreatitis by Eugene P. Dimagno (Editor), Alberto Maringhini (Editor) (1999); ISBN: 9810234406; http://www.amazon.com/exec/obidos/ASIN/9810234406/icongroupinterna

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Chronic Pancreatitis by Buechler; ISBN: 0632063998; http://www.amazon.com/exec/obidos/ASIN/0632063998/icongroupinterna

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Chronic Pancreatitis: An Interdisciplinary Approach by N. Soehendra (Editor), et al (1997); ISBN: 3110152312; http://www.amazon.com/exec/obidos/ASIN/3110152312/icongroupinterna

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Chronic Pancreatitis: Research and Clinical Management by H. G. Beger (1990); ISBN: 3540520341; http://www.amazon.com/exec/obidos/ASIN/3540520341/icongroupinterna

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Complications of Pancreatitis: Medical and Surgical Management by Edward L Bradley; ISBN: 072161907X; http://www.amazon.com/exec/obidos/ASIN/072161907X/icongroupinterna

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Controversies in Acute Pancreatitis by L. F. Hollender; ISBN: 0387114106; http://www.amazon.com/exec/obidos/ASIN/0387114106/icongroupinterna

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Diseases of the Pancreas: Acute Pancreatitis, Chronic Pancreatitis, Tumours of the Pancreas by Markus Buchler, et al (2003); ISBN: 3805576137; http://www.amazon.com/exec/obidos/ASIN/3805576137/icongroupinterna

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Dogs, Diet, & Disease: An Owner's Guide to Diabetes Mellitus, Pancreatitis, Cushing's Disease, & More by Caroline D. Levin; ISBN: 0967225329; http://www.amazon.com/exec/obidos/ASIN/0967225329/icongroupinterna

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Pancreatitis by Peter A. Banks, Paul G. Lankisch (Contributor) (1998); ISBN: 3540617264; http://www.amazon.com/exec/obidos/ASIN/3540617264/icongroupinterna

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Pancreatitis by Earl Edward Gambill; ISBN: 0801617219; http://www.amazon.com/exec/obidos/ASIN/0801617219/icongroupinterna

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Pancreatitis by Daniel Paloyan; ISBN: 0874885701; http://www.amazon.com/exec/obidos/ASIN/0874885701/icongroupinterna

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Pancreatitis; ISBN: 413068115X; http://www.amazon.com/exec/obidos/ASIN/413068115X/icongroupinterna

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Pancreatitis (Clinical Surgery International, Vol 16) by David C. Carter (Editor), Andrew L. Warshaw (Editor) (1989); ISBN: 0443037922; http://www.amazon.com/exec/obidos/ASIN/0443037922/icongroupinterna

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Pancreatitis (SuDoc HE 20.3323:P 19) by U.S. Dept of Health and Human Services; ISBN: B000108Z6A; http://www.amazon.com/exec/obidos/ASIN/B000108Z6A/icongroupinterna

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Pancreatitis and Its Complications (Clinical Gastroenterology) by Christopher E. Forsmark (Editor) (2004); ISBN: 1588291790; http://www.amazon.com/exec/obidos/ASIN/1588291790/icongroupinterna

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Pancreatitis: Concepts and Classification (International Congress Series, No 642) by H. Sarles (Editor), et al; ISBN: 0444806504; http://www.amazon.com/exec/obidos/ASIN/0444806504/icongroupinterna

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Pancreatitis: Its Pathophysiology and Clinical Aspects (Japan Intractable Diseases Research Foundation Publication, No 24) by Toshio Sato, Hidemi Yamauchi (Editor);

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ISBN: 0860083918; http://www.amazon.com/exec/obidos/ASIN/0860083918/icongroupinterna •

Pathogenesis of Pancreatitis: Based on a Symposium Held on 15 November 1990 at the University of Manchester Under the Auspices of the Pancreatic Soc by Joan M. Braganza (Editor) (1991); ISBN: 0719034809; http://www.amazon.com/exec/obidos/ASIN/0719034809/icongroupinterna

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Standards in Experimental Acute Pancreatitis (European Surgical Research, Vol24, Supplement No 1) by M. Buchler, H.G. Beger (Editor) (1992); ISBN: 3805555717; http://www.amazon.com/exec/obidos/ASIN/3805555717/icongroupinterna

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Surgical Treatment of Chronic Pancreatitis - New Standards (Journal - Digestive Surgery , Vol 13, No 2) by M.W. Buchler (Editor), et al (1996); ISBN: 380556323X; http://www.amazon.com/exec/obidos/ASIN/380556323X/icongroupinterna

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The Official Patient's Sourcebook on Pancreatitis: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597834008; http://www.amazon.com/exec/obidos/ASIN/0597834008/icongroupinterna

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The Open Packing - Laparostomy: In Pancreatitis and Peritonitis; ISBN: 354052276X; http://www.amazon.com/exec/obidos/ASIN/354052276X/icongroupinterna

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The Open Packing-Laparostomy-In Pancreatitis and Peritonitis by H.W. Waclawiczek, et al; ISBN: 038752276X; http://www.amazon.com/exec/obidos/ASIN/038752276X/icongroupinterna

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Topics in acute and chronic pancreatitis; ISBN: 0387104399; http://www.amazon.com/exec/obidos/ASIN/0387104399/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “pancreatitis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Acute and chronic pancreatitis Author: Toskes, Phillip P. (Phillip Paul),; Year: 1969; Chicago: Year Book Medical Publishers, c1983

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Acute and subacute interstitial pancreatitis. Author: Evans, Harold Warren,; Year: 1965; [Minneapolis] 1957

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Acute experimental pancreatitis of the rat: with special reference to proteolytic enzymes and proteinase inhibitors Author: Huttunen, Risto.; Year: 1968; Oulu: Univ. of Oulu, 1974; ISBN: 9514202082

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Acute pancreatitis Author: Ranson, John H. C. (John Hugh Charles),; Year: 1970; Chicago: Year Book Medical Publishers, c1979; ISBN: 0815199031 http://www.amazon.com/exec/obidos/ASIN/0815199031/icongroupinterna

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Acute pancreatitis, by Marvin L. Gliedman, Hooshang Bolooki [and] Richard G. Rosen. Author: Gliedman, Marvin L.,; Year: 1963; Chicago, Year Book Medical Publishers, 1970

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Alcohol consumption and acute pancreatitis in men [by] Lars Kager, Staffan Lindberg [and] Gunnar Aagren. Author: Kager, Lars.; Year: 1962; Oslo, Universitetsforlaget [1972]

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Angiography in acute experimental pancreatitis correlated to hemodynamic changes Author: Skjennald, Arnulf.; Year: 1967; Oslo, Norway; Irvington-on-Hudson, N.Y.: Universitetsforlaget, 1982

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Chronic pancreatitis and multiple sclerosis. Author: Evans, Emrys Peregryn.; Year: 1972; [Winnipeg, 1955]

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Chronic recurrent pancreatitis and pancreatic pseudocysts [by] M. P. Mercadier, J. P. Clot [and] T. R. Russell. Author: Mercadier, M. P.; Year: 1963; Chicago, Year Book Medical Publishers, 1973; ISBN: 0815199031 http://www.amazon.com/exec/obidos/ASIN/0815199031/icongroupinterna

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Diagnostic criteria, classification, and clinical course in pancreatitis Author: Seligson, Ulf.; Year: 1970; Stockholm: [s.n.]: Distributed by Almqvist; Wiksell, 1982

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Experimental biliary pancreatitis in dogs. Demonstration of proteolytic activity in pancreatic tissue extracts and interference of dog serum constituents with proteolytic enzymes. Author: Herva, Paavo.; Year: 1971; Oslo, Universitetsforlaget [1970]

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Fat necrosis in acute pancreatitis; morphology and chemical studies in the rat. Author: Storck, Gunnar.; Year: 1967; Stockholm, 1971

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Fat necrosis; studies in rats with experimentally induced pancreatitis. Author: Theve, N. O.; Year: 1966; Stockholm, 1972

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Pancreatitis Author: Banks, Peter A.; Year: 1972; New York: Plenum Medical Book Co., c1979; ISBN: 0306401169 http://www.amazon.com/exec/obidos/ASIN/0306401169/icongroupinterna

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Pancreatitis [by] Henry D. Janowitz [and] David A. Dreiling. Author: Janowitz, Henry D.; Year: 1960; [Chicago, Year Book Publishers, 1959]

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Pancreatitis. Author: White, Thomas Taylor,; Year: 1968; London, Arnold [1966]

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Pancreatitis; a clinical-pathologic correlation, by Herman T. Blumenthal and J. G. Probstein. Author: Blumenthal, Herman Theodore,; Year: 1964; Springfield, Thomas [c1959]

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Surgery for chronic pancreatitis Author: Nardi, George L. (George Lionel),; Year: 1972; Boston: Little, Brown, 1977

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The efficacy of intraductal infusions of mixed bile and pancreatic juice in producing pancreatitis in the dog. Author: Joyeuse, René.; Year: 1972; [Minneapolis] 1961

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The forms of pancreatitis. Author: Paloyan, Edward,; Year: 1965; Chicago, Year Book Medical Publishers, 1967

Chapters on Pancreatitis In order to find chapters that specifically relate to pancreatitis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search

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to book chapters and pancreatitis using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “pancreatitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on pancreatitis: •

Pancreatitis and Pancreatic Insufficiency Source: in Farthing, M.J.G.; Ballinger, A.B., eds. Drug Therapy for Gastrointestinal and Liver Diseases. Florence, KY: Martin Dunitz. 2001. p. 221-233. Contact: Available from Martin Dunitz. Fulfillment Center, Taylor and Francis, 7625 Empire Drive, Florence, KY 41042. (800) 634-7064. E-mail: cserve@routledge_ny.com. Website: www.dunitz.co.uk. PRICE: $75.00 plus shipping and handling. ISBN: 1853177334. Summary: This chapter on pancreatitis and pancreatic insufficiency is from a textbook that reviews the drug therapy for gastrointestinal and liver diseases. Disorders covered include acute pancreatitis, chronic pancreatitis, exocrine insufficiency, endocrine insufficiency (diabetes mellitus), pseudocysts, and pancreatic fistula. The chapter provides a brief summary of the pathophysiology of each disease, the rationale for drug intervention, and appropriate treatment regimens as indicated by current knowledge. The chapter concludes with a drug list that summarizes mode of action, and other aspects of clinical pharmacology where appropriate, drug doses, common adverse affects, and drug interactions. 1 figure. 3 tables. 73 references.

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Pancreatitis in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 329-332. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on pancreatitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and Ulcerative Colitis (UC), together known as inflammatory bowel disease (IBD). There is a higher incidence and prevalence of pancreatitis in patients with inflammatory bowel disease (IBD) than in the general population. The pancreatitis can be acute or chronic, or subclinical or overt, and has many causes. The most common cause is medications used to treat IBD, especially azathioprine and 6 mercaptopurine. Other causes of pancreatitis include duodenal involvement from Crohn's disease (CD), gallstones (cholelithiasis), and primary sclerosing cholangitis (PSC). Pancreatitis also can be caused by high serum concentrations of triglycerides during total parenteral nutritional (TPN) therapy for CD, and may also be a primary extra-intestinal manifestation of IBD. Treatment is different for each cause. For drug-induced pancreatitis, discontinuation of the drug should improvethe pancreatitis. For TPNinduced pancreatitis, oral medium-chain triglycerides should be substituted for the lipid emulsion. For pancreatitis that has developed from gallstones, the usual treatment is laparoscopic cholecystectomy (removal of the gallbladder). Idiopathic (of unknown cause) pancreatitis is often successfully treated by treating the underlying IBD. 1 table. 10 references.

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Acute Pancreatitis: Prognosis and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 271293. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. Summary: This chapter on the prognosis and treatment of acute pancreatitis is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The authors of this chapter review the evidence available from the literature that examines the use of various prognostic instruments and the medical, surgical, and endoscopic treatment options available for acute pancreatitis. Most patients with acute pancreatitis will have a mild form and ultimately follow a benign clinical course, but up to 20 percent will develop severe pancreatitis with all its inherent morbidity (illness) and risk of mortality (death). Medical management remains the mainstay of treatment for patients with acute pancreatitis. Early reduction in the systemic response to pancreatitis might be achieved with drug therapy, but this has not been proven to be effective with the medications presently available. Antibiotic prophylaxis is likely to become part of the standard therapy for those with necrotizing pancreatitis. While total parenteral nutrition (TPN) is of little benefit for those with severe pancreatitis, early enteral feeding shows promise and should become the standard method of nutritional supplementation in these patients. The role of peritoneal lavage (washing out of the organ or peritoneal cavity) remains controversial and the patient population that may benefit from this intervention is not well defined. The surgical approach still remains controversial but, based on the evidence available, widespread necrosectomy (removal of the dead tissue) and lavage, or necrosectomy and open management probably results in a better overall outcome than the conventional surgical approach. 10 tables. 123 references.

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Diagnosis and Management of Chronic Pancreatitis Source: in Danzi, J.T.; Scopelliti, J.A., eds. Office Management of Digestive Diseases. Malvern, PA: Lea and Febiger. 1992. p. 95-101. Contact: Available from Lea and Febiger. Box 3024, Malvern, PA 19355-9725. (215) 2512230. PRICE: $39.50. ISBN: 0812114361. Summary: This chapter, from a medical textbook about the office management of common gastrointestinal diseases, discusses the diagnosis and management of chronic pancreatitis. The author notes that the clinical presentation of chronic pancreatitis varies according to the stage of the disease and the amount of destruction of the exocrine and endocrine components of the gland. Topics include the pathogenesis of pancreatitis, including alcohol-related pancreatitis, diagnostic considerations, the metabolic diseases associated with chronic pancreatitis, screening tests and indicators of chronic pancreatitis, and the management of three main complications of chronic pancreatitis: insulin-dependent diabetes, cyst formation, and steatorrhea. 1 figure. 1 table. 14 references.

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CHAPTER 8. MULTIMEDIA ON PANCREATITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on pancreatitis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on pancreatitis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “pancreatitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “pancreatitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on pancreatitis: •

Goodbye Gallstones Source: Madison, WI: University of Wisconsin Hospitals and Clinics, Department of Outreach Education. 1995. (videocassette). Contact: Available from University of Wisconsin Hospital and Clinics. Picture of Health, 702 North Blackhawk Avenue, Suite 215, Madison, WI 53705-3357. (800) 757-4354 or (608) 263-6510. Fax (608) 262-7172. PRICE: $19.95 plus shipping and handling; bulk copies available. Order number 020195A. Summary: More than one million people will discover they have gallstones this year, and most will be women. Not all gallstones cause problems, but when they do, a variety of treatments are available. This videotape is one in a series of health promotion programs called 'Picture of Health,' produced by the University of Wisconsin. In this program, moderated by Mary Lee and featuring Dr. Eberhard Mack, the common symptoms, diagnosis, and management of gallstones are covered. Dr. Mack introduces the function of the gallbladder as a storage bag for bile, which is a 'detergent' produced

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by the liver that is used for digestion. Dr. Mack shows an illustration of the anatomy of the gastrointestinal tract, including the gallbladder, and describes where gallstones tend to form. Dr. Mack then shows actual gallstones, one a cholesterol stone, one a black pigment stone, and describes how gallstones form and the speed of growth of different types of stones. Risk factors for gallstones include being gender, being over 40, having a fair complexion (genetics), having a familial tendency, losing weight rapidly, and giving birth to many children. Symptoms include sudden onset of pain in the upper right quadrant of the abdomen, sometimes accompanied by nausea or vomiting. The pain is usually one to two hours in duration, as the gallstone passes. Some people have gallstones that are asymptomatic. Diagnostic considerations include patient history, abdominal film (xray), ultrasound, and cardiovascular testing (to rule out cardiovascular disease). Dr. Mack reviews the complications of gallstones, including gallstone pancreatitis, acute cholecystitis (infection of the gallbladder), hydrops, and jaundice. The program concludes by describing the use of open cholecystectomy, using a mini incision technique, and the use of laparoscopic cholecystectomy; Dr. Mack demonstrates the instruments used for the latter technique. The program concludes by referring viewers to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). •

Gastroenterology for the Primary Care Physician Source: Mount Laurel, NJ: CME Conference Video, Inc. 1994. (instructional package). Contact: Available from CME Conference Video, Inc. 2000 Crawford Place, Suite 100, Mount Laurel, NJ 08054. (800) 284-8433. Fax (800) 284-5964. PRICE: $450 plus $12.25 shipping and handling (as of 1995); group practice package available. Program No. 153. Summary: This continuing education course is designed to update internists, family practitioners, and other primary care physicians on new developments in gastroenterology. The format of the course focuses on case presentations emphasizing important and evolving concepts in gastroenterology. The emphasis is on practical diagnostic and therapeutic choices and the development of cost effective management algorithms. Topics include hepatitis C, non-cardiac chest pain, psychopharmacologic approaches to acid reduction, peptic ulcer disease, Helicobacter pylori, risk factors for NSAID injury, Clostridium difficile, travelers' diarrhea, constipation in the elderly, pancreatitis, endoscopic ultrasound, gastroesophageal reflux disease, Barrett's esophagus, liver disease, GI manifestations in AIDS, esophagitis, fecal incontinence, diagnostic testing, irritable bowel syndrome, inflammatory bowel disease, drug therapy, chronic diarrhea, gallstone disease, colon cancer, cirrhosis, and ascites. The program offers 11 hours of AMA-PRA Category 1 credit. (AA-M).

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Postgraduate Gastroenterology Program Source: Mt. Laurel, NJ: CME Conference Video, Inc. 1992. (videocassettes and syllabus). Contact: Available from P.O. Box 5077, Cherry Hill, NJ 08034-5077. (800) 284-8433. Fax (800) 284-5964. PRICE: $675. Group practice packages available. Summary: This continuing education video series is designed to enhance understanding of pathophysiology and patient management of gastrointestinal (GI) organ systems and GI disorders and to improve viewers' diagnostic and treatment abilities. Six sections cover gastroduodenal disorders; clinical applications of research; liver diseases; pancreatic and biliary tract diseases; inflammatory bowel syndrome (IBS); and esophageal disorders. Specific topics include helicobacter pylori and peptic ulcer disease; gastric emptying; gastroparesis; hormones and neuropeptides; interferon

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therapy of chronic liver disease; liver transplantation; hepatic encephalopathy; sclerosing cholangitis; chronic pancreatitis; endoscopic retrograde cholangiopancreatography (ECRP); colorectal polyps; surgical therapy for IBS; IBS and constipation; swallowing physiology; and Barrett's esophagus. The video includes interactive sessions between experts in the field of gastroenterology. (AA-M). •

Advanced Therapeutic Endoscopy XII Source: Mt. Laurel, NJ: CME Conference Video, Inc. 1993. (videocassettes and syllabus). Contact: Available from P.O. Box 5077, Cherry Hill, NJ 08034-5077. (800) 284-8433. Fax (800) 284-5964. PRICE: $625.00. Summary: This continuing education videotape is designed to help gastroenterologists sharpen their therapeutic endoscopy skills. Six main sections discuss the biliary tree, basic and advanced techniques; current topics in therapeutic endoscopy; the pancreas; the upper gastrointestinal (GI) tract; and the colon. Specific topics include manometry; the use of stents; management of the difficult bile duct stone; sphincterotomy; endoscopic ultrasonography; endoscopic retrograde cholangiopancreatography (ECRP); cholecystectomy; chronic pancreatitis; variceal bleeding; upper GI tumor; enteroscopy; difficult colonoscopy; polypectomy; and the bleeding angiodysplasia. The tape includes break-out sections featuring authorities in endoscopy.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “pancreatitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on pancreatitis: •

Non-Surgical Treatment of Pain in Chronic Pancreatitis Source: Timonium, MD: Milner-Fenwick, Inc. 199x. (audiocassette). Contact: Available from Milner-Fenwick, Inc. 2125 Greenspring Drive, Timonium, MD 21093-9989. (800) 638-8652 or (301) 252-1700. PRICE: $14.95. Order number CAS 15. Summary: This audiocassette includes four programs about the non-surgical treatment of the pain associated with chronic pancreatitis. Chaired by Dr. Eugene DiMagno, the topics are: mechanisms of pain (Dr. Howard Reber, Los Angeles, CA); enzymes and feedback regulation (Dr. Chung Owyang, Ann Arbor, MI); endoscopic treatment (Dr. Joseph Geene, Racine, WI); and unproven treatments (Dr. Peter Banks, Boston, MA). (AA-M).

Bibliography: Multimedia on Pancreatitis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in pancreatitis (or synonyms). Then,

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in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on pancreatitis: •

Acute pancreatitis [electronic resource] Source: AACN [and] Medi-Sim, Inc; Year: 1987; Format: Electronic resource; Edwardsville, KS: Medi-Sim, c1987

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Acute pancreatitis [motion picture]: a photographic supplement for clinics or conferences Source: produced and distributed by Davis & Geck, division of American Cyanamid Company; produced by Hilger Perry Jenkins; Year: 1956; Format: Motion picture; United States: Davis & Geck, [1956]

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Acute pancreatitis [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1983; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1983

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Approach to the patient with fulminant pancreatitis [sound recording]: recorded at DDW 1989, Washington, D.C. Year: 1989; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, c1989

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Cellular basis of acute pancreatitis [sound recording]: recorded at DDW 1990, San Antonio. Year: 1990; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, c1990

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Controversies in management of pancreatitis [sound recording]: recorded at DDW 1991 in New Orleans. Year: 1991; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, [1991]

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Diagnosis and management of acute pancreatitis [sound recording] Source: American College of Surgeons; Year: 1980; Format: Sound recording; [Chicago]: The College, [1980]

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Diagnosis and management of pancreatitis [sound recording] Source: American College of Surgeons; Year: 1976; Format: Sound recording; Chicago, Ill.: The College, c1976

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Diagnosis and management of recurrent acute pancreatitis [sound recording]: recorded at DDW 1991 in New Orleans. Year: 1991; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Society, [1991]

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Exocrine pancreas [slide]: pancreatitis Source: [produced by American Gastroenterological Association; author, Travis E. Solomon]; Year: 1984; Format: Slide; [Thorofare, N.J.]: The Association, c1984

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Non-surgical treatment of pain in chronic pancreatitis [sound recording]: recorded at DDW 1990, San Antonio. Year: 1990; Format: Sound recording; [Bethesda, Md.]: American Gasteroenterological Association, c1990

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Nursing process and the patient with acute pancreatitis [filmstrip] Source: Medical Electronic Educational Services in cooperation with Western Wisconsin Technical Institute; Year: 1975; Format: Filmstrip; La Crosse: The Institute, c1975

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Pancreatitis [slide] Source: Thomas W. Sheehy; Year: 9999; Format: Slide; [Garden Grove, Calif.]: Medcom, c1983-

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Pancreatitis [slide] Source: [authors, Peter A. Banks. et al.]; Year: 1990; Format: Slide; [Bethesda, Md.]: American Gastroenterological Association, c1990

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Pancreatitis [slide] Source: [presented by the Ohio Medical Education Network]; Year: 1988; Format: Slide; [Columbus, Ohio]: The Network, [1988]

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Pancreatitis [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1982; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1982

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Surgical management of Crohn's disease; Distal pancreatectomy for chronic pancreatitis [videorecording] Source: Medicom International Incorporated; produced by Gregory Luque Productions, Inc; Year: 1987; Format: Videorecording; [Sarasota, Fla.]: Medicom, c1987

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

News Services and Press Releases One of the simplest ways of tracking press releases on pancreatitis is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “pancreatitis” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to pancreatitis. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “pancreatitis” (or synonyms). The following was recently listed in this archive for pancreatitis: •

Fungal infections common in patients with severe acute pancreatitis Source: Reuters Medical News Date: July 22, 2003

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Cimetidine ineffective for acute pancreatitis Source: Reuters Industry Breifing Date: July 23, 2002

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Variety of drugs boost pancreatitis risk after ERCP Source: Reuters Medical News Date: April 03, 2002

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Obesity and glyburide use associated with the acute pancreatitis risk Source: Reuters Medical News Date: February 11, 2002

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CT unnecessary in work-up of many patients with acute pancreatitis Source: Reuters Medical News Date: August 20, 2001

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Smoking speeds up cancer in pancreatitis patients Source: Reuters Health eLine Date: July 11, 2001

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Distal resection is safe and effective for postobstructive chronic pancreatitis Source: Reuters Medical News Date: July 02, 2001

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Hydroxyurea increases risk of pancreatitis in HIV-infected patients Source: Reuters Medical News Date: April 19, 2001

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Islet autotransplantation shows benefit after resection for chronic pancreatitis Source: Reuters Medical News Date: April 04, 2001

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IL-10 reduces incidence of post-ERCP pancreatitis Source: Reuters Industry Breifing Date: February 21, 2001

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Biliary drainage reduces liver fibrosis in patients with chronic pancreatitis Source: Reuters Medical News Date: February 07, 2001

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Hydroxyurea may trigger pancreatitis when combined with didanosine Source: Reuters Medical News Date: January 17, 2001

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Pirenzepine a beneficial alternative to nasogastric suction for acute pancreatitis Source: Reuters Medical News Date: January 12, 2001

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Acute pancreatitis with hepatitis B exacerbation has poor prognosis Source: Reuters Medical News Date: November 27, 2000

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Intravenous contrast may be harmful for patients with acute pancreatitis Source: Reuters Medical News Date: November 16, 2000

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Distal pancreatectomy increases risk for diabetes in pancreatitis patients Source: Reuters Medical News Date: November 15, 2000

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Loxiglumide may benefit patients with acute attacks of chronic pancreatitis Source: Reuters Industry Breifing Date: November 10, 2000

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Blood glucose levels have prognostic value in acute pancreatitis Source: Reuters Medical News Date: November 10, 2000

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Early resection plus islet transplant advised for patients with chronic pancreatitis Source: Reuters Medical News Date: October 10, 2000

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Serum glucose level predicts severe complications of gallstone pancreatitis Source: Reuters Medical News Date: September 20, 2000

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Abbott alerts physicians of life-threatening pancreatitis cases linked to Depakote Source: Reuters Industry Breifing Date: August 01, 2000

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ERCP usually detects cause of "idiopathic" recurrent pancreatitis Source: Reuters Industry Breifing Date: July 27, 2000

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Pancreas divisum an important cause of recurrent pancreatitis in children Source: Reuters Medical News Date: June 20, 2000

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Trypsinogen activation peptide predicts pancreatitis severity 24 hours after symptom onset Source: Reuters Medical News Date: June 06, 2000

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Serum IL-10 and IL-11 concentrations reflect acute pancreatitis severity Source: Reuters Medical News Date: December 24, 1999

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Bristol-Myers Squibb extends warning on ddI-related pancreatitis Source: Reuters Medical News Date: November 23, 1999

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Chronic pancreatitis patients who smoke at high risk of pancreatic cancers Source: Reuters Medical News Date: May 14, 1999

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Hydrocortisone use does not prevent pancreatitis after cholangiopancreatography Source: Reuters Medical News Date: April 22, 1999

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AIDS does not increase severity of acute pancreatitis Source: Reuters Medical News Date: March 18, 1999

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Idiopathic chronic pancreatitis linked to CFTR gene mutations Source: Reuters Medical News Date: September 03, 1998

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Pancreatitis linked to cystic fibrosis Source: Reuters Health eLine Date: September 02, 1998

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Extracorporeal Membrane Oxygenation Efficacious For ARDS Linked To Acute Pancreatitis Source: Reuters Medical News Date: April 28, 1998

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Pancreatitis May Not Increase Risk For Pancreatic Cancer Source: Reuters Medical News Date: August 13, 1997

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Small Gallstones Linked To Pancreatitis, Watchful Waiting 'Unwarranted' Source: Reuters Medical News Date: August 11, 1997

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New Dipstick Test Effective For Acute Pancreatitis Screening In The ED Source: Reuters Medical News Date: June 19, 1997

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Hereditary Pancreatitis Patients At Increased Risk Of Pancreatic Cancer Source: Reuters Medical News Date: March 28, 1997

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Early Intervention For Nonobstructive Biliary Pancreatitis Not Beneficial Source: Reuters Medical News Date: January 23, 1997

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Genes Linked To Hereditary Pancreatitis, Familial Psoriasis Identified Source: Reuters Medical News Date: October 02, 1996

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Ansan Acquires Rights For Pancreatitis Drug From Boehringer Ingelheim Source: Reuters Medical News Date: June 05, 1996

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Urinary Test Strip May Help Diagnose Acute Pancreatitis Source: Reuters Medical News Date: March 20, 1996

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Early Use of Antibiotics In Cases of Suspected Necrotizing Pancreatitis May Reduce Mortality Rates Source: Reuters Medical News Date: September 08, 1995

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Octreotide Shows Promise In The Treatment Of Acute Pancreatitis Source: Reuters Medical News Date: August 14, 1995

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Pancreatitis Predisposes Some Individuals To Pancreatic Cancer Source: Reuters Medical News Date: July 18, 1995

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CT-Associated Risk in Pancreatitis Plus New Marker For Pancreatic Cancer Featured At Gastroenterology Meeting Source: Reuters Medical News Date: May 15, 1995

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “pancreatitis” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “pancreatitis” (or synonyms). If you know the name of a company that is relevant to pancreatitis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “pancreatitis” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly

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to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “pancreatitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on pancreatitis: •

Following Endoscopic Therapy. Pancreatitis Patients Report Pain Relief Source: Gastroenterology and Endoscopy News. 51(10): 1, 41. 2000. Contact: Available from McMahon Publishing Group. 545 West 45th Street, 8th Floor, New York, NY 10036. (212) 957-5300. Website: www.mcmahonmed.com. Summary: This news article reports on a retrospective study that has demonstrated that endoscopic therapy can have significant long term benefits on patients with chronic pancreatitis (inflammation of the pancreas), and that the technique offers similar success rates to those of surgery, while being minimally invasive for the patient. The study revealed that more than 60 percent of patients with chronic pancreatitis or unexplained abdominal pain resulting from pancreatic sphincter dysfunction reported a greater than 50 percent decrease in their pain 16 months after endoscopic therapy. Complications of endoscopic pancreatic sphincterotomy (EPS) included pancreatitis (9 percent of patients), bleeding (4 percent of patients), and early stent occlusion (blockage) in 9 percent of patients. There were no deaths related to the procedure and no patient developed severe acute pancreatitis. The study results need to be evaluated further in a prospective fashion. The article includes the comments of one expert who cautions that the role of endoscopic therapy in pancreatic disease has always been controversial, especially because pancreatitis is a 'dreaded complication' of endoscopic therapy to the pancreas.

•

Pancreatitis: Painful Attacks Should Not Be Ignored Source: Mayo Clinic Health Letter. 17(10): 4-5. October 1999. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This newsletter article from the Mayo Clinic reviews the problem of pancreatitis attacks, stressing that acute pancreatitis warrants immediate medical care to avoid complications that can be fatal. Acute pancreatitis attacks consist of a sudden pain in the upper abdomen that seems to go straight through to the back and that does not ease up. The author briefly reviews the physiology and functions of the pancreas, including production of the hormones insulin and glucagon, which help regulate metabolism; and production of pancreatic juices and enzymes that are delivered to the upper part of the small intestine (duodenum) to help digest fats, proteins, and carbohydrates. Inflammation of the pancreas disrupts these functions. Acute pancreatitis comes on suddenly when digestive juices from the pancreas escape the ducts leading to the small intestine and instead enter pancreas tissue itself, causing potentially severe damage. Acute pancreatitis is usually caused by either gallstones leaving the gallbladder and obstructing the pancreatic duct, or by excessive alcohol use. Most attacks of pancreatitis range from mild to moderate and may last only a couple of days. Treatment often involves a hospital stay and no food or drink by mouth (in order to rest the pancreas). By comparison, chronic pancreatitis (progressive inflammation and damage to the pancreas) is sometimes difficult to detect early. Most of the time it is caused by excessive alcohol use over many years. Treatment for chronic pancreatitis focuses on

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pain management and preventing attacks by avoiding alcohol, following a careful diet, and working closely with a health care provider. 1 figure.

Academic Periodicals covering Pancreatitis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to pancreatitis. In addition to these sources, you can search for articles covering pancreatitis that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for pancreatitis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with pancreatitis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to pancreatitis: Corticosteroids •

Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html

•

Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Decadron Respihaler; Pulmicort Respules; Pulmicort Turbuhaler; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html

•

Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html

•

Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P.; HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html

•

Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html

•

Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectosol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html

Didanosine •

Systemic - U.S. Brands: Videx http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202616.html

Fenofibrate •

Systemic - U.S. Brands: Tricor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203516.html

Insulin •

Systemic - U.S. Brands: Humulin 50/50; Humulin 70/30; Humulin 70/30 Pen; Humulin L; Humulin N; Humulin N Pen; Humulin R; Humulin R, Regular U500 (Concentrated); Humulin U; Lente; Lente Iletin II; Novolin 70/30; Novolin 70/30 PenFill; Novolin 70/30 Prefilled; Novolin L; Novoli http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203298.html

Mumps Virus Vaccine Live •

Systemic - U.S. Brands: Mumpsvax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202382.html

Zalcitabine •

Systemic - U.S. Brands: HIVID http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202652.html

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

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APPENDICES

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

12

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

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.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 citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

13 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). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM 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 “pancreatitis” (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 35770 302 891 187 1 37151

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 “pancreatitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

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.

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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 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: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Pancreatitis In the following section, we will discuss databases and references which relate to the Genome Project and pancreatitis. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 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. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “pancreatitis” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for pancreatitis: •

Pancreatitis, Hereditary Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?167800

•

Pancreatitis, Sclerosing Cholangitis, and Sicca Complex Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?260480

•

Pancreatitis-Associated Protein Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?167805

•

Tropical Calcific Pancreatitis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?608189 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “pancreatitis” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “pancreatitis” (or synonyms) into the search box, and

24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on pancreatitis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to pancreatitis. 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 pancreatitis. 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 “pancreatitis”:

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•

Guides on pancreatitis Pancreatitis http://www.nlm.nih.gov/medlineplus/tutorials/pancreatitisloader.html

•

Other guides Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Pancreatic Cancer http://www.nlm.nih.gov/medlineplus/pancreaticcancer.html Pancreatic Diseases http://www.nlm.nih.gov/medlineplus/pancreaticdiseases.html Preventing Disease and Staying Healthy http://www.nlm.nih.gov/medlineplus/preventingdiseaseandstayinghealthy.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on pancreatitis. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Pancreatitis Source: Bethesda, MD: American Gastroenterological Association. 199x. [4 p.]. Contact: American Gastroenterological Association (AGA). 7910 Woodmont Avenue, Seventh Floor, Bethesda, MD 20814. (800) 668-5237 or (301) 654-2055. Fax (301) 652-3890. Website: www.gastro.org. PRICE: Single copy free; bulk copies available. Summary: Pancreatitis is inflammation of the pancreas; it usually begins at an acute stage and in some cases may become chronic after a severe or recurrent attack. When the pancreas becomes inflamed, the digestive enzymes attack the tissue that produces them. This brochure from the American Gastroenterological Association (AGA) reviews the problem of pancreatitis. Topics include a description of acute and chronic pancreatitis, the symptoms of pancreatitis, how to know if medical assistance should be consulted for abdominal pain, and treatment options. With chronic pancreatitis, the pancreas may

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eventually stop producing the enzymes that are necessary for the body to digest and absorb nutrients. The symptoms of pancreatitis include a gradual or sudden severe pain in the center part of the upper abdomen that goes through to the back, nausea and vomiting, fever, jaundice (a yellowing of the skin), shock, weight loss, and symptoms of diabetes mellitus. Most cases of acute pancreatitis are mild and involve a short hospital stay to help heal the pancreas. Chronic pancreatitis is a much more persistent condition and occurs more often in men than in women. Treatment focuses on nutritional and metabolic needs and on relieving the pain of pancreatitis. Surgery may be required to remove contributing gallstones, to drain the pancreatic duct, or to remove part of the pancreas. Most people who have chronic pancreatitis have a good prognosis if they follow the required dietary changes and take their medications and required supplements. The brochure includes a diagram of the digestive tract, with organs labeled, and a glossary of related terms. 1 figure. •

Pancreatitis: Understanding This Painful Condition Source: San Bruno, CA: StayWell Company. 1998. [2 p.]. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $ 17.95 for 50 copies; plus shipping and handling; bulk copies available. Order number 9779. Summary: This brochure describes acute pancreatitis (irritated or inflamed pancreas), a condition most often caused by gallstones. Acute pancreatitis is very painful and emergency medical treatment is usually needed. Symptoms include severe pain in the upper abdomen (that goes through to the back), nausea and vomiting, abdominal swelling and tenderness, fever, rapid pulse, and shallow, fast breathing. Blood tests are used to determine whether the symptoms are due to acute pancreatitis; health history and physical exam can help confirm the diagnosis. Other tests used include ultrasound (to confirm gallstones), CT scan (computed tomography, used to show how much the pancreas is inflamed), and ERCP (endoscopic retrograde cholangiopancreatography, which examines the common bile duct for gallstones). The brochure briefly describes the treatment for acute pancreatitis, which can include resting the pancreas (nutrition and fluids are given through an intravenous line), medications for the pain, and dietary modifications (after leaving the hospital). The brochure emphasizes the importance of avoiding alcohol. One sidebar describes chronic pancreatitis, which is most often due to continued drinking of alcohol. Another section describes the anatomy and function of the pancreas. The brochure is illustrated with full color drawings. 6 figures.

•

Acute Pancreatitis Source: Wexford, PA: National Pancreas Foundation. 200x. [4 p.]. Contact: Available from National Pancreas Foundation. P.O. Box 935, Wexford, PA 15090-0935. (866) 726-2737. Website: www.pancreasfoundation.org. PRICE: Single copy free. Summary: This brochure provides basic information about acute pancreatitis, a sudden inflammation of the pancreas that is usually associated with severe upper abdominal pain. The most common cause of acute pancreatitis is gallstones. Other causes include alcohol abuse, hereditary conditions, trauma, medications, infections, electrolyte abnormalities, high lipid levels, and hormonal abnormalities. The brochure reviews these causes, then discusses the clinical signs of acute pancreatitis, diagnostic tests used to confirm the condition, and treatment options. Treatment for acute pancreatitis depends on the severity of the condition. Sometimes the patient needs hospitalization

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with administration of intravenous fluids to help restore blood volume. Antibiotics are often prescribed if infection occurs and pain medications are often used to provide relief. Surgery is sometimes needed when complications such as infection, cysts, or bleeding occur. Patients usually recover fully form acute pancreatitis and do not experience recurrence if the cause is removed. 1 figure. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “pancreatitis” (or synonyms). The following was recently posted: •

ACR Appropriateness Criteria™ for acute pancreatitis Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3257&nbr=2483&a mp;string=pancreatitis

•

American Gastroenterological Association medical position statement: treatment of pain in chronic pancreatitis Source: American Gastroenterological Association - Medical Specialty Society; 1998 April 9 (reviewed 2001); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3068&nbr=2294&a mp;string=pancreatitis

•

Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues Source: European Registry of Hereditary Pancreatic Diseases - Disease Specific Society; 2001; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3374&nbr=2600&a mp;string=pancreatitis

•

Operative treatment for chronic pancreatitis Source: Society for Surgery of the Alimentary Tract, Inc - Medical Specialty Society; 1996 (revised 2000); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2167&nbr=1393&a mp;string=pancreatitis

•

Treatment of acute pancreatitis Source: Society for Surgery of the Alimentary Tract, Inc - Medical Specialty Society; 1996 (revised 2000 Jan); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2166&nbr=1392&a mp;string=pancreatitis

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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: •

Pancreatitis Summary: Pancreatitis is an inflammation of the pancreas. The pancreas is a large gland behind the stomach and close to the duodenum. The duodenum is the upper part of the small intestine. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6867 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 pancreatitis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to pancreatitis. By consulting all of associations listed in

246 Pancreatitis

this chapter, you will have nearly exhausted all sources for patient associations concerned with pancreatitis. 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 pancreatitis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “pancreatitis” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “pancreatitis”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “pancreatitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “pancreatitis” (or a synonym) into the search box, and click “Submit Query.”

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249

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

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

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

26

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

27

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

254 Pancreatitis

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

255

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on pancreatitis: •

Basic Guidelines for Pancreatitis Pancreatitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001144.htm SLE Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000435.htm

•

Signs & Symptoms for Pancreatitis Abdominal distention Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003122.htm Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

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Bowel sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003137.htm Chills Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003091.htm Erythema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Jaundice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003243.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Skin, clammy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003216.htm Sweating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •

Diagnostics and Tests for Pancreatitis Abdominal X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003815.htm Abdominal X-rays Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003815.htm Alkaline phosphatase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm Aspartate aminotransferase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003472.htm Bilirubin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003479.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm

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Glucagon Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003716.htm Secretin stimulation test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003892.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Background Topics for Pancreatitis Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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PANCREATITIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [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] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acupuncture Analgesia: Analgesia produced by the insertion of acupuncture needles at certain points in the body. These activate the small myelinated nerve fibers in the muscle which transmit impulses to the spinal cord and then activate three centers - the spinal cord, midbrain and pituitary hypothalamus - to produce analgesia. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many

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immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH]

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Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [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]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [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] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein

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which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [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] Alkalinization: The process by which a substance becomes an alkali. An alkali is the opposite of an acid. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allium: A genus of liliaceous herbs containing onions (Allium cepa), garlic (Allium sativum), and others; many produce pungent, often bacteriostatic and physiologically active compounds and are used as food, condiment, and medicament, the latter in traditional medicine. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-helix: One of the secondary element of protein. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by

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organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] 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] Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but

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shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] 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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiodysplasia: Degenerative, acquired lesions consisting of distorted, dilated, thin-walled vessels lined by vascular endothelium. This pathological state is seen especially in the gastrointestinal tract and is frequently a cause of upper and lower gastrointestinal hemorrhage in the elderly. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or

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positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergics: Medicines that calm muscle spasms in the intestine. Examples are dicyclomine (dy-SY-kloh-meen) (Bentyl) and hyoscyamine (HY-oh-SY-uh-meen) (Levsin). [NIH]

Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-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

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reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA 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] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the

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arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthritis, Juvenile Rheumatoid: Rheumatoid arthritis of children occurring in three major subtypes defined by the symptoms present during the first six months following onset: systemic-onset (juvenile-onset Still's disease), polyarticular-onset, and pauciarticular-onset. Adult-onset cases of Still's disease are also known. Only one subtype of juvenile rheumatoid arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent. [NIH] Articular: Of or pertaining to a joint. [EU] Ascariasis: Infection by nematodes of the genus Ascaris. Ingestion of infective eggs causes diarrhea and pneumonitis. Its distribution is more prevalent in areas of poor sanitation and where human feces are used for fertilizer. [NIH] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrovirus: A genus of small, circular RNA viruses in the family Astroviridae. They cause gastroenteritis and are found in the stools of several vertebrates including humans. Transmission is by the fecal-oral route. There are at least seven human serotypes and the type species is human astrovirus 1. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH]

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Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] 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] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] B cells: White blood cells that develop from bone marrow and produce antibodies. Also called B lymphocytes. [NIH]

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Backcross: A cross between a hybrid and either one of its parents. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Translocation: The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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]

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Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bezoars: Concretions of swallowed hair, fruit or vegetable fibers, or similar substances found in the alimentary canal. [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 Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]

Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] 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] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of

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tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [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] Body Regions: Anatomical areas of the body. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and

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is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [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] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caerulein: A specific decapeptide obtained from the skin of Hila caerulea, an Australian

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amphibian. Caerulein is similar in action and composition to cholecystokinin. It stimulates gastric, biliary, and pancreatic secretion and certain smooth muscle. It is used in paralytic ileus and as diagnostic aid in pancreatic malfunction. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

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Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspases: A family of intracellular cysteine endopeptidases. They play a key role in inflammation and mammalian apoptosis. They are specific for aspartic acid at the P1 position. They are divided into two classes based on the lengths of their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Celiac Artery: The arterial trunk that arises from the abdominal aorta and after a short course divides into the left gastric, common hepatic and splenic arteries. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by

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gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Celiac Plexus: A complex network of nerve fibers including sympathetic and parasympathetic efferents and visceral afferents. The celiac plexus is the largest of the autonomic plexuses and is located in the abdomen surrounding the celiac and superior mesenteric arteries. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [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] Cellule: In biology, a unit from which living organisms and tissues are built. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and

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learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoembolization: A procedure in which the blood supply to the tumor is blocked surgically or mechanically, and anticancer drugs are administered directly into the tumor. This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [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] Cholangiography: Radiographic examination of the bile ducts. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH]

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Cholecystitis: Inflammation of the gallbladder. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Choledocholithiasis: Gallstones in the bile ducts. [NIH] Cholelithiasis: Presence or formation of gallstones. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Choleretic: A choleretic agent. [EU] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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 Walking: A technique with which an unknown region of a chromosome can be explored. It is generally used to isolate a locus of interest for which no probe is available but that is known to be linked to a gene which has been identified and cloned. A fragment containing a known gene is selected and used as a probe to identify other overlapping fragments which contain the same gene. The nucleotide sequences of these fragments can then be characterized. This process continues for the length of the chromosome. [NIH]

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Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chyme: A thick liquid made of partially digested food and stomach juices. This liquid is made in the stomach and moves into the small intestine for further digestion. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]

Cirrhosis: A type of chronic, progressive liver disease. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH]

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Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] 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] Colonic Neoplasms: Tumors or cancer of the colon. [NIH] Colonic Polyps: Pedunculated or sessile growths arising from the mucous membrane of the colon. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH]

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Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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

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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] Computer Systems: Systems composed of a computer or computers, peripheral equipment, such as disks, printers, and terminals, and telecommunications capabilities. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH]

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Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [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] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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 Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

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Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the

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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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [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 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] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the

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central or peripheral nervous system. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] 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] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [NIH] Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral

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DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. [NIH] Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to didanosine (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] 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] 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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is

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roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [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 Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duke: A lamp which produces ultraviolet radiations for certain ophthalmologic therapy. [NIH]

Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] 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

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in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH]

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Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [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] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emodin: Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Encopresis: Incontinence of feces not due to organic defect or illness. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said

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of a disease or agent. Called also endemial. [EU] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopic retrograde cholangiopancreatography: ERCP. A procedure to x-ray the pancreatic duct, hepatic duct, common bile duct, duodenal papilla, and gallbladder. In this procedure, a thin, lighted tube (endoscope) is passed through the mouth and down into the first part of the small intestine (duodenum). A smaller tube (catheter) is then inserted through the endoscope into the bile and pancreatic ducts. A dye is injected through the catheter into the ducts, and an x-ray is taken. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The

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enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [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] 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] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Enteroscopy: An examination of the small intestine with an endoscope. The endoscope is inserted through the mouth and stomach into the small intestine. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastralgia: Pain in the epigastrium. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic

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vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Motility Disorders: Disorders affecting the motor function of the upper or lower esophageal sphincters, the esophageal body, or a combination of these parts. The failure of the sphincters to maintain a tonic pressure may result in the impeding of the passage of food, regurgitation of food, or reflux of gastric acid into the esophagus. [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]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and

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distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethionine: 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms. [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] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far

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below usual levels for age. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibrositis: Aching, soreness or stiffness of muscles; often caused by inexpedient work postures. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer

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to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [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] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Foot Care: Taking special steps to avoid foot problems such as sores, cuts, bunions, and calluses. Good care includes daily examination of the feet, toes, and toenails and choosing shoes and socks or stockings that fit well. People with diabetes have to take special care of their feet because nerve damage and reduced blood flow sometimes mean they will have less feeling in their feet than normal. They may not notice cuts and other problems as soon as they should. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [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

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of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gabexate: A serine proteinase inhibitor used therapeutically in the treatment of pancreatitis, disseminated intravascular coagulation (DIC), and as a regional anticoagulant for hemodialysis. The drug inhibits the hydrolytic effects of thrombin, plasmin, and kallikrein, but not of chymotrypsin and aprotinin. [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] 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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also

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enterogastritis. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Hemorrhage: Bleeding in the gastrointestinal tract. [NIH] Gastrointestinal Hormones: Hormones secreted by the gastrointestinal mucosa that affect the timing or the quality of secretion of digestive enzymes, and regulate the motor activity of the digestive system organs. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [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 Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [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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Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] 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 cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [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] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH]

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Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alphadecarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining gaba levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15. [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]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycodeoxycholic Acid: A bile salt formed in the liver by conjugation of deoxycholate with glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and choleretic. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH]

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Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] 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] Group Practice: Any group of three or more full-time physicians organized in a legally recognized entity for the provision of health care services, sharing space, equipment, personnel and records for both patient care and business management, and who have a predetermined arrangement for the distribution of income. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH]

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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] Gynecologic cancer: Cancer of the female reproductive tract, including the cervix, endometrium, fallopian tubes, ovaries, uterus, and vagina. [NIH] Haematemesis: The vomiting of blood. [EU] Haematuria: Blood in the urine. [EU] Haemophilia: A haemorrhagic diathesis occurring in two main forms: 1. Haemophilia A (classic haemophilia, factor VIII deficiency), an X-linked disorder due to deficiency of coagulation factor VIII; 2. Haemophilia B (factor IX deficiency, Christmas disease), also Xlinked, due to deficiency of coagulation factor IX. Both forms are determined by a mutant gene near the telomere of the long arm of the X chromosome (Xq), but a different loci, and are characterized by subcutaneous and intramuscular haemorrhages; bleeding from the mouth, gums, lips, and tongue; haematuria; and haemarthroses. [EU] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Helicobacter pylori: A spiral bacterium active as a human gastric pathogen. It is a gramnegative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus Campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the microorganism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405). [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemobilia: Hemorrhage in or through the biliary tract, due to trauma, inflammation,

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cholelithiasis, vascular disease, or 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] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [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] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heparin-binding: Protein that stimulates the proliferation of endothelial cells. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [NIH] Hepatic Duct, Common: Predominantly extrahepatic bile duct which is formed by the junction of the right and left hepatic ducts, which are predominantly intrahepatic, and, in turn, joins the cystic duct to form the common bile duct. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic

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alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis, Chronic: A collective term for a clinical and pathological syndrome which has several causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. Specific forms of chronic hepatitis include autoimmune hepatitis, chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, indeterminate chronic viral hepatitis, cryptogenic chronic hepatitis, and drug-related chronic hepatitis. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hepatoma: A liver tumor. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] 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] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

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

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH]

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Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogenate: A suspension of animal tissue that is ground in the all-glass "homogenizer" described by Potter and Elvehjem in 1936. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]

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Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hyperstimulation: Excessive stimulation. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Renal: Hypertension due to renal diseases, especially chronic parenchymal disease. Hypertension as a result of compression or obstruction of the renal artery or its branches is hypertension, renovascular. [NIH] Hypertension, Renovascular: Hypertension due to compression or obstruction of the renal artery or its branches. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperthermic perfusion: A procedure in which a warmed solution containing anticancer drugs is used to bathe, or is passed through the blood vessels of, the tissue or organ containing the tumor. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

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Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Ileus: Obstruction of the intestines. [EU] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large

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amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Impaction: The trapping of an object in a body passage. Examples are stones in the bile duct or hardened stool in the colon. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltrating cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called invasive cancer. [NIH]

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Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Information Systems: Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information. [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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [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

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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-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestinal Obstruction: Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anus. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]

Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH]

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Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intraperitoneal chemotherapy: Treatment in which anticancer drugs are put directly into the abdominal cavity through a thin tube. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]

Invasive cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer. [NIH] Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal

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blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increases vascular permeability and affects smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein (EC 3.4.21.34), tissue kallikrein (EC 3.4.21.35), and prostate-specific antigen (EC 3.4.21.77). [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [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 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] Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [NIH]

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Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lanthanum: The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [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] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] 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] Leukemia: Cancer of blood-forming tissue. [NIH]

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Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] 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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH]

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Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [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 cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutetium: Lutetium. An element of the rare earth family of metals. It has the atomic symbol Lu, atomic number 71, and atomic weight 175. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH]

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Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [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] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [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] Macronutrients: Nutrients in the diet that are the key sources of energy, namely protein, fat, and carbohydrates. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet.

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[NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Manometry: Tests that measure muscle pressure and movements in the GI tract. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Assistance: Financing of medical care provided to public assistance recipients. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH]

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Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Micelles: Electrically charged colloidal particles or ions consisting of oriented molecules; aggregates of a number of molecules held loosely together by secondary bonds. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through

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this network. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU]

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Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [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] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multigene Family: The progeny of a single open-pollinated parent or of a single cross between two individuals. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones

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proteinuria, and anemia. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion.

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[NIH]

Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myositis: Inflammation of a voluntary muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] 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] 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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Hepatitis: Irritation of the liver with no known cause. Occurs in newborn babies. Symptoms include jaundice and liver cell changes. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH]

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Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurogenic Inflammation: Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

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Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] 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] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [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

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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] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Nonulcer Dyspepsia: Constant pain or discomfort in the upper GI tract. Symptoms include burning, nausea, and bloating, but no ulcer. Possibly caused by muscle spasms. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] 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] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [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] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Management: Planning, organizing, and administering activities in an office. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of

Dictionary 325

gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] 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] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH]

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Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH]

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Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pancreatectomy: Surgery to remove the pancreas. In a total pancreatectomy, a portion of the stomach, the duodenum, common bile duct, gallbladder, spleen, and nearby lymph nodes also are removed. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic enzymes: A group of proteins secreted by the pancreas which aid in the digestion of food. [NIH] Pancreatic Fistula: Abnormal passage communicating with the pancreas. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatic Pseudocyst: Cyst-like space not lined by epithelium and contained within the pancreas. [NIH] Pancreaticoduodenectomy: The excision of the head of the pancreas and the encircling loop of the duodenum to which it is connected. [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] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously,

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subcutaneously). [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [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. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH]

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Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perianal: Located around the anus. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perineural: Around a nerve or group of nerves. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneal Lavage: Washing out of the peritoneal cavity. The procedure is a diagnostic as well as a therapeutic technique following abdominal trauma or inflammation. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH]

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Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [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] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [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] Phosphorylates: Attached to a phosphate group. [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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [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] 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] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in

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sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plaque Assay: Method for measuring viral infectivity and multiplication in cultured cells. Clear lysed areas or plaques develop as the viral particles are released from the infected cells during incubation. With some viruses, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain viral antigens which can be measured by immunofluorescence. [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 Kallikrein: A peptidohydrolytic enzyme that is formed from prekallikrein by factor XIIA. It activates factor XII, factor VII, and plasminogen. It is selective for both arginine and to a lesser extent lysinebonds. EC 3.4.21.34. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [NIH] Platelet 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

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can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] 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] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymyalgia Rheumatica: A syndrome in the elderly characterized by proximal joint and muscle pain, high erythrocyte sedimentation rate, and a self-limiting course. Pain is usually accompanied by evidence of an inflammatory reaction. Women are affected twice as commonly as men and Caucasians more frequently than other groups. The condition is frequently associated with temporal arteritis and some theories pose the possibility that the two diseases arise from a single etiology or even that they are the same entity. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of

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cirrhosis. [NIH] Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Prekallikrein: A plasma protein which is the precursor of kallikrein. Plasma that is deficient in prekallikrein has been found to be abnormal in thromboplastin formation, kinin generation, evolution of a permeability globulin, and plasmin formation. The absence of prekallikrein in plasma leads to Fletcher factor deficiency, a congenital disease. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are

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not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [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] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Proctocolectomy: An operation to remove the colon and rectum. Also called coloproctectomy. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Proenzyme: 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] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or

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severity. [EU] Proinsulin: The substance made first in the pancreas that is then made into insulin. When insulin is purified from the pancreas of pork or beef, all the proinsulin is not fully removed. When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin is injected. The purified insulins have less proinsulin and other impurities than the other types of insulins. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Propanolamine: Ingredient used in cold and flue remedies. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH]

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Prostatic Neoplasms: Tumors or cancer of the prostate. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Proton Pump Inhibitors: Medicines that stop the stomach's acid pump. Examples are omeprazole (oh-MEH-prah-zol) (Prilosec) and lansoprazole (lan-SOH-prah-zol) (Prevacid). [NIH]

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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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudocysts: A collection of enzyme-rich pancreatic fluid and tissue debris arising within areas of necrosis or an obstructed smaller duct. [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] Public Assistance: Financial assistance to impoverished persons for the essentials of living through federal, state or local government programs. [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] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

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Pupil: The aperture in the iris through which light passes. [NIH] Purified Insulins: Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help avoid or reduce some of the problems of people with diabetes such as allergic reactions. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [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] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] 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] 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] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-

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immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH]

Radius: The lateral bone of the forearm. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] 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] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH]

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Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary,

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4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retroperitoneal Fibrosis: A slowly progressive condition of unknown etiology, characterized by deposition of fibrous tissue in the retroperitoneal space compressing the ureters, great vessels, bile duct, and other structures. When associated with abdominal aortic aneurysm, it may be called chronic periaortitis or inflammatory perianeurysmal fibrosis. [NIH]

Retroperitoneal Space: An area occupying the most posterior aspect of the abdominal cavity. It is bounded laterally by the borders of the quadratus lumborum muscles and extends from the diaphragm to the brim of the true pelvis, where it continues as the pelvic extraperitoneal space. [NIH]

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Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH]

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Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] 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] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [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] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to

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as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [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] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of

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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]

Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the

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extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasmolytic: Checking spasms; antispasmodic. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [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]

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Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenic Artery: The largest branch of the celiac trunk with distribution to the spleen, pancreas, stomach and greater omentum. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [NIH] Steatorrhea: A condition in which the body cannot absorb fat. Causes a buildup of fat in the stool and loose, greasy, and foul bowel movements. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other

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excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subcapsular: Situated below a capsule. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH]

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Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] 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] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [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

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meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Synovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. Synovitis is qualified as fibrinous, gonorrhoeal, hyperplastic, lipomatous, metritic, puerperal, rheumatic, scarlatinal, syphilitic, tuberculous, urethral, etc. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachykinins: A family of biologically active peptides sharing a common conserved Cterminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]

Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH]

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Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tendonitis: Inflammation of tendons attached to the biceps muscle, i. e. the main flexor muscle of the upper arm. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] 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]

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Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, 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] Thyroiditis: Inflammation of 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] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]

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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not

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undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Total pancreatectomy: Surgery to remove the entire pancreas. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] 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] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transcutaneous Electric Nerve Stimulation: Electrical stimulation of nerves and/or muscles to relieve pain; it is used less frequently to produce anesthesia. The optimal placements of electrodes or "trigger points" may correspond with acupuncture analgesia points. TENS is sometimes referred to as acupuncture-like when using a low frequency stimulus. [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] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH]

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Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [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] Triad: Trivalent. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tube-feeding: Feeding by a tube passed into the stomach. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

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Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [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]

Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH]

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Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urethritis: Inflammation of the urethra. [EU] Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] 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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [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] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure and flow rate, as well as oxygen content, are increased. [NIH]

Dictionary 357

Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Insufficiency: Inadequacy of the venous valves and impairment of venous return (venous stasis) usually from the legs, often with edema and sometimes with stasis ulcers at the ankle. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] 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] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Villous: Of a surface, covered with villi. [NIH]

358 Pancreatitis

Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] 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] Virus Diseases: A general term for diseases produced by viruses. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [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] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Whipple: An intestinal lipodystrophy; occurs in men and usually is associated with arthritis, diarrhea, and fat malabsorption. [NIH] Whipple procedure: A type of surgery used to treat pancreatic cancer. The head of the pancreas, the duodenum, a portion of the stomach, and other nearby tissues are removed. [NIH]

White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly

Dictionary 359

used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

361

INDEX A Aberrant, 78, 177, 178, 259 Abscess, 9, 19, 79, 141, 259 Acceptor, 259, 313, 326, 353 Acetaminophen, 135, 259, 296 Acetylcholine, 35, 259, 277, 323 Acidosis, 94, 259, 285, 311 Acne, 259, 310 Acne Vulgaris, 259, 310 Acquired Immunodeficiency Syndrome, 176, 259 Actin, 259, 322 Acupuncture Analgesia, 259, 353 Acute Disease, 165, 259 Acute lymphoblastic leukemia, 62, 259, 260 Acute lymphocytic leukemia, 260 Acute myelogenous leukemia, 191, 260 Acute myeloid leukemia, 260 Acute nonlymphocytic leukemia, 260 Adaptability, 260, 275 Adaptation, 71, 260 Adenine, 260, 338 Adenocarcinoma, 76, 86, 110, 115, 260, 303 Adenosine, 29, 42, 260, 311, 330 Adenovirus, 34, 36, 260 Adenylate Cyclase, 182, 260, 277, 295 Adipocytes, 260, 281, 312 Adipose Tissue, 260, 313, 351 Adjustment, 260 Adjuvant, 48, 260, 297 Adolescence, 15, 202, 260 Adrenal Cortex, 260, 283, 292, 304, 334 Adrenal Medulla, 261, 291, 324 Adrenergic, 76, 177, 261, 287, 291, 349 Adrenergic Agonists, 177, 261 Adverse Effect, 204, 261, 310, 345 Aerobic, 261, 306, 318, 326 Aerosol, 160, 261 Aetiology, 9, 112, 261 Afferent, 56, 70, 77, 261, 312 Affinity, 48, 51, 54, 66, 68, 72, 261, 267, 345 Affinity Chromatography, 54, 261 Agar, 261, 331 Agonist, 73, 76, 78, 133, 191, 261, 287, 323 Air Sacs, 261, 262 Albumin, 10, 261, 326, 331 Alcohol Dehydrogenase, 44, 63, 261

Aldehyde Dehydrogenase, 63, 262 Algorithms, 202, 212, 262, 271 Alimentary, 90, 103, 104, 108, 111, 116, 117, 244, 262, 270, 291, 327, 328 Alkaline, 161, 256, 259, 262, 263, 273, 330 Alkalinization, 170, 262 Alkaloid, 262, 273, 279, 319, 323 Alleles, 40, 262, 303 Allergen, 174, 195, 262, 344 Allium, 96, 262 Allogeneic, 69, 262 Allograft, 147, 262 Allopurinol, 141, 262 Allylamine, 262, 263 Alpha Particles, 262, 338 Alpha-1, 160, 262 Alpha-helix, 262, 311 Alternative medicine, 221, 262 Alveoli, 68, 262, 337, 357 Ameliorated, 50, 64, 138, 262 Ameliorating, 162, 170, 196, 262 Amine, 60, 262, 303 Amino Acid Sequence, 164, 179, 181, 189, 263, 265, 293, 298 Amino-terminal, 168, 263 Ammonia, 262, 263, 349, 355 Amphetamines, 263, 279 Amplification, 68, 263 Ampulla, 18, 263, 277, 290 Amylase, 7, 9, 12, 15, 17, 18, 23, 30, 41, 58, 59, 107, 158, 161, 183, 263 Amyloid, 92, 189, 263, 276 Anaerobic, 263, 306, 343 Anaesthesia, 118, 263, 307 Anal, 37, 130, 263, 294, 295 Analgesic, 259, 263, 317, 319, 325 Analog, 28, 263, 347 Analogous, 263, 287, 353 Anaphylatoxins, 263, 280 Anaphylaxis, 48, 264 Anastomosis, 5, 264 Anatomical, 57, 264, 271, 276, 289, 307, 318, 343 Androgens, 260, 264, 283 Anemia, 237, 264, 301, 320 Anesthesia, 264, 289, 334, 353 Anesthetics, 264, 269, 292 Aneurysm, 99, 264, 266

362 Pancreatitis

Angina, 161, 162, 192, 264 Angina Pectoris, 192, 264 Anginal, 264, 323 Angiodysplasia, 213, 264 Angiogenesis, 171, 264 Angioplasty, 186, 192, 264, 320 Angiotensin converting enzyme inhibitor, 50, 264 Animal model, 7, 34, 35, 45, 51, 52, 57, 62, 126, 264 Anionic, 54, 160, 264 Anions, 261, 264, 310, 344, 349 Ankle, 265, 356, 357 Anomalies, 20, 198, 202, 203, 265, 351 Anorexia, 263, 265, 296, 355 Anterior Cerebral Artery, 265, 276 Antibacterial, 265, 306, 346 Antibiotic, 13, 24, 42, 70, 84, 153, 168, 209, 265, 278, 292, 318, 321, 346 Antibiotic Prophylaxis, 24, 265 Antibody, 51, 66, 183, 188, 261, 265, 280, 292, 301, 304, 306, 307, 316, 319, 338, 344, 346 Anticholinergics, 18, 265 Anticoagulant, 265, 296, 336, 358 Anticonvulsant, 127, 265, 356 Antidiabetic, 265, 299 Antifungal, 5, 265 Antigen, 38, 48, 66, 88, 101, 261, 264, 265, 266, 280, 304, 305, 306, 307, 311, 316, 318, 338, 344 Antigen-Antibody Complex, 265, 280 Antihypertensive, 265, 295 Anti-inflammatory, 28, 32, 50, 68, 143, 171, 174, 195, 259, 265, 283, 298 Anti-Inflammatory Agents, 174, 195, 265, 283 Antimetabolite, 265, 293, 342 Antineoplastic, 266, 283, 305, 318, 326 Antioxidant, 59, 137, 266, 326 Antiserum, 179, 266 Antispasmodic, 266, 285, 325, 346 Antiviral, 64, 266, 309, 342 Antiviral Agents, 64, 266 Anuria, 266, 311 Anus, 263, 266, 268, 272, 279, 309, 329, 339 Aortic Aneurysm, 266, 341 Apolipoproteins, 64, 266, 297, 313 Apoptosis, 28, 30, 32, 44, 47, 59, 71, 77, 118, 122, 142, 191, 266, 274 Appendicitis, 4, 174, 185, 195, 201, 202, 266

Aqueous, 266, 269, 284, 289, 304, 312 Arachidonic Acid, 76, 171, 266, 313, 335 Arginine, 60, 194, 263, 266, 323, 331, 354 Aromatic, 72, 186, 266, 278, 330, 350 Arterial, 84, 95, 164, 262, 266, 267, 272, 274, 276, 277, 282, 305, 336, 350 Arteries, 266, 267, 271, 274, 275, 282, 283, 314, 317, 320, 352 Arteriolar, 55, 266, 267, 272 Arterioles, 266, 267, 271, 273, 317, 320 Arteriolosclerosis, 266, 267 Arteriosclerosis, 164, 187, 267, 276, 305 Arteriovenous, 91, 267, 276, 317 Arteritis, 267, 332 Artery, 64, 264, 265, 266, 267, 283, 289, 309, 320, 337, 340 Arthritis, Juvenile Rheumatoid, 193, 267 Articular, 267, 325 Ascariasis, 84, 96, 267 Asparaginase, 62, 89, 136, 139, 147, 267 Aspartate, 256, 267, 299 Aspartic, 179, 267, 274, 290 Aspartic Acid, 267, 274 Aspiration, 25, 267 Assay, 38, 42, 51, 74, 160, 183, 184, 194, 267, 306, 338, 355 Astrocytes, 48, 267, 302, 318 Astrovirus, 53, 267 Asymptomatic, 25, 57, 74, 212, 267, 327 Ataxia, 237, 268, 351 Atmospheric Pressure, 268, 305 Atopic, 190, 268 Atresia, 201, 268, 270, 282 Atrial, 268, 282, 358 Atrial Fibrillation, 268, 358 Atrophy, 40, 236, 237, 268, 313, 322 Attenuation, 68, 268 Atypical, 37, 41, 268 Autoantibodies, 81, 268 Autoantigens, 77, 268 Autodigestion, 168, 184, 185, 268, 327 Autoimmune disease, 19, 77, 177, 178, 187, 188, 191, 193, 268, 320 Autoimmune Hepatitis, 199, 268, 303 Autoimmunity, 47, 268 Autolysis, 54, 171, 268 Autonomic, 57, 259, 268, 275, 324, 329, 346, 349 Autonomic Nervous System, 57, 268, 329, 346, 349 Axons, 56, 268, 322, 325, 334

Index 363

B B cells, 57, 268, 284 Backcross, 46, 269 Bacteremia, 42, 196, 269, 343 Bacterial Infections, 4, 269 Bacterial Physiology, 260, 269 Bacterial Translocation, 128, 269 Bactericidal, 269, 293 Bacteriophage, 269, 331, 343, 353 Bacteriostatic, 262, 269, 292 Bacterium, 269, 281, 301 Barbiturates, 269, 338 Basal Ganglia, 268, 269, 272, 276 Basal Ganglia Diseases, 268, 269 Base, 68, 159, 260, 269, 284, 285, 295, 298, 311, 329, 330, 350, 351, 355 Base Sequence, 269, 295, 298 Basement Membrane, 269, 293 Basophil, 191, 270 Benign, 37, 70, 75, 198, 209, 267, 270, 298, 321 Beta-Lactamases, 270, 306 Beta-pleated, 263, 270 Bezoars, 202, 270 Bilateral, 116, 270, 328, 341 Bile Acids, 270, 297, 347, 350 Bile Acids and Salts, 270 Bile Pigments, 270, 310 Biliary, 4, 5, 6, 8, 10, 12, 13, 14, 15, 18, 20, 21, 22, 25, 31, 44, 49, 81, 82, 84, 85, 86, 89, 99, 103, 105, 107, 108, 109, 110, 112, 119, 154, 165, 197, 198, 201, 207, 212, 213, 218, 220, 270, 273, 277, 280, 285, 301, 327 Biliary Atresia, 198, 270 Biliary Tract, 5, 10, 107, 154, 165, 201, 212, 270, 273, 301, 327 Bilirubin, 200, 256, 261, 270, 296, 305 Bioassay, 30, 76, 270 Bioavailability, 190, 270 Biological response modifier, 270, 308 Biological therapy, 270, 300 Biomarkers, 107, 270 Biopsy, 5, 26, 36, 41, 270, 271, 329 Biopsy specimen, 5, 271 Biotechnology, 58, 79, 80, 206, 221, 233, 235, 236, 237, 238, 271 Bladder, 197, 271, 280, 307, 320, 322, 335, 355, 356 Bloating, 271, 297, 307, 315, 324 Blood Cell Count, 271, 301 Blood Coagulation, 194, 271, 273, 351

Blood Coagulation Factors, 271 Blood Glucose, 57, 271, 302, 305, 306, 308 Blood Platelets, 271, 344, 351 Blood pressure, 64, 169, 193, 265, 271, 274, 305, 306, 319, 323, 332, 346 Blood Volume, 165, 244, 271 Blood-Brain Barrier, 192, 271 Blot, 30, 33, 74, 96, 271 Body Composition, 27, 271 Body Fluids, 270, 271, 287, 295, 324, 346, 354 Body Regions, 271, 279 Bolus, 128, 271 Bolus infusion, 271 Bone Marrow, 260, 268, 271, 297, 306, 315, 319, 320, 333, 345, 346, 348 Bone Resorption, 191, 272 Bowel Movement, 272, 286, 347, 348 Bradykinin, 145, 192, 272, 310, 323, 331 Brain Infarction, 187, 188, 272 Brain Stem, 272, 275, 322 Brain Stem Infarctions, 272 Branch, 110, 253, 272, 288, 302, 315, 325, 328, 340, 346, 347, 351 Breakdown, 272, 285, 286, 296 Breeding, 163, 272 Bronchi, 163, 272, 292, 353 Bronchial, 272, 303 Bronchioles, 262, 272, 337 Bronchitis, 272, 278 Bronchoconstriction, 272, 331 Buccal, 272, 314 Burns, 42, 167, 196, 272 Burns, Electric, 272 Bursitis, 193, 272 Butyric Acid, 272, 293 C Cachexia, 161, 162, 176, 272 Caerulein, 28, 43, 46, 70, 142, 144, 145, 146, 272 Calcification, 10, 15, 64, 267, 273 Calcium, 19, 24, 57, 73, 80, 133, 158, 174, 195, 273, 280, 312, 317, 320, 323, 326, 336, 345 Calcium channel blocker, 133, 273 Calcium Oxalate, 273, 326 Calculi, 17, 131, 273, 300 Capillary, 68, 272, 273, 313, 333, 357 Capillary Permeability, 272, 273 Capsaicin, 70, 77, 273 Capsid, 80, 273, 358

364 Pancreatitis

Carbohydrate, 165, 185, 200, 203, 273, 283, 298, 299, 300, 332 Carbon Dioxide, 273, 284, 295, 296, 299, 340, 355, 357 Carboxy, 191, 273 Carcinogen, 59, 76, 273 Carcinogenesis, 45, 76, 202, 273 Carcinogenic, 273, 308, 335, 347 Carcinoma, 7, 20, 59, 74, 108, 109, 121, 180, 198, 273 Cardiomyopathy, 69, 274 Cardiorespiratory, 27, 274 Cardiovascular, 27, 65, 161, 162, 169, 181, 193, 200, 212, 274, 285, 313, 344, 346, 350 Cardiovascular disease, 27, 169, 193, 200, 212, 274, 313 Carrier Proteins, 169, 274, 331, 339 Case report, 26, 80, 83, 84, 85, 88, 101, 119, 124, 127, 136, 144, 145, 147, 274, 278 Caspases, 32, 274 Catabolism, 41, 64, 80, 274 Cataract, 162, 274 Catecholamines, 29, 261, 274, 287 Catheter, 79, 274, 289, 290 Catheterization, 264, 274, 320 Cathode, 274 Cations, 48, 274, 310 Caudal, 159, 274, 286, 306, 333 Causal, 171, 193, 274, 302 Cause of Death, 8, 42, 274 Caustic, 201, 202, 274 Celiac Artery, 274, 302 Celiac Disease, 148, 199, 200, 201, 202, 274 Celiac Plexus, 140, 275 Cell Adhesion, 34, 275 Cell Death, 19, 28, 30, 32, 63, 74, 266, 275 Cell Differentiation, 69, 126, 275, 345 Cell Division, 236, 269, 275, 300, 318, 331, 335, 343 Cell Lineage, 61, 70, 275 Cell membrane, 39, 171, 274, 275, 285, 293, 330, 346 Cell motility, 275, 303 Cell proliferation, 59, 71, 267, 275, 345 Cell Survival, 275, 300 Cellule, 275 Cellulose, 275, 331 Centrifugation, 275, 301, 318 Cerebellar, 268, 275, 339 Cerebellum, 272, 275, 339

Cerebral, 85, 162, 168, 181, 265, 268, 269, 271, 272, 275, 276, 282, 292, 293, 296, 321, 351 Cerebral Cortex, 268, 275, 293, 321 Cerebral hemispheres, 269, 272, 275, 276 Cerebral Hemorrhage, 181, 276 Cerebral Infarction, 181, 272, 276 Cerebrovascular, 269, 274, 276, 351 Cerebrum, 275, 276, 354 Cervical, 164, 276 Cervix, 276, 301 Character, 264, 276, 284, 299 Chemoembolization, 8, 276 Chemokines, 30, 52, 64, 73, 106, 276 Chemotactic Factors, 276, 280, 323 Chemotherapeutic agent, 66, 276 Chemotherapy, 136, 158, 159, 276 Chest Pain, 212, 276 Chin, 147, 276, 317 Cholangiography, 15, 276 Cholangitis, 8, 84, 85, 105, 108, 174, 184, 185, 195, 198, 213, 236, 276 Cholecystectomy, 15, 16, 50, 105, 201, 208, 212, 213, 276 Cholecystitis, 5, 107, 198, 201, 212, 277 Cholecystokinin, 7, 30, 32, 35, 43, 55, 68, 73, 127, 138, 273, 277 Choledocholithiasis, 16, 198, 277 Cholelithiasis, 5, 11, 15, 50, 173, 208, 277, 302 Cholera, 53, 77, 277, 344, 357 Cholera Toxin, 77, 277 Choleretic, 277, 299 Cholestasis, 200, 277 Cholesterol, 50, 64, 148, 169, 173, 187, 193, 212, 270, 277, 278, 283, 288, 296, 297, 305, 313, 314, 316, 343, 347 Cholesterol Esters, 277, 313 Choline, 50, 128, 277 Cholinergic, 277, 323 Chondrocytes, 191, 277, 294 Chorioretinitis, 277, 341 Choroid, 277, 341, 356 Chromatin, 266, 277 Chromosomal, 86, 154, 263, 277, 350 Chromosome, 40, 163, 166, 277, 281, 301, 313, 343, 350, 354 Chromosome Walking, 167, 277 Chronic Disease, 4, 29, 272, 278, 279, 312 Chronic Fatigue Syndrome, 38, 278 Chronic Obstructive Pulmonary Disease, 186, 187, 188, 278

Index 365

Chronic renal, 17, 278, 332, 355 Chylomicrons, 278, 313 Chyme, 185, 278 Chymotrypsin, 278, 296 Cilastatin, 278, 306 Cirrhosis, 5, 6, 29, 127, 198, 203, 212, 278, 302, 333, 334 Cisplatin, 159, 278 Clarithromycin, 82, 278 Clear cell carcinoma, 278, 285 Climacteric, 192, 278 Clinical Medicine, 146, 278, 333 Clinical study, 86, 278, 282 Clinical trial, 9, 11, 27, 30, 59, 65, 106, 124, 153, 155, 233, 278, 282, 287, 319, 328, 336, 339 Cloning, 45, 167, 271, 278 Coagulation, 65, 147, 176, 194, 271, 279, 296, 301, 302, 331, 352, 358 Coca, 279 Cocaine, 72, 279 Cod Liver Oil, 279, 289 Cofactor, 279, 336, 351 Colchicine, 139, 279 Colic, 4, 5, 279 Colitis, 208, 279 Collagen, 263, 269, 279, 294, 297, 304, 332 Collagen disease, 279, 304 Collapse, 45, 264, 272, 279 Colloidal, 261, 279, 288, 317, 329, 344 Colon, 36, 56, 140, 172, 200, 212, 213, 236, 279, 280, 307, 308, 312, 334, 345, 355 Colonic Neoplasms, 203, 279 Colonic Polyps, 200, 279 Colonoscopy, 36, 45, 213, 279 Colorectal, 44, 53, 199, 213, 280 Colorectal Cancer, 53, 199, 280 Combination chemotherapy, 144, 280 Combination Therapy, 169, 193, 280, 292 Combinatorial, 72, 280 Common Bile Duct, 5, 7, 13, 15, 16, 117, 119, 121, 184, 243, 280, 283, 302, 327 Complement, 188, 263, 280, 298, 331, 344 Complementary and alternative medicine, 135, 149, 280 Complementary medicine, 135, 280 Compliance, 108, 112, 280 Computational Biology, 233, 235, 280 Computed tomography, 4, 6, 7, 9, 10, 15, 18, 19, 22, 23, 25, 26, 84, 243, 281 Computer Systems, 38, 281 Computerized tomography, 64, 158, 281

Conception, 281, 294, 347 Concomitant, 95, 281 Concretion, 273, 281 Cone, 281, 330 Congestive heart failure, 186, 190, 281 Conjugated, 270, 281, 284 Conjugation, 281, 299 Conjunctiva, 281 Conjunctivitis, 168, 281 Connective Tissue, 164, 272, 279, 281, 294, 296, 297, 314, 317, 336, 342, 350, 351 Connective Tissue Cells, 281 Consciousness, 263, 281, 284, 287, 302, 341 Constipation, 200, 201, 202, 203, 212, 213, 282, 329 Constitutional, 282, 341 Constriction, 282, 310, 357 Consultation, 18, 282 Consumption, 4, 8, 29, 67, 142, 207, 282, 296, 324, 341 Contamination, 282, 303, 342 Continuous infusion, 30, 282 Contraindications, ii, 282 Control group, 13, 17, 27, 282 Controlled clinical trial, 6, 40, 48, 282 Convulsions, 265, 282, 288, 333 Coordination, 275, 282, 320 Cor, 282 Cornea, 282, 343, 356 Coronary, 64, 169, 186, 192, 264, 274, 282, 283, 317, 320 Coronary Arteriosclerosis, 282, 320 Coronary Circulation, 264, 282 Coronary heart disease, 169, 274, 283 Coronary Thrombosis, 283, 317, 320 Cortex, 283, 303, 326, 339 Corticosteroid, 88, 91, 283, 333 Cortisol, 261, 283 Cowpox, 283, 356 Cowpox Virus, 283, 356 Cranial, 159, 275, 283, 322, 325, 327, 329 Critical Care, 10, 22, 87, 107, 116, 122, 196, 204, 283 Crossing-over, 283, 339 Cultured cells, 283, 331 Curative, 62, 283, 351 Cutaneous, 283, 305, 314, 356 Cyanide, 20, 283 Cyclic, 68, 260, 283, 295, 301, 324, 335 Cyst, 13, 209, 283, 327 Cysteine Endopeptidases, 274, 283, 290 Cystic Duct, 280, 283, 302

366 Pancreatitis

Cytochrome, 33, 49, 283 Cytokine, 21, 29, 30, 45, 65, 69, 74, 126, 182, 186, 188, 284 Cytoplasm, 78, 266, 275, 277, 284, 291, 300, 322 Cytosine, 284, 338 Cytoskeleton, 53, 172, 284, 318 Cytotoxic, 176, 273, 284, 345 Cytotoxicity, 262, 278, 284 D Dairy Products, 284, 343 Data Collection, 284, 295 Deamination, 284, 286, 355 Decarboxylation, 284, 299, 303 Decompression, 5, 7, 21, 23, 284 Degenerative, 191, 264, 284, 302, 325 Dehydration, 88, 277, 284 Deletion, 43, 68, 266, 284 Dementia, 48, 69, 189, 259, 284, 322 Demyelinating Diseases, 162, 284 Dendrites, 285, 323 Density, 64, 167, 169, 175, 186, 275, 285, 288, 313, 325, 346 Depolarization, 285, 345 Dermatitis, 174, 181, 190, 195, 285 DES, 130, 167, 263, 285 Deuterium, 285, 304 Diabetes Mellitus, 12, 14, 20, 54, 64, 88, 95, 167, 178, 205, 208, 243, 285, 299, 302 Diabetic Ketoacidosis, 101, 285 Diabetic Retinopathy, 181, 285, 330 Diagnostic Errors, 42, 285 Diagnostic procedure, 37, 157, 221, 285 Dialyzer, 285, 302 Diarrhea, 200, 201, 202, 203, 212, 267, 285, 315, 358 Diarrhoea, 285, 296 Diastolic, 285, 305 Diathesis, 285, 301 Dicyclomine, 265, 285 Didanosine, 80, 94, 116, 218, 226, 285, 286 Dideoxyadenosine, 286 Diencephalon, 286, 306, 322, 351 Dietary Fats, 286, 313 Dietitian, 27, 286 Digestive system, 41, 156, 199, 201, 203, 286, 297 Digestive tract, 161, 200, 201, 243, 286, 345 Dihydrotestosterone, 286, 340 Dilatation, 264, 286, 309, 334, 337 Dilation, 93, 272, 286 Diploid, 286, 331

Direct, iii, 49, 61, 75, 79, 90, 159, 163, 199, 225, 278, 286, 287, 327, 340, 349 Discrete, 184, 286, 351 Disease Progression, 12, 18, 286 Disinfectant, 286, 293 Disposition, 44, 286 Dissection, 11, 91, 286 Dissociation, 261, 286 Distal, 13, 21, 107, 215, 218, 287, 297, 334, 337 Distention, 255, 287 Dopamine, 279, 287, 323, 330 Dorsal, 56, 70, 287, 333 Dose-dependent, 62, 287 Dosimetry, 66, 287 Double-blind, 112, 130, 135, 287 Drug Design, 67, 287 Drug Interactions, 204, 208, 227, 287 Drug Tolerance, 287, 352 Duke, 69, 131, 287 Duodenal Ulcer, 4, 13, 287 Dura mater, 287, 317, 326 Dyes, 263, 287 Dyslipidemia, 169, 193, 288 Dyspareunia, 288, 292 Dyspepsia, 199, 288, 307 Dysphagia, 203, 288 Dysplasia, 45, 190, 237, 288 Dyspnea, 288, 337 Dystrophy, 162, 236, 288 E Eating Disorders, 56, 202, 288 Eclampsia, 288, 333 Edema, 55, 65, 141, 285, 288, 320, 333, 355, 357 Effector, 32, 259, 280, 288, 322 Efficacy, 6, 10, 11, 40, 54, 59, 62, 63, 65, 77, 79, 146, 154, 207, 287, 288, 306 Effusion, 288, 350 Elastic, 288, 299, 346, 349 Elasticity, 164, 267, 282, 288 Elastin, 164, 279, 288 Elective, 5, 12, 16, 196, 288 Electrocoagulation, 279, 288 Electrolysis, 265, 274, 288 Electrolyte, 71, 200, 243, 283, 288, 295, 302, 311, 318, 324, 346, 355 Electrophoresis, 160, 288 Electrophysiological, 57, 288 Emaciation, 259, 288 Emboli, 289, 358 Embolism, 85, 289, 337, 358

Index 367

Embolization, 289, 358 Embolus, 289, 307 Embryo, 275, 289, 307 Embryology, 200, 289 Emesis, 204, 289 Emodin, 143, 289 Emphysema, 278, 289 Empiric, 72, 289 Emulsion, 208, 289, 295 Enamel, 289, 311 Encephalitis, 174, 195, 289 Encephalitis, Viral, 289 Encephalopathy, 124, 198, 289 Encopresis, 202, 289 Endarterectomy, 264, 289 Endemic, 277, 289, 347 Endocytosis, 170, 290 Endogenous, 55, 70, 72, 126, 268, 271, 287, 290, 299, 336, 353 Endometrial, 290 Endometriosis, 186, 290 Endometrium, 290, 301 Endopeptidases, 283, 290, 328, 336 Endorphins, 290, 323 Endoscope, 290, 291 Endoscopic, 4, 5, 7, 11, 13, 15, 16, 17, 18, 20, 21, 23, 25, 26, 41, 62, 89, 92, 93, 95, 97, 115, 117, 122, 123, 128, 183, 184, 201, 209, 212, 213, 222, 243, 279, 290, 345 Endoscopic retrograde cholangiopancreatography, 5, 7, 13, 15, 18, 20, 62, 89, 95, 97, 184, 201, 213, 243, 290 Endothelial cell, 290 Endothelium, 264, 290, 323 Endothelium-derived, 290, 323 Endotoxic, 290, 313 Endotoxin, 42, 47, 48, 65, 103, 290, 354 End-stage renal, 278, 290, 332 Energy balance, 290, 312 Enkephalins, 290, 323 Enteral Nutrition, 9, 16, 106, 132, 142, 143, 151, 203, 291 Enteritis, 174, 195, 291 Enterocolitis, 291 Enteropeptidase, 291, 354 Enteroscopy, 213, 291 Environmental Exposure, 291, 325 Environmental Health, 232, 234, 291 Enzymatic, 33, 184, 263, 273, 280, 286, 291, 294, 303, 316, 341

Enzyme, 4, 10, 14, 23, 26, 28, 31, 35, 40, 46, 49, 55, 56, 57, 59, 64, 74, 78, 152, 164, 165, 166, 180, 183, 184, 185, 189, 191, 260, 261, 262, 263, 267, 287, 288, 291, 294, 297, 299, 301, 310, 313, 314, 317, 320, 328, 331, 332, 334, 336, 337, 340, 342, 345, 348, 349, 351, 353, 355, 358, 359 Eosinophil, 191, 291 Eosinophilic, 93, 291 Epidemic, 291, 347 Epidermal, 171, 172, 174, 180, 195, 291, 316 Epidermal Growth Factor, 171, 172, 180, 291 Epidermal growth factor receptor, 171, 172, 291 Epidermis, 291, 311, 338 Epigastralgia, 8, 291 Epigastric, 166, 291, 326 Epinephrine, 60, 261, 287, 291, 323, 324, 355 Epithelial, 34, 56, 61, 70, 71, 77, 106, 174, 195, 260, 277, 291, 292, 303 Epithelial Cells, 34, 61, 71, 77, 277, 291, 292, 303 Epithelium, 56, 59, 70, 269, 290, 292, 296, 327 Epitope, 51, 66, 292 Erythema, 256, 292, 349, 356 Erythrocyte Volume, 271, 292 Erythrocytes, 264, 271, 272, 292, 302, 344 Erythromycin, 278, 292, 342 Escalation, 66, 292 Esophageal, 53, 201, 212, 292 Esophageal Motility Disorders, 201, 292 Esophagitis, 168, 200, 203, 212, 292 Esophagus, 53, 202, 203, 212, 213, 268, 286, 292, 297, 301, 314, 329, 340, 348 Essential Tremor, 237, 292 Estradiol, 292 Estramustine, 101, 292 Estrogen, 4, 146, 292 Estrogen Replacement Therapy, 146, 292 Ethanol, 30, 34, 43, 44, 46, 50, 63, 67, 76, 95, 165, 202, 261, 292, 294 Ether, 169, 193, 293 Ethionine, 50, 128, 146, 293 Ethnic Groups, 166, 293 Eukaryotic Cells, 293, 325, 355 Evacuation, 159, 282, 293, 296, 312 Evoke, 293, 347 Excitation, 263, 293, 323 Excitatory, 293, 299

368 Pancreatitis

Excrete, 266, 293, 311 Exocytosis, 39, 75, 170, 293 Exogenous, 20, 32, 55, 290, 293, 297, 299, 336 Exon, 75, 166, 293 Extensor, 293, 337 Extracellular, 29, 34, 43, 172, 180, 263, 267, 281, 290, 293, 294, 346 Extracellular Matrix, 180, 281, 293, 294 Extracellular Space, 293 Extravasation, 55, 293, 301 Exudate, 145, 277, 293, 325 Eye Infections, 260, 293 F Failure to Thrive, 201, 202, 293 Fallopian tube, 294, 301 Family Planning, 233, 294 Fatigue, 278, 294, 301 Fatty acids, 43, 64, 76, 130, 173, 261, 285, 294, 299, 314, 335, 351 Fecal Incontinence, 203, 212, 294, 307 Feces, 14, 267, 282, 289, 294, 348 Fermentation, 261, 294, 343 Fetus, 170, 294, 356 Fibrin, 65, 271, 294, 329, 331, 351, 352 Fibrinogen, 294, 331, 351 Fibrinolysis, 194, 294 Fibroblast Growth Factor, 180, 294 Fibroblasts, 180, 281, 294, 309 Fibrositis, 193, 294 Fistula, 163, 294, 296 Fixation, 294, 344 Flatus, 294, 295, 296 Flexor, 293, 295, 351 Fluid Therapy, 295, 324 Fluorescence, 38, 53, 194, 295 Focus Groups, 30, 295 Fold, 13, 43, 44, 295, 317, 324 Follow-Up Studies, 67, 295 Foot Care, 200, 295 Foramen, 276, 295, 329 Forearm, 271, 295, 339 Forskolin, 182, 295 Frameshift, 40, 295, 355 Frameshift Mutation, 295, 355 Free Radicals, 7, 19, 47, 118, 266, 286, 295, 320 Frontal Lobe, 265, 276, 296 Fulminant Hepatic Failure, 199, 201, 203, 296 Fungi, 265, 281, 293, 296, 317, 318, 359

G GABA, 296, 299, 345, 356 Gabexate, 87, 96, 118, 129, 296 Gadolinium, 48, 296 Gallstones, 3, 4, 7, 11, 20, 26, 97, 200, 201, 203, 208, 211, 220, 222, 243, 270, 277, 296 Ganglia, 259, 269, 296, 322, 329, 349 Gangrene, 163, 296 Gas, 200, 263, 273, 295, 296, 304, 307, 315, 323, 324, 337, 341, 348, 357 Gas exchange, 296, 341, 357 Gastric, 4, 97, 161, 173, 202, 212, 268, 273, 274, 291, 292, 296, 297, 301, 303, 324, 328 Gastric Emptying, 212, 296, 297 Gastric Juices, 296, 328 Gastric Mucosa, 296, 328 Gastrin, 296, 304 Gastritis, 29, 53, 170, 174, 195, 200, 201, 296, 301 Gastroduodenal, 212, 296 Gastroenteritis, 93, 267, 296, 342, 343 Gastroenterologist, 198, 297 Gastroesophageal Reflux, 199, 201, 204, 212, 297 Gastrointestinal Hemorrhage, 176, 199, 202, 264, 297 Gastrointestinal Hormones, 71, 297 Gastroparesis, 212, 297 Gastrostomy, 291, 297 Gelatin, 297, 299, 351 Gemcitabine, 66, 297 Gemfibrozil, 64, 297 Gene Expression, 33, 52, 57, 58, 61, 64, 71, 129, 140, 237, 297 Gene Targeting, 34, 297 Gene Therapy, 33, 47, 260, 297 Genetic Code, 298, 324 Genetic Engineering, 158, 271, 278, 298 Genetic testing, 11, 52, 244, 298 Genetics, 97, 100, 110, 113, 127, 167, 168, 212, 281, 298 Genital, 278, 298, 342 Genitourinary, 298, 350 Genomics, 50, 298 Genotype, 39, 41, 64, 90, 98, 298, 330 Germ cell tumors, 136, 298 Germ Cells, 298, 325, 326 Germline mutation, 63, 98, 298, 303 Gestational, 98, 178, 298 Gingivitis, 168, 174, 195, 298 Glomerular, 298, 311, 340 Glomeruli, 298

Index 369

Glomerulonephritis, 181, 298 Glomerulus, 298, 321 Glucocorticoid, 298, 304, 333 Gluconeogenesis, 298 Glucose Intolerance, 20, 285, 299 Glucose tolerance, 299 Glucose Tolerance Test, 299 Glucuronic Acid, 299, 302 Glucuronosyltransferase, 121, 299 Glutamate, 57, 77, 299 Glutamate Decarboxylase, 77, 299 Glutamic Acid, 179, 299, 323 Gluten, 199, 200, 275, 299 Glyburide, 113, 218, 299 Glycerol, 272, 299, 330 Glycerophospholipids, 299, 330 Glycine, 263, 270, 299, 323, 344 Glycodeoxycholic Acid, 49, 299 Glycogen, 31, 299 Glycoprotein, 34, 75, 188, 294, 300, 351, 354 Glycosaminoglycans, 300, 336 Glycoside, 300, 304, 343 Glycosylation, 179, 300 Gonadal, 300, 347 Gout, 181, 193, 279, 300 Governing Board, 300, 333 Grade, 5, 6, 194, 300 Grading, 5, 23, 25, 199, 300 Graft, 300, 304, 320 Gram-negative, 42, 47, 269, 290, 300, 301, 306, 343, 357 Gram-positive, 300, 306, 312 Granule, 35, 39, 75, 78, 300 Granulocytes, 32, 270, 300, 312, 345, 358 Group Practice, 212, 300 Growth factors, 66, 180, 300, 318 Guanylate Cyclase, 301, 324 Gynecologic cancer, 159, 301 H Haematemesis, 289, 301 Haematuria, 301 Haemophilia, 81, 301 Haploid, 301, 331 Haptens, 261, 301, 339 Health Promotion, 211, 301 Heart attack, 274, 301 Heart failure, 181, 192, 301, 337 Heartbeat, 301, 348 Heartburn, 201, 301, 307 Helicobacter, 13, 50, 80, 199, 212, 301 Helicobacter pylori, 13, 50, 199, 212, 301

Helix-loop-helix, 61, 301 Hematocrit, 117, 122, 271, 301 Hematoma, 91, 104, 301 Heme, 270, 284, 301 Hemobilia, 8, 198, 301 Hemochromatosis, 199, 201, 302 Hemodialysis, 9, 285, 296, 302, 311, 355 Hemofiltration, 86, 87, 302, 355 Hemoglobin, 60, 264, 271, 292, 301, 302, 312 Hemoglobinopathies, 297, 302 Hemoglobinuria, 236, 302 Hemolysis, 100, 302 Hemorrhage, 68, 104, 144, 176, 184, 198, 288, 301, 302, 320, 338, 348, 358 Hemostasis, 65, 194, 302, 344, 352 Heparan Sulfate Proteoglycan, 180, 302 Heparin, 101, 130, 180, 302 Heparin-binding, 180, 302 Hepatic Artery, 8, 302 Hepatic Duct, Common, 290, 302 Hepatic Encephalopathy, 199, 201, 213, 302 Hepatitis, 29, 35, 53, 105, 119, 174, 181, 187, 188, 192, 195, 198, 199, 201, 202, 203, 212, 218, 296, 302, 303, 358 Hepatitis A, 188, 303 Hepatitis, Chronic, 198, 303 Hepatocellular, 7, 8, 44, 49, 198, 199, 303 Hepatocellular carcinoma, 8, 44, 49, 198, 199, 303 Hepatocyte, 33, 176, 277, 303 Hepatocyte Growth Factor, 33, 303 Hepatology, 10, 12, 19, 25, 82, 91, 97, 103, 127, 132, 142, 198, 199, 209, 303 Hepatoma, 8, 303 Hepatorenal Syndrome, 176, 199, 303 Hepatovirus, 303 Hereditary mutation, 298, 303 Heredity, 203, 259, 297, 298, 303 Hernia, 202, 303 Heterodimer, 61, 303 Heterogeneity, 46, 58, 261, 303 Heterozygotes, 41, 303 Hippocampus, 303, 322 Histamine, 18, 50, 174, 195, 263, 303, 304 Histidine, 179, 303, 304 Histology, 15, 38, 65, 69, 200, 304, 322 Homeobox, 70, 304 Homeostasis, 35, 46, 61, 71, 182, 203, 304, 346 Homodimer, 61, 304

370 Pancreatitis

Homogenate, 64, 304 Homologous, 55, 262, 283, 297, 303, 304, 343, 344, 349, 354 Homotypic, 34, 304 Hormonal, 243, 268, 283, 292, 304 Host, 33, 38, 45, 53, 69, 164, 168, 174, 188, 195, 269, 304, 306, 313, 356, 358 Hybrid, 269, 304 Hybridomas, 162, 304, 309 Hydration, 4, 7, 9, 185, 304 Hydrocortisone, 113, 130, 219, 304 Hydrogen, 187, 191, 259, 261, 262, 269, 273, 285, 286, 304, 313, 319, 323, 326, 337, 349 Hydrogen Peroxide, 304, 313, 349 Hydrolases, 39, 304, 330 Hydrolysis, 173, 267, 270, 278, 304, 311, 313, 328, 330, 336, 354 Hydrophobic, 173, 299, 304, 313 Hydroxyproline, 263, 279, 305 Hydroxyurea, 80, 218, 305 Hyperalgesia, 77, 305 Hyperbaric, 141, 146, 305 Hyperbaric oxygen, 141, 146, 305 Hyperbilirubinemia, 305, 310 Hypercholesterolemia, 148, 175, 288, 305 Hyperglycemia, 77, 89, 305 Hyperlipidemia, 65, 126, 169, 175, 186, 187, 193, 288, 305 Hyperplasia, 49, 71, 305 Hypersensitivity, 262, 264, 291, 305, 313, 342, 344 Hyperstimulation, 43, 52, 68, 73, 305 Hypertension, 18, 54, 161, 162, 169, 192, 193, 198, 200, 267, 274, 276, 282, 305, 332, 333, 355 Hypertension, Renal, 169, 193, 305 Hypertension, Renovascular, 305 Hyperthermia, 46, 159, 305 Hyperthermic perfusion, 159, 305 Hypertriglyceridemia, 64, 88, 89, 101, 107, 143, 146, 175, 288, 305 Hypertrophy, 282, 305 Hyperuricemia, 300, 305 Hypesthesia, 305, 322 Hypoglycemic, 6, 60, 169, 193, 305, 306 Hypoglycemic Agents, 169, 193, 306 Hypotension, 15, 282, 306, 323, 331 Hypotensive, 306, 310 Hypothalamus, 259, 268, 286, 306, 323, 330, 346, 351 Hypoxia, 19, 46, 306, 351

I Id, 134, 148, 244, 245, 252, 254, 306 Ileum, 306, 323 Ileus, 192, 273, 306 Imipenem, 24, 278, 306 Immersion, 46, 306 Immune function, 71, 103, 306 Immune response, 29, 47, 65, 260, 265, 268, 283, 301, 306, 307, 344, 348, 354, 356, 358 Immune Sera, 306 Immune system, 178, 200, 268, 270, 306, 307, 313, 315, 320, 321, 356, 358 Immunity, 53, 78, 259, 306, 353 Immunization, 78, 306, 344 Immunoassay, 160, 306 Immunodeficiency, 236, 259, 306 Immunofluorescence, 306, 331 Immunogenic, 306, 313, 339 Immunoglobulin, 265, 306, 319 Immunologic, 26, 276, 306, 315 Immunology, 33, 65, 127, 191, 260, 261, 307 Immunosuppressive, 28, 50, 60, 298, 307, 350 Immunosuppressive therapy, 60, 307 Impaction, 18, 307 Impairment, 11, 20, 21, 48, 161, 268, 277, 293, 307, 309, 317, 357 Impotence, 169, 193, 307 In situ, 80, 307 In vitro, 28, 29, 32, 35, 43, 47, 51, 52, 54, 74, 77, 138, 141, 162, 180, 297, 307, 347, 350, 352 Incision, 79, 90, 154, 159, 212, 307, 310, 312 Incompetence, 297, 307 Incontinence, 177, 201, 285, 289, 307 Incubated, 28, 63, 194, 307 Incubation, 194, 307, 331 Indicative, 162, 166, 204, 307, 328, 357 Indigestion, 199, 307 Induction, 46, 49, 68, 69, 76, 127, 129, 142, 158, 176, 182, 188, 264, 307, 338 Infarction, 4, 65, 161, 162, 168, 185, 187, 188, 192, 276, 307, 340 Infertility, 37, 41, 168, 170, 192, 307, 311 Infiltrating cancer, 307, 310 Infiltration, 10, 45, 47, 55, 57, 68, 71, 88, 102, 298, 308, 334 Inflammatory bowel disease, 53, 144, 174, 177, 178, 181, 190, 193, 195, 200, 201, 203, 204, 208, 212, 308 Information Systems, 36, 308

Index 371

Informed Consent, 37, 308 Infusion, 28, 30, 35, 41, 50, 60, 64, 77, 84, 308, 320 Ingestion, 9, 144, 201, 202, 267, 299, 308, 332 Inhalation, 186, 226, 261, 308, 332 Initiation, 31, 42, 43, 47, 55, 178, 308, 353 Inlay, 308, 341 Inorganic, 278, 308, 319 Inositol, 68, 308 Insight, 26, 39, 52, 70, 77, 308 Insulator, 308, 320 Insulin-dependent diabetes mellitus, 38, 308 Insulin-like, 71, 308 Intensive Care, 5, 9, 13, 18, 28, 45, 107, 132, 176, 308 Intensive Care Units, 28, 308 Interferon, 29, 80, 191, 212, 308, 309, 315 Interferon-alpha, 309 Interleukin-1, 165, 183, 184, 186, 191, 309 Interleukin-10, 183, 184, 309 Interleukin-2, 309 Interleukin-6, 126, 309 Intermediate Filaments, 309, 322 Intermittent, 8, 167, 295, 309, 329 Internal Medicine, 40, 42, 43, 51, 76, 81, 126, 129, 130, 131, 136, 142, 297, 309 Interstitial, 25, 68, 206, 293, 309, 321, 340 Intestinal, 4, 40, 55, 71, 77, 97, 104, 136, 153, 161, 173, 177, 200, 202, 203, 208, 269, 274, 277, 291, 299, 301, 309, 312, 315, 358 Intestinal Mucosa, 71, 269, 275, 277, 291, 309 Intestinal Obstruction, 4, 203, 309 Intestine, 4, 35, 53, 59, 61, 75, 160, 185, 190, 200, 202, 222, 245, 265, 270, 272, 278, 280, 283, 287, 290, 291, 304, 306, 309, 312, 321, 338, 345, 354 Intoxication, 82, 309, 359 Intracellular Membranes, 309, 316 Intracranial Aneurysm, 276, 309 Intraepithelial, 74, 309 Intrahepatic, 8, 104, 302, 309 Intramuscular, 301, 309, 327 Intraocular, 295, 309 Intraocular pressure, 295, 309 Intraperitoneal, 130, 159, 310 Intraperitoneal chemotherapy, 159, 310 Intravascular, 14, 21, 147, 176, 194, 296, 310

Intravenous, 4, 9, 16, 40, 42, 62, 65, 144, 203, 218, 243, 244, 308, 310, 327 Intrinsic, 57, 261, 269, 310 Invasive, 45, 74, 79, 222, 306, 307, 310, 315 Invasive cancer, 74, 307, 310 Invertebrates, 165, 189, 310 Involuntary, 269, 292, 294, 310, 321, 344 Ion Channels, 267, 310, 350 Ion Exchange, 160, 275, 310 Ions, 48, 269, 286, 288, 304, 310, 317, 336, 346 Irrigation, 159, 310 Ischemia, 4, 11, 15, 19, 43, 49, 52, 65, 71, 112, 181, 187, 188, 268, 310, 320, 340 Islet, 33, 60, 62, 76, 92, 115, 178, 198, 218, 219, 310 Isoenzyme, 183, 310 Isotretinoin, 126, 310 J Jaundice, 8, 200, 201, 202, 203, 212, 243, 256, 303, 305, 310, 321 Jejunostomy, 291, 310 Joint, 267, 295, 310, 325, 332, 349, 350 K Kallidin, 192, 272, 310 Kallikreins, 310 Kb, 232, 311 Keratin, 83, 98, 311 Ketoacidosis, 89, 311 Ketone Bodies, 285, 311 Ketosis, 285, 311 Kidney Disease, 154, 156, 171, 212, 232, 237, 245, 311 Kidney Failure, 9, 290, 311 Kidney Failure, Acute, 311 Kidney Failure, Chronic, 311 Kidney stone, 311, 326, 356 Kinesin, 78, 311 Kinetics, 49, 312 L Labile, 280, 312 Lactobacillus, 47, 106, 142, 312 Lanthanum, 48, 312 Laparotomy, 23, 312 Large Intestine, 280, 286, 309, 312, 339, 345 Larynx, 312, 353 Latent, 38, 312, 333 Lavage, 68, 111, 158, 159, 209, 312 Laxative, 261, 289, 312 Lectin, 164, 165, 188, 189, 312, 316 Length of Stay, 139, 312 Lens, 162, 274, 312, 340

372 Pancreatitis

Leptin, 106, 182, 312 Lethal, 28, 35, 80, 269, 283, 312 Leucine, 64, 312, 328 Leucocyte, 88, 262, 291, 312, 315 Leukaemia, 136, 312 Leukemia, 82, 136, 143, 236, 297, 312, 333 Leukocytes, 45, 53, 65, 178, 187, 188, 271, 272, 276, 300, 309, 313, 354 Leukotrienes, 171, 174, 195, 266, 313 Library Services, 252, 313 Ligament, 294, 313, 335 Ligands, 165, 172, 313 Ligation, 8, 29, 45, 68, 70, 313 Linkage, 35, 36, 37, 154, 167, 313, 328 Lipase, 6, 7, 9, 12, 17, 18, 30, 59, 107, 149, 158, 161, 173, 179, 313 Lipid A, 164, 169, 313 Lipid Peroxidation, 128, 313, 326 Lipodystrophy, 27, 64, 313, 358 Lipolysis, 179, 313 Lipopolysaccharide, 129, 300, 313 Lipoprotein, 64, 119, 143, 164, 169, 175, 186, 187, 288, 300, 313, 314, 358 Lipoprotein Lipase, 119, 143, 313 Lipoprotein(a), 64, 313 Lipoxygenase, 313, 314 Liver cancer, 8, 29, 314 Liver Cirrhosis, 8, 147, 181, 192, 303, 314 Liver Neoplasms, 293, 314 Liver Transplantation, 199, 200, 201, 202, 203, 213, 314 Lobe, 265, 276, 314 Localization, 31, 63, 167, 192, 314 Localized, 19, 39, 55, 56, 163, 185, 295, 301, 307, 313, 314, 326, 331, 343, 355, 356 Locomotion, 314, 331 Longitudinal Studies, 36, 314 Loop, 172, 303, 314, 327 Low-density lipoprotein, 288, 313, 314 Lower Esophageal Sphincter, 292, 297, 314 Lumen, 56, 75, 78, 170, 314 Lupus, 188, 314, 350 Lutetium, 48, 314 Lymph, 47, 78, 269, 276, 290, 314, 315, 327, 348 Lymph node, 78, 269, 276, 314, 315, 327 Lymphadenopathy, 47, 314 Lymphatic, 290, 307, 314, 315, 317, 332, 346, 347, 352 Lymphatic system, 314, 315, 346, 347, 352 Lymphoblastic, 136, 315 Lymphoblasts, 260, 315

Lymphocyte, 77, 165, 177, 178, 259, 265, 315, 316 Lymphocyte Count, 259, 315 Lymphocytic, 47, 315 Lymphoid, 78, 265, 312, 315 Lymphokine, 47, 315 Lymphoma, 82, 132, 136, 142, 143, 145, 236, 315 Lysine, 315, 354 M Macronutrients, 16, 315 Macrophage, 29, 48, 50, 108, 309, 315 Macrophage Activation, 48, 50, 315 Magnetic Resonance Imaging, 19, 22, 26, 57, 100, 123, 315 Maintenance therapy, 81, 315 Malabsorption, 6, 20, 59, 71, 149, 173, 201, 202, 203, 236, 274, 315, 345, 358 Malabsorption syndrome, 201, 203, 315, 345 Malformation, 91, 315 Malignancy, 19, 76, 172, 315 Malignant, 37, 75, 236, 259, 260, 266, 267, 298, 314, 315, 319, 321 Malignant tumor, 315, 319 Malnutrition, 10, 18, 71, 261, 268, 272, 315, 320 Mammary, 313, 316 Mammogram, 273, 316, 317 Manometry, 118, 213, 316 Maximum Tolerated Dose, 66, 287, 316 Meat, 169, 193, 286, 316, 343 Mechanical ventilation, 5, 316 Medial, 267, 316 Mediate, 30, 32, 34, 55, 63, 65, 72, 74, 78, 186, 287, 316 Mediator, 29, 31, 48, 73, 77, 108, 176, 191, 277, 309, 316, 344 Medical Assistance, 242, 316 Medical Records, 50, 316, 342 Medicament, 177, 181, 192, 262, 316 MEDLINE, 233, 235, 237, 316 Melanin, 316, 330, 355 Melanocytes, 316 Melanoma, 236, 316, 355 Membrane Lipids, 316, 330 Membrane Proteins, 35, 316, 336 Memory, 78, 189, 265, 284, 316 Meninges, 275, 287, 316, 317 Meningitis, 174, 195, 317 Menstruation, 121, 317

Index 373

Mental, iv, 26, 156, 232, 234, 238, 275, 276, 284, 286, 294, 307, 316, 317, 337, 355 Mental Disorders, 156, 317 Meperidine, 21, 317 Mercaptopurine, 208, 317 Mesenchymal, 291, 317 Mesenteric, 4, 78, 185, 269, 275, 317, 333 Mesentery, 317, 329, 347 Metabolic disorder, 300, 317 Metabolite, 286, 317, 334 Metastasis, 8, 67, 181, 317 Metastatic, 37, 317, 343 Methionine, 49, 149, 178, 293, 317, 348 MI, 168, 169, 171, 193, 201, 213, 257, 317 Micelles, 173, 317 Microbe, 317, 353 Microbiology, 67, 260, 268, 317 Microcalcifications, 273, 317 Microcirculation, 24, 314, 317 Microglia, 267, 318 Micronutrients, 16, 318 Microorganism, 279, 318, 328, 358 Micro-organism, 301, 318 Microscopy, 35, 53, 55, 76, 269, 318 Microsomal, 64, 175, 318 Microspheres, 43, 318 Microtubule-Associated Proteins, 318, 322 Microtubules, 309, 311, 318, 322, 326 Migration, 108, 178, 188, 315, 318 Mineralocorticoids, 260, 283, 318 Mitochondria, 318, 320, 325 Mitomycin, 159, 318 Mitosis, 266, 318 Mobility, 48, 318 Mobilization, 183, 318 Modeling, 61, 64, 287, 319 Modification, 52, 202, 263, 285, 286, 298, 319, 338 Monitor, 18, 36, 45, 100, 319, 324 Monoclonal, 66, 162, 171, 304, 319, 338 Monoclonal antibodies, 162, 171, 319 Monocyte, 177, 178, 319 Mononuclear, 147, 319, 354 Morphine, 56, 126, 317, 319, 321, 325 Morphogenesis, 33, 319 Morphological, 35, 44, 123, 289, 316, 319 Morphology, 35, 47, 207, 274, 315, 319 Motility, 56, 112, 198, 200, 202, 204, 319, 344 Motion Sickness, 319, 321 Motor Activity, 282, 297, 319 Mucinous, 104, 115, 319

Mucociliary, 319, 345 Mucosa, 71, 296, 297, 314, 319 Mucus, 163, 319, 355 Multicenter study, 91, 319 Multigene Family, 165, 189, 319 Multiple Myeloma, 190, 191, 319 Multiple Organ Failure, 19, 176, 320 Multiple sclerosis, 161, 162, 168, 177, 178, 181, 207, 320 Muscle Fibers, 320 Muscular Atrophy, 236, 320 Muscular Dystrophies, 288, 320 Mydriatic, 286, 320 Myelin, 284, 320 Myelodysplastic syndrome, 190, 320, 345 Myelogenous, 320 Myeloma, 191, 320 Myocardial infarction, 4, 168, 175, 190, 192, 283, 317, 320, 358 Myocardial Ischemia, 192, 264, 320 Myocardial Reperfusion, 320, 340 Myocardial Reperfusion Injury, 320, 340 Myocarditis, 34, 38, 47, 174, 181, 195, 321 Myocardium, 264, 317, 320, 321 Myopathy, 38, 321 Myositis, 174, 195, 321 Myotonic Dystrophy, 236, 321 N Naive, 47, 321 Narcotic, 317, 319, 321 Nasogastric, 14, 18, 218, 291, 321 Nausea, 8, 10, 212, 243, 256, 296, 297, 307, 311, 321, 324, 355 NCI, 1, 37, 155, 231, 321 Neocortex, 321, 322 Neomycin, 70, 321 Neonatal, 203, 321 Neonatal Hepatitis, 203, 321 Neoplasia, 45, 74, 236, 321 Neoplasm, 104, 321 Neoplastic, 60, 75, 304, 315, 321 Nephritis, 174, 177, 178, 187, 188, 195, 321 Nephropathy, 162, 177, 178, 181, 200, 311, 321 Nephrosis, 303, 321 Nerve Endings, 69, 322, 324 Nerve Fibers, 259, 275, 322 Nerve Growth Factor, 66, 322 Nervous System, 57, 182, 189, 237, 259, 261, 263, 268, 275, 277, 279, 296, 299, 313, 316, 318, 319, 320, 321, 322, 323, 325, 329, 344, 349, 350

374 Pancreatitis

Networks, 37, 322 Neural, 57, 112, 114, 261, 263, 318, 322, 346 Neuralgia, 322, 333 Neuritis, 181, 322 Neurodegenerative Diseases, 161, 162, 269, 322 Neuroeffector Junction, 322 Neurofibrillary Tangles, 189, 322 Neurofilaments, 322 Neurogenic, 55, 69, 322 Neurogenic Inflammation, 55, 70, 322 Neuromuscular, 259, 322, 355 Neuromuscular Junction, 259, 322 Neuronal, 42, 56, 69, 322 Neurons, 48, 57, 70, 77, 279, 285, 293, 296, 321, 322, 323, 349 Neuropathy, 181, 200, 323 Neuropeptide, 72, 77, 323 Neuroretinitis, 323, 341 Neurotensin, 71, 323 Neurotoxic, 48, 323 Neutralization, 185, 323 Neutrons, 262, 323, 338 Neutrophil, 55, 106, 118, 128, 132, 191, 323 Neutrophil Activation, 191, 323 Neutrophil Infiltration, 55, 323 Nicotine, 7, 323 Nifedipine, 112, 130, 133, 323 Nitric Oxide, 42, 103, 136, 151, 181, 323 Nitrogen, 16, 186, 262, 264, 292, 295, 311, 324, 327, 354 Nociceptors, 77, 324 Nonulcer Dyspepsia, 13, 324 Norepinephrine, 261, 287, 323, 324 Nosocomial, 19, 202, 324 Nuclear, 49, 61, 131, 137, 141, 269, 281, 293, 296, 324, 338, 351 Nuclei, 56, 182, 262, 265, 281, 297, 298, 315, 318, 323, 324, 325, 337 Nucleic acid, 164, 166, 185, 189, 269, 273, 284, 285, 286, 298, 324, 334, 338, 342 Nucleotidases, 304, 324 Nurse Practitioners, 4, 324 Nutritional Status, 10, 64, 324 Nutritional Support, 13, 16, 19, 41, 200, 203, 297, 324 O Odour, 266, 324, 355 Office Management, 203, 209, 324 Oliguria, 311, 324 Omentum, 302, 324, 347 Omeprazole, 324, 336

Oncogene, 106, 236, 303, 325 Oocytes, 69, 325 Opacity, 274, 285, 325 Operon, 325, 340 Ophthalmologic, 287, 325 Opiate, 319, 325 Opium, 319, 325 Opportunistic Infections, 259, 325 Optic Disk, 285, 325 Optic Nerve, 323, 325, 326, 341, 343 Organ Culture, 325, 352 Organ Transplantation, 181, 325 Organelles, 39, 48, 275, 284, 311, 316, 325, 331 Osmotic, 261, 325, 344 Osteoarthritis, 164, 168, 181, 190, 191, 193, 325 Osteomyelitis, 174, 195, 326 Osteoporosis, 161, 162, 168, 181, 292, 326 Outpatient, 8, 10, 19, 28, 326 Ovalbumin, 48, 326 Ovaries, 301, 326, 344 Ovary, 72, 292, 326 Overdose, 296, 326 Oxalate, 200, 326 Oxidation, 259, 266, 284, 285, 313, 326, 351 Oxidative metabolism, 44, 313, 326 Oxidative Stress, 35, 47, 49, 59, 127, 146, 326 P Pachymeningitis, 317, 326 Paclitaxel, 135, 144, 145, 326 Palliative, 57, 326, 351 Palsy, 189, 326 Pancreas Transplant, 60, 326, 327 Pancreas Transplantation, 60, 327 Pancreatectomy, 13, 21, 60, 107, 115, 215, 218, 327 Pancreatic Ducts, 59, 170, 290, 327 Pancreatic enzymes, 6, 19, 20, 40, 142, 185, 190, 327 Pancreatic Fistula, 20, 198, 201, 208, 327 Pancreatic Insufficiency, 20, 59, 149, 170, 204, 208, 327 Pancreatic Juice, 60, 68, 158, 160, 170, 185, 207, 222, 278, 297, 327 Pancreatic Pseudocyst, 20, 25, 91, 207, 327 Pancreaticoduodenectomy, 13, 21, 104, 327 Papilla, 123, 290, 327 Papillary, 104, 115, 327 Paralysis, 29, 327, 328

Index 375

Paranasal Sinuses, 327, 345 Parasite, 327, 354 Parasitic, 201, 203, 327, 342 Parasitic Diseases, 201, 327 Parenteral, 9, 16, 21, 71, 102, 143, 151, 202, 203, 208, 209, 327 Parenteral Nutrition, 16, 71, 102, 151, 202, 208, 209, 327 Paresis, 322, 328 Paresthesias, 322, 328 Paroxysmal, 236, 264, 328 Pathogen, 53, 301, 307, 328 Pathologic, 32, 36, 43, 67, 73, 121, 166, 207, 259, 266, 270, 282, 305, 328, 337, 357 Pathologic Processes, 266, 328 Pathologies, 48, 69, 163, 328 Pathologist, 62, 328 Patient Education, 242, 250, 252, 257, 328 Patient Selection, 7, 328 Pelvic, 56, 158, 159, 174, 195, 290, 328, 335, 341 Pelvis, 259, 311, 326, 328, 341, 356 Pepsin, 164, 328, 343 Pepsin A, 164, 328 Peptic, 50, 168, 181, 185, 200, 201, 203, 204, 212, 301, 328 Peptic Ulcer, 50, 168, 181, 185, 200, 201, 203, 204, 212, 301, 328 Peptide Chain Elongation, 278, 328 Peptide Hydrolases, 290, 304, 328 Percutaneous, 14, 25, 79, 186, 192, 329 Perforation, 184, 295, 329 Perfusion, 43, 158, 159, 306, 329 Perianal, 203, 329 Pericardium, 329, 350 Perineural, 10, 329 Periodontal disease, 161, 162, 329 Periodontitis, 298, 329 Peripheral blood, 37, 88, 191, 309, 329, 333 Peripheral Nervous System, 285, 291, 322, 323, 326, 329, 334, 346, 348 Peritoneal, 7, 9, 10, 14, 15, 25, 37, 158, 159, 209, 310, 329 Peritoneal Cavity, 159, 209, 310, 329 Peritoneal Dialysis, 9, 329 Peritoneal Lavage, 7, 10, 14, 15, 25, 159, 209, 329 Peritoneum, 317, 324, 329, 341 Peritonitis, 45, 159, 190, 199, 206, 329 Petrolatum, 289, 329 Pharmacokinetic, 62, 66, 329

Pharmacologic, 43, 76, 121, 165, 264, 329, 353 Pharynx, 297, 329 Phenolphthalein, 289, 330 Phenotype, 29, 39, 41, 49, 51, 67, 90, 98, 154, 330 Phenyl, 187, 317, 330 Phenylalanine, 328, 330, 355 Phorbol, 330, 336 Phorbol Esters, 330, 336 Phospholipases, 330, 345 Phospholipids, 31, 171, 175, 294, 308, 313, 316, 330, 336 Phosphoric Monoester Hydrolases, 304, 330 Phosphorus, 131, 273, 330 Phosphorylates, 58, 330, 336 Phosphorylation, 53, 58, 174, 195, 330 Photocoagulation, 279, 330 Photoreceptor, 162, 330 Phylogeny, 80, 330 Physical Examination, 4, 330 Physiologic, 7, 33, 34, 43, 57, 73, 77, 261, 278, 317, 318, 330, 335, 339, 344 Pilot study, 42, 50, 118, 119, 137, 139, 330 Pituitary Gland, 283, 294, 295, 330 Plague, 200, 330 Plaque, 38, 168, 264, 331 Plaque Assay, 38, 331 Plasma cells, 265, 319, 320, 331 Plasma Kallikrein, 192, 311, 331 Plasma protein, 261, 331, 333, 336, 344 Plasmin, 296, 331, 333 Plasminogen, 331 Plastids, 325, 331 Platelet Activating Factor, 19, 48, 331 Platelet Activation, 331, 345 Platelet Aggregation, 263, 295, 323, 331, 352 Platelet-Derived Growth Factor, 66, 332 Platelets, 323, 331, 332, 352 Platinum, 278, 314, 332 Pleated, 311, 332 Plexus, 275, 332 Pneumonia, 187, 188, 196, 282, 332 Pneumonitis, 174, 195, 267, 332 Poisoning, 296, 309, 321, 332, 343, 344 Polycystic, 237, 332 Polymerase, 32, 266, 332, 340 Polymorphic, 167, 277, 332 Polymyalgia Rheumatica, 193, 332 Polyposis, 280, 332

376 Pancreatitis

Polysaccharide, 265, 275, 332, 336 Polyunsaturated fat, 76, 332, 352 Port, 159, 332 Port-a-cath, 332 Portal Hypertension, 198, 200, 201, 203, 204, 332 Portal System, 49, 333 Portal Vein, 8, 332, 333 Posterior, 90, 263, 268, 275, 277, 287, 326, 333, 341, 343 Postherpetic Neuralgia, 181, 333 Postmenopausal, 292, 326, 333 Postnatal, 333, 347 Postoperative, 5, 8, 11, 116, 317, 320, 333 Postprandial, 8, 333 Postsynaptic, 322, 333, 345, 350 Potentiate, 29, 333 Potentiation, 60, 333, 345 Practice Guidelines, 12, 24, 234, 244, 333 Precancerous, 333, 334 Preclinical, 54, 66, 333 Predisposition, 20, 62, 333 Prednisolone, 81, 333 Preeclampsia, 168, 333 Prekallikrein, 331, 333 Preleukemia, 320, 333, 345 Premalignant, 70, 203, 333, 334 Preoperative, 5, 15, 334 Presynaptic, 57, 322, 323, 334, 350 Presynaptic Terminals, 322, 334 Prevalence, 13, 24, 208, 334 Primary Biliary Cirrhosis, 198, 199, 334 Primary Sclerosing Cholangitis, 199, 201, 208, 334 Prion, 189, 334 Probe, 277, 334 Problem Solving, 199, 334 Procaine, 130, 334 Proctocolectomy, 199, 334 Prodrug, 190, 191, 334 Proenzyme, 168, 334 Progeny, 281, 319, 334 Progesterone, 334, 347 Prognostic factor, 117, 334 Progression, 4, 13, 14, 19, 26, 45, 47, 53, 57, 75, 124, 127, 165, 178, 264, 334 Proinsulin, 77, 335, 338 Promoter, 40, 51, 70, 75, 100, 335 Prone, 49, 75, 335 Propanolamine, 191, 192, 335 Prophase, 325, 335, 349

Prophylaxis, 5, 21, 24, 87, 173, 187, 188, 209, 266, 335, 356, 358 Prospective study, 5, 122, 335 Prostaglandin, 7, 132, 196, 335, 352 Prostaglandins A, 171, 335 Prostaglandins D, 335 Prostate, 236, 270, 311, 335, 336, 354 Prostatic Neoplasms, 292, 336 Protease, 7, 52, 58, 64, 65, 76, 84, 111, 147, 158, 162, 164, 189, 280, 336, 342 Protease Inhibitors, 7, 64, 158, 336 Protein Binding, 61, 336 Protein C, 10, 39, 40, 68, 78, 158, 169, 192, 261, 263, 266, 269, 311, 313, 336, 355, 358 Protein Conformation, 263, 311, 336 Protein Kinase C, 58, 336 Protein S, 35, 39, 58, 73, 77, 165, 172, 189, 206, 237, 266, 271, 278, 292, 298, 321, 336 Proteinuria, 320, 333, 336 Proteoglycan, 191, 336 Proteolytic, 39, 43, 51, 192, 206, 207, 262, 280, 291, 294, 310, 331, 336 Prothrombin, 336, 351 Protocol, 28, 42, 46, 336 Proton Pump, 50, 325, 336 Proton Pump Inhibitors, 50, 336 Protons, 262, 304, 336, 337, 338 Proto-Oncogene Proteins, 326, 337 Proto-Oncogene Proteins c-mos, 326, 337 Protozoa, 281, 318, 337 Protozoan, 337, 354 Proximal, 170, 287, 332, 334, 337 Pseudocysts, 6, 19, 25, 167, 198, 208, 337 Psoriasis, 161, 162, 168, 171, 174, 177, 178, 187, 188, 190, 195, 220, 337 Psychic, 278, 317, 337, 343 Public Assistance, 316, 337 Public Policy, 233, 337 Pulmonary Artery, 271, 337, 357 Pulmonary Edema, 311, 337 Pulmonary Embolism, 337, 358 Pulmonary Emphysema, 161, 162, 337 Pulmonary Fibrosis, 177, 178, 337 Pulmonary Ventilation, 337, 341 Pulse, 243, 319, 337 Pupil, 282, 286, 320, 338 Purified Insulins, 335, 338 Purifying, 179, 338 Purines, 269, 338, 344, 359 Purpura, 117, 121, 338 Purulent, 259, 338 Putrefaction, 296, 338

Index 377

Pylorus, 21, 338 Pyogenic, 326, 338 Pyridoxal, 299, 338 Pyrimidines, 171, 269, 338, 344 Q Quality of Life, 11, 14, 18, 30, 62, 107, 114, 338, 349 Quiescent, 38, 338 R Race, 120, 318, 338 Radiation, 8, 176, 264, 291, 292, 295, 305, 338, 355, 359 Radiation therapy, 305, 338 Radioactive, 304, 319, 324, 338, 339 Radioactivity, 66, 338 Radioimmunoassay, 31, 56, 74, 338 Radiolabeled, 59, 66, 68, 338, 339 Radiological, 329, 339 Radiologist, 198, 339 Radius, 48, 339 Randomized clinical trial, 96, 106, 129, 142, 339 Reactivation, 38, 105, 339 Reactive Oxygen Species, 188, 339 Receptors, Serotonin, 339, 344 Recombinant, 33, 38, 45, 51, 54, 77, 161, 164, 173, 339, 357 Recombination, 55, 281, 297, 339 Reconstitution, 36, 339 Rectal, 140, 200, 226, 339 Rectum, 266, 272, 279, 280, 286, 295, 296, 307, 308, 312, 334, 335, 339 Recurrence, 17, 26, 121, 244, 339 Red Nucleus, 268, 339 Reductase, 50, 340 Refer, 1, 272, 280, 290, 294, 296, 314, 321, 323, 324, 340, 353 Reflective, 170, 340 Reflux, 202, 203, 292, 297, 340 Refraction, 340, 346 Refractory, 7, 141, 288, 340 Regeneration, 33, 71, 127, 143, 294, 339, 340 Regimen, 66, 288, 340 Regurgitation, 292, 297, 301, 340 Relapse, 63, 340 Relaxant, 295, 340 Remission, 315, 339, 340 Renal Artery, 305, 340 Renal failure, 21, 162, 303, 340 Reperfusion, 19, 52, 65, 168, 320, 340 Reperfusion Injury, 19, 168, 340

Repressor, 61, 325, 340 Reproductive cells, 298, 303, 340 Research Design, 60, 340 Resection, 8, 20, 21, 31, 33, 71, 114, 117, 218, 219, 340, 345 Resolving, 32, 340 Respiration, 273, 318, 319, 326, 340, 341 Respirator, 316, 341, 357 Respiratory distress syndrome, 17, 49, 131, 181, 187, 188, 341 Respiratory failure, 341, 357 Respiratory System, 165, 261, 319, 341 Restitution, 71, 341 Restoration, 164, 320, 339, 340, 341, 359 Resuscitation, 15, 25, 341 Retina, 277, 285, 312, 323, 325, 341, 342, 356 Retinal, 281, 285, 325, 341 Retinitis, 168, 341 Retinoblastoma, 236, 341 Retrograde, 23, 26, 183, 341 Retroperitoneal, 11, 79, 83, 90, 116, 154, 341 Retroperitoneal Fibrosis, 83, 116, 341 Retroperitoneal Space, 341 Retrospective, 10, 36, 119, 222, 342 Retrospective study, 222, 342 Retroviral vector, 297, 342 Reversion, 342, 355 Rheumatism, 187, 188, 193, 342 Rheumatoid, 164, 168, 170, 178, 181, 190, 191, 193, 267, 279, 342 Rheumatoid arthritis, 164, 168, 170, 178, 181, 190, 191, 193, 267, 279, 342 Rhinitis, 168, 192, 342, 344 Ribavirin, 94, 342 Ribonuclease, 158, 342 Ribonucleoside Diphosphate Reductase, 305, 342 Ribose, 32, 260, 342 Rickettsiae, 342 Rigidity, 331, 342 Risk factor, 3, 4, 9, 11, 12, 26, 36, 50, 59, 76, 113, 172, 187, 201, 212, 335, 342 Risk patient, 7, 16, 342 Ritonavir, 64, 342 Rod, 269, 312, 330, 342, 343 Rotavirus, 53, 342 Roxithromycin, 85, 342 S Saliva, 342 Salivary, 78, 185, 202, 286, 327, 342, 348

378 Pancreatitis

Salivary glands, 202, 286, 342 Salmonella, 53, 111, 296, 343 Sanitation, 267, 343 Saponins, 343, 347 Saturated fat, 64, 343 Sclera, 277, 281, 343, 356 Scleroderma, 193, 267, 343 Scleroproteins, 311, 343 Sclerosis, 168, 189, 237, 266, 267, 279, 320, 343 Screening, 31, 36, 39, 45, 74, 162, 199, 209, 220, 278, 343 Secondary tumor, 317, 343 Secretin, 43, 108, 118, 257, 343 Secretion, 6, 9, 19, 23, 35, 40, 43, 55, 57, 58, 60, 64, 73, 78, 170, 175, 185, 186, 187, 200, 259, 273, 283, 285, 291, 297, 303, 308, 318, 319, 324, 327, 343, 344, 356 Secretory, 7, 21, 35, 39, 53, 56, 60, 78, 96, 110, 170, 322, 325, 343, 350 Sedimentation, 275, 332, 343 Segregation, 339, 343 Seizures, 328, 343 Semen, 335, 344 Semisynthetic, 278, 306, 342, 344 Senile, 18, 24, 326, 344 Sensibility, 263, 305, 344 Sensitization, 43, 67, 76, 344 Sepsis, 10, 17, 21, 42, 45, 65, 68, 101, 159, 186, 187, 188, 196, 269, 344 Septic, 97, 124, 164, 190, 196, 344 Septicemia, 40, 42, 169, 193, 344 Sequence Homology, 160, 344 Sequencing, 53, 301, 344 Serine, 111, 160, 162, 164, 179, 182, 194, 278, 290, 296, 310, 336, 337, 344, 348, 354 Serologic, 306, 344 Serotonin, 99, 323, 339, 344, 354 Serotypes, 267, 344 Serum Albumin, 10, 339, 344 Sex Characteristics, 260, 264, 344, 351 Sex Determination, 237, 344 Shivering, 344, 351 Shock, 28, 39, 45, 46, 55, 58, 97, 124, 129, 164, 176, 181, 190, 196, 243, 264, 304, 345, 354 Short Bowel Syndrome, 202, 345 Side effect, 27, 62, 225, 261, 270, 286, 305, 345, 349, 353 Sigmoid, 345 Sigmoidoscopy, 203, 345

Signal Transduction, 35, 68, 71, 172, 308, 345 Signs and Symptoms, 340, 345, 355 Sinusitis, 174, 195, 345 Skeletal, 264, 319, 320, 345 Skeleton, 259, 310, 335, 345 Smallpox, 345, 356 Smoldering leukemia, 320, 345 Smooth muscle, 177, 188, 192, 262, 263, 273, 281, 295, 303, 311, 319, 345, 348 Social Environment, 338, 345 Sodium, 185, 299, 300, 318, 345, 346, 349, 356 Sodium Bicarbonate, 185, 346 Sodium Channels, 346, 356 Soft tissue, 193, 271, 345, 346 Solid tumor, 264, 346 Solitary Nucleus, 268, 346 Solvent, 293, 299, 325, 346 Somatic, 260, 278, 318, 329, 346 Somatostatin, 60, 96, 128, 129, 132, 143, 346 Sound wave, 339, 340, 346 Soybean Oil, 332, 346 Spasmolytic, 192, 346 Specialist, 20, 246, 286, 346 Specificity, 12, 31, 42, 68, 72, 184, 261, 290, 334, 346, 348 Spectroscopic, 131, 346 Spectrum, 37, 41, 306, 318, 342, 346 Sperm, 264, 277, 298, 303, 340, 346 Sphincter, 11, 19, 118, 184, 185, 222, 312, 347 Spinal cord, 56, 77, 113, 259, 267, 272, 275, 277, 287, 316, 322, 323, 326, 329, 347, 349 Spleen, 29, 78, 123, 269, 315, 327, 347 Splenic Artery, 99, 347 Splenic Vein, 333, 347 Splenomegaly, 47, 347 Spondylitis, 186, 193, 347 Sporadic, 74, 111, 322, 341, 347 Stabilizer, 139, 145, 146, 347 Staging, 9, 26, 89, 347 Standard therapy, 209, 347 Stavudine, 116, 347 Steatorrhea, 14, 59, 209, 347 Stem Cells, 69, 70, 347 Stenosis, 5, 119, 347, 348 Stent, 90, 93, 123, 222, 347 Sterile, 25, 347 Sterility, 307, 347 Sterilization, 13, 347

Index 379

Steroid, 60, 83, 84, 188, 270, 283, 343, 347 Stimulant, 303, 310, 347 Stimulus, 42, 78, 293, 310, 322, 328, 347, 351, 353 Stool, 8, 279, 307, 312, 347, 348 Strand, 332, 348 Stress, 7, 9, 18, 19, 23, 29, 39, 45, 46, 47, 52, 131, 268, 283, 296, 321, 326, 333, 342, 348, 356 Stricture, 347, 348 Stroke, 156, 161, 162, 175, 189, 232, 274, 348 Stromal, 290, 348 Structure-Activity Relationship, 72, 348 Subacute, 59, 206, 307, 345, 348 Subcapsular, 104, 348 Subclinical, 19, 208, 307, 343, 348 Subcutaneous, 260, 288, 301, 313, 327, 348 Submaxillary, 291, 348 Subspecies, 346, 348, 356 Substance P, 132, 292, 317, 339, 343, 348 Substrate, 39, 183, 184, 194, 304, 348 Subtilisin, 194, 348 Suction, 14, 218, 348 Sudden death, 131, 348 Sulfur, 178, 317, 348 Sunburn, 174, 195, 349, 355 Superoxide, 47, 349 Superoxide Dismutase, 47, 349 Supplementation, 14, 50, 64, 143, 147, 209, 349 Support group, 144, 349 Supportive care, 4, 8, 18, 25, 167, 349 Suppression, 23, 48, 77, 121, 283, 349 Suppressive, 50, 349 Surfactant, 170, 349 Survival Rate, 63, 176, 349 Sweat, 41, 349 Sweat Glands, 349 Sympathetic Nervous System, 268, 349 Sympathomimetic, 177, 191, 287, 291, 324, 349 Symphysis, 276, 335, 349 Symptomatic, 25, 171, 327, 349 Synapse, 261, 322, 334, 349, 350, 354 Synaptic, 323, 345, 349, 350 Synaptic Transmission, 323, 350 Synergistic, 172, 350 Synovial, 171, 191, 350 Synovial Membrane, 350 Synovitis, 181, 350 Systemic disease, 143, 344, 350

Systemic lupus erythematosus, 181, 187, 188, 193, 279, 350 Systolic, 305, 350 T Tachycardia, 42, 269, 350 Tachykinins, 55, 350 Tachypnea, 42, 269, 350 Tacrolimus, 81, 350 Taurine, 178, 270, 350 Telangiectasia, 237, 350 Telecommunications, 281, 350 Telomere, 301, 350 Temporal, 132, 303, 332, 351 Tendon, 272, 351 Tendonitis, 193, 351 Teratogenic, 310, 351 Terminator, 285, 286, 351 Testosterone, 340, 351 Thalamic, 268, 351 Thalamic Diseases, 268, 351 Thalamus, 56, 286, 351 Therapeutics, 42, 66, 90, 140, 169, 180, 193, 227, 351 Thermal, 28, 286, 323, 351 Thermogenesis, 183, 351 Third Ventricle, 306, 351 Thoracic, 56, 128, 351 Thorax, 259, 351 Threonine, 182, 336, 337, 344, 351 Threshold, 163, 305, 351 Thrombin, 65, 121, 194, 294, 296, 332, 336, 351 Thrombocytopenia, 81, 331, 351 Thrombomodulin, 336, 351 Thrombophilia, 194, 352 Thromboses, 6, 352 Thrombosis, 8, 20, 65, 161, 162, 336, 348, 352 Thromboxanes, 266, 352 Thrombus, 283, 307, 320, 332, 352, 357 Thymus, 306, 315, 352 Thyroid, 133, 352, 355 Thyroid Gland, 352 Thyroiditis, 178, 352 Thyroxine, 261, 330, 352 Tissue Culture, 70, 352 Tissue Extracts, 207, 352 Tolerance, 77, 260, 299, 352 Tomography, 6, 101, 281, 352 Tone, 326, 352 Tonic, 292, 352 Tonicity, 302, 352

380 Pancreatitis

Tonus, 352 Tooth Preparation, 260, 353 Topical, 293, 304, 310, 329, 346, 353 Torsion, 307, 353 Total pancreatectomy, 327, 353 Toxaemia, 333, 353 Toxic, iv, 26, 44, 192, 281, 283, 284, 291, 306, 323, 353 Toxicity, 44, 59, 63, 159, 287, 289, 316, 353 Toxicology, 82, 136, 234, 353 Toxin, 290, 352, 353 Trace element, 16, 353 Trachea, 55, 272, 312, 329, 352, 353 Transcriptase, 286, 347, 353 Transcription Factors, 30, 32, 61, 63, 68, 70, 73, 353 Transcutaneous, 136, 147, 353 Transcutaneous Electric Nerve Stimulation, 136, 353 Transduction, 68, 71, 172, 345, 353 Transfection, 180, 271, 297, 353 Transfer Factor, 306, 353 Transferases, 300, 353 Translation, 26, 263, 292, 321, 354 Translational, 36, 37, 354 Translocating, 269, 354 Translocation, 43, 185, 269, 278, 292, 354 Transmitter, 259, 267, 287, 310, 316, 324, 354 Transplantation, 60, 81, 115, 121, 147, 198, 199, 201, 278, 306, 311, 354 Trauma, 15, 19, 20, 28, 42, 45, 68, 165, 176, 187, 188, 189, 196, 198, 243, 269, 276, 292, 301, 327, 329, 351, 354, 359 Triad, 179, 354 Trichomoniasis, 109, 354 Triglyceride, 64, 88, 175, 305, 354 Troglitazone, 173, 354 Tropism, 34, 67, 354 Tryptophan, 279, 344, 354 Tube-feeding, 40, 354 Tuberous Sclerosis, 237, 354 Tumor marker, 270, 354 Tumor Necrosis Factor, 19, 49, 74, 83, 100, 132, 188, 354 Tumor-derived, 31, 354 Tunica, 289, 319, 354 Typhimurium, 111, 355 Tyrosine, 58, 171, 172, 174, 195, 274, 287, 355 U Ubiquitin, 322, 355

Ulcer, 91, 168, 199, 287, 324, 328, 355, 356 Ulceration, 164, 355 Ulcerative colitis, 45, 49, 82, 102, 170, 190, 193, 199, 201, 202, 308, 334, 355 Ultrafiltration, 302, 355 Ultrasonography, 9, 18, 23, 26, 158, 213, 355 Ultraviolet radiation, 287, 349, 355 Unconscious, 264, 306, 355 Uracil, 338, 355 Uraemia, 327, 355 Urea, 187, 188, 311, 349, 355 Urease, 301, 355 Uremia, 165, 311, 340, 355 Ureters, 311, 340, 341, 355, 356 Urethra, 335, 356 Urethritis, 174, 195, 356 Uric, 262, 300, 305, 338, 356 Urinary, 12, 122, 177, 196, 220, 273, 285, 298, 307, 324, 355, 356, 359 Urinary tract, 196, 285, 356 Urinary tract infection, 196, 356 Urine, 8, 121, 160, 266, 271, 273, 291, 301, 302, 307, 311, 324, 326, 336, 355, 356 Urticaria, 168, 264, 356 Uterus, 276, 290, 301, 317, 323, 326, 334, 356 Uvea, 356 Uveitis, 168, 186, 190, 356 V Vaccination, 356 Vaccine, 226, 260, 336, 354, 356 Vaccinia, 77, 356 Vaccinia Virus, 77, 356 Vacuoles, 39, 290, 325, 356 Vagina, 276, 285, 301, 312, 317, 356 Vaginal, 109, 192, 356 Valproic Acid, 95, 129, 131, 356 Varicose, 163, 356, 357 Varicose Ulcer, 163, 356 Varicose vein, 356, 357 Variola, 356, 357 Vasculitis, 165, 327, 357 Vasoconstriction, 292, 357 Vasodilatation, 55, 310, 357 Vasodilator, 272, 287, 303, 320, 323, 357 Vasomotor, 292, 357 Vector, 77, 327, 353, 356, 357 Vein, 20, 264, 267, 310, 324, 332, 333, 347, 357 Venous, 6, 87, 267, 271, 272, 276, 336, 356, 357, 358

Index 381

Venous blood, 271, 272, 276, 357 Venous Insufficiency, 356, 357 Venous Thrombosis, 357, 358 Ventilation, 357 Ventilator, 22, 316, 341, 357 Ventricle, 282, 303, 337, 350, 351, 357 Venules, 271, 273, 317, 357 Vertebrae, 347, 357 Vesicular, 318, 345, 357 Veterinary Medicine, 233, 357 Vibrio, 277, 357 Vibrio cholerae, 277, 357 Villous, 275, 357 Viral Hepatitis, 53, 119, 198, 200, 201, 203, 204, 303, 358 Viral vector, 47, 358 Virion, 34, 358 Virulence, 353, 358 Virus Diseases, 266, 358 Visceral, 56, 112, 128, 268, 275, 329, 358 Visceral Afferents, 268, 275, 358 Vitamin A, 308, 358 Vitreous, 277, 285, 312, 341, 358 Vitreous Hemorrhage, 285, 358 Vitro, 32, 43, 52, 74, 302, 358

Vivo, 29, 31, 33, 34, 43, 47, 48, 52, 57, 59, 65, 70, 74, 77, 136, 138, 182, 194, 286, 297, 302, 307, 350, 352, 358 W Warfarin, 29, 358 Weight Gain, 293, 358 Whipple, 114, 117, 358 Whipple procedure, 114, 117, 358 White blood cell, 42, 260, 265, 268, 270, 307, 313, 315, 319, 320, 323, 331, 358 Withdrawal, 317, 358 Wound Healing, 294, 359 Wound Infection, 196, 359 X Xanthine, 262, 359 Xanthine Oxidase, 262, 359 Xenograft, 264, 359 X-ray, 256, 257, 274, 281, 290, 295, 316, 324, 338, 339, 347, 359 Y Yeasts, 296, 330, 359 Z Zymogen, 35, 43, 75, 78, 184, 278, 334, 336, 359

382 Pancreatitis

Index 383

384 Pancreatitis

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

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

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

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

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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

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

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Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

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

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

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

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

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