IOPSY 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., 1960Biopsy: 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: 0-497-00139-X 1. Biopsy-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.
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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 biopsy. 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 BIOPSY ....................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Biopsy.......................................................................................... 10 E-Journals: PubMed Central ....................................................................................................... 68 The National Library of Medicine: PubMed ................................................................................ 72 CHAPTER 2. NUTRITION AND BIOPSY ........................................................................................... 117 Overview.................................................................................................................................... 117 Finding Nutrition Studies on Biopsy ........................................................................................ 117 Federal Resources on Nutrition ................................................................................................. 118 Additional Web Resources ......................................................................................................... 118 CHAPTER 3. ALTERNATIVE MEDICINE AND BIOPSY ..................................................................... 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 122 General References ..................................................................................................................... 126 CHAPTER 4. DISSERTATIONS ON BIOPSY ....................................................................................... 127 Overview.................................................................................................................................... 127 Dissertations on Biopsy ............................................................................................................. 127 Keeping Current ........................................................................................................................ 128 CHAPTER 5. PATENTS ON BIOPSY ................................................................................................. 129 Overview.................................................................................................................................... 129 Patents on Biopsy....................................................................................................................... 129 Patent Applications on Biopsy................................................................................................... 162 Keeping Current ........................................................................................................................ 197 CHAPTER 6. BOOKS ON BIOPSY ..................................................................................................... 199 Overview.................................................................................................................................... 199 Book Summaries: Federal Agencies............................................................................................ 199 Book Summaries: Online Booksellers......................................................................................... 211 Chapters on Biopsy .................................................................................................................... 215 CHAPTER 7. MULTIMEDIA ON BIOPSY .......................................................................................... 219 Overview.................................................................................................................................... 219 Video Recordings ....................................................................................................................... 219 CHAPTER 8. PERIODICALS AND NEWS ON BIOPSY ....................................................................... 223 Overview.................................................................................................................................... 223 News Services and Press Releases.............................................................................................. 223 Newsletters on Biopsy................................................................................................................ 225 Newsletter Articles .................................................................................................................... 226 Academic Periodicals covering Biopsy....................................................................................... 227 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 229 Overview.................................................................................................................................... 229 U.S. Pharmacopeia..................................................................................................................... 229 Commercial Databases ............................................................................................................... 230 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 233 Overview.................................................................................................................................... 233 NIH Guidelines.......................................................................................................................... 233 NIH Databases........................................................................................................................... 235 Other Commercial Databases..................................................................................................... 237 APPENDIX B. PATIENT RESOURCES ............................................................................................... 239 Overview.................................................................................................................................... 239
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Patient Guideline Sources.......................................................................................................... 239 Finding Associations.................................................................................................................. 244 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 247 Overview.................................................................................................................................... 247 Preparation................................................................................................................................. 247 Finding a Local Medical Library................................................................................................ 247 Medical Libraries in the U.S. and Canada ................................................................................. 247 ONLINE GLOSSARIES................................................................................................................ 253 Online Dictionary Directories ................................................................................................... 258 BIOPSY DICTIONARY ................................................................................................................ 259 INDEX .............................................................................................................................................. 359
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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 biopsy is indexed in search engines, such as www.google.com or others, a nonsystematic 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 biopsy, 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 biopsy, 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 biopsy. 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 biopsy, 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 biopsy. 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 BIOPSY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on biopsy.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and biopsy, 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 “biopsy” (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: •
Survey of Current Liver Biopsy Practice Patterns Source: Journal of Clinical Gastroenterology. 35(1): 86-88. July 2002. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: Although the hepatitis C epidemic has increased the proportion of Hepatology in general gastroenterology practice, many clinicians express concern regarding the risks of percutaneous liver biopsy. This article reports on a survey of clinicians regarding their current liver biopsy practice patterns. The authors sent a questionnaire about liver biopsy practices to members of the Duke University Digestive Epidemiological Studies Consortium. The response rate was 112 of 157 physicians (71 percent). Nearly a third (29.5 percent, 33 physicians) reported that they do not perform
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liver biopsies. Reasons cited for not performing biopsies included concern about risks (72.7 percent), low reimbursement (66.7 percent), and logistical issues with space and recovery time (45.4 percent). Routine practice was biopsy without ultrasound in 53.2 percent, ultrasound marking by a radiologist or technician at the time of biopsy in 24.0 percent, previous ultrasound marking in 17.7 percent, and ultrasound marking by the gastroenterologist in 5.1 percent. For patients with hepatitis C, 76.8 percent of clinicians perform routine biopsies before treatment. The authors conclude that new approaches, especially in training programs, may be necessary to make clinicians more comfortable with this procedure. 3 tables. 19 references. •
Colonoscopy Plus Biopsy in the Inflammatory Bowel Diseases Source: Gastrointestinal Endoscopy Clinics of North America. 10(4): 755-774. October 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Biopsy of the colon is an important diagnostic tool in the investigation of the inflammatory bowel diseases (IBD). Colon biopsies are critical in helping to diagnose diarrhea, to distinguish different forms of colitis, to determine the extent of disease, and to determine if neoplasia (including cancer) has arisen in the setting of chronic colitis. This article reviews a number of scenarios where colon biopsies are of particular importance, such as biopsies in the patient with undiagnosed diarrhea, distinguishing different forms of inflammatory bowel disease (IBD), assessing disease extent and activity, differential diagnosis of and diagnosing other disorders superimposed on inflammatory bowel disease, neoplasia in patients with IBD, and colonic biopsy as a mirror of generalized gastrointestinal or systemic disease. One table summarizes the recommended locations and numbers of biopsies for different scenarios. The author concludes that to use colon biopsies most appropriately in patient management and to get the most mileage from them usually requires frequent clinician-pathologist interaction, often repeat endoscopy with biopsies at a different time, and the assessment of the biopsies in the clinical context. 1 figure. 3 tables. 94 references.
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Practice Guidelines for Liver Biopsy Source: Canadian Journal of Gastroenterology. 14(6): 481-482. June 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail:
[email protected]. Summary: Histological assessment of the liver by using biopsy remains important in the diagnosis and follow up of acute and chronic hepatic (liver) disease. This article offers practice guidelines for liver biopsy, as established by the Canadian Association of Gastroenterology (CAG). Liver biopsies may be obtained blind, i.e., by clinical estimation of organ location; by using radiological guidance with computerized tomography or ultrasound; via the transvenous (through the jugular or femoral veins) route in patients with contraindications to percutaneous (through the skin) biopsy; or via direct vision, surgically or laparoscopically in certain situations. The authors list the indications for liver biopsy and note that the prebiopsy workup of a patient should include informed consent, including an explanation of the risks of the procedure and the laboratory test results that can be obtained from the biopsy. Postbiopsy management should include a recording by the physician performing the biopsy of how many 'passes' were made, any medications administered, and any apparent complications. Contraindications to percutaneous liver biopsy include an uncooperative patient,
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impaired coagulation, severe uncorrected anemia, significant ascites, infection in the path of the needle, suspected extrahepatic biliary obstruction of high grade, cholangitis, echinococcal cysts, no safe unobstructed access route to biopsy, leukemia and myelofibrosis, and uremia. The authors conclude that with strict attention to the indications and contraindications, liver biopsy can be regarded as a safe and useful procedure. 2 references. •
Pediatric Gastrointestinal Mucosal Biopsy: Special Considerations in Children Source: Gastrointestinal Endoscopy Clinics of North America. 10(4): 669-712. October 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: In most disorders of the gastrointestinal (GI) mucosa that occur in both children and adults, the mucosal manifestations are the same. This article focuses on those disorders and the approaches to GI procedures and mucosal biopsy that are of a particularly or peculiarly pediatric nature (i.e., are different from those in adults). The authors discuss issues pertaining to endoscopy and other techniques of mucosal biopsy in children, because some approaches and techniques are considerably different from those in adults. In children as in adults, most mucosal biopsies are taken at upper GI endoscopy or colonoscopy, with rectal suction biopsy (RSB) being performed occasionally and blind esophageal suction biopsy very rarely. The authors caution that major problems can arise in pediatric endoscopy when children are approached and instrumented like adults. The authors describe the preparation of the child and family, sedation, bowel preparation, and fasting. The authors include a section discussing disorders in which there are special features in children that may be significantly different from adults, including gastroesophageal reflux disease (GERD), idiopathic eosinophilic esophagitis, Barrett's esophagus, Helicobacter pylori infections, Crohn's disease, allergic gastritis, celiac gastritis, chronic granulomatous disease, Menetrier's disease, neonatal gastropathies, Henoch Schonlein gastritis, cow's milk protein enteritis, microvillous inclusion disease, tufting enteropathy, autoimmune enteropathy, inflammatory bowel disease, pseudomembranous colitis, necrotizing enterocolitis, glycogen storage disease, Hirschsprung's disease, intestinal neuronal dysplasia, and colorectal cancer. 217 references.
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Role of Liver Biopsy in Chronic Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S152-S160. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The report of the 1997 National Institutes of Health (NIH) Consensus Development Conference on hepatitis C endorse pretreatment liver biopsy. This article reviews the role of liver biopsy in chronic hepatitis C, addressing whether liver histology helps determine the urgency of, and predicts the likelihood of response to, antiviral therapy; and if surrogate markers can supplant histological assessment. Because the rate of progression of chronic hepatitis C is influenced by baseline histological grade or stage, patients can be stratified into those with moderate to severe hepatitis, who merit imminent therapy, and those with mild hepatitis, in whom therapy can be postponed until more effective or tolerable treatments become available. Less advanced baseline histology has been shown to be an independent predictor of responsiveness to antiviral therapy. Although the predictive value of biopsy is
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insufficient to withhold therapy from patients with advanced fibrosis, baseline biopsy helps gauge expectations for the outcome of therapy. Reports have been published recently suggesting that laboratory markers can predict distinctions between low-grade fibrosis and therapy-indicating septal fibrosis or cirrhosis (scarring). These indices, however, are insufficiently reliable to predict histological distinctions in populations with varying prevalence of fibrosis or cirrhosis or to provide anything more than broad qualitative distinctions, far short of the potential information in a liver biopsy. For most patients, the value of pretreatment liver biopsy outweighs its risks, provides information about the urgency of treatment, and should be retained. The authors call for studies to identify noninvasive laboratory markers of histological activity and stage, especially genetic predictors of accelerated disease progression. 5 tables. 59 references. •
Small Intestinal Mucosal Biopsy for Investigation of Diarrhea and Malabsorption in Adults Source: Gastrointestinal Endoscopy Clinics of North America. 10(4): 739-753. October 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article examines the clinical use of small intestinal biopsy for investigation of diarrhea or suspected malabsorption problems. The author stresses that the use of small intestinal biopsy for diagnosis in these conditions depends on an optimal interaction between the clinician endoscopist and the pathologist. This necessitates open and interactive communication between involved physicians and an appreciation for correct tissue handling and biopsy orientation in the endoscopy unit and the pathology laboratory. Classification of biopsy changes on the basis of architectural abnormalities in the small intestinal biopsy may be helpful in defining the diagnosis and include severe (flat) or variably severe (mild or moderate) abnormalities. For some small intestinal disorders that are characterized by diarrhea or malabsorption, the biopsy findings may be distinctive and lead to a specific diagnosis. For others, like celiac disease, the changes are less specific, and it has become better recognized that an increasing number of conditions can produce similar histopathologic changes. Definition of typical gluten sensitive biopsy changes in this disorder is critical. 1 table. 72 references.
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Esophageal Biopsy Source: Gastrointestinal Endoscopy Clinics of North America. 10(4): 713-722. October 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article examines the role of endoscopic esophageal biopsy in the diagnosis of Barrett's esophagus (BE). Special considerations for screening and biopsy technique are discussed. The author reviews the value of esophageal biopsy and cardia biopsy in patients with reflux (when the stomach's gastric acid contents back up into the esophagus). Finally, the author reviews some of the features of the evaluation of infective esophagitis and esophageal cancer. Although biopsy is classically used to diagnose a lesion, an ulcer, or a stricture, it is being used with increasing frequency to screen patients with reflux. The usual purpose is to determine the presence of Barrett's esophagus and, when present, to assess the patient adequately for dysplasia (cellular changes that can be a precursor to esophageal cancer). The author concludes that
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esophageal biopsy has a high likelihood of diagnostic accuracy in malignant and infectious esophageal disease. With careful attention to landmarks and good communication between the gastroenterologist and the pathologist, BE should be readily diagnosed. Future research will be needed to determine the value of biopsy in the patient with gastroesophageal reflux and a normal endoscopy. 1 table. 25 references. •
Gastric Biopsy Source: Gastrointestinal Endoscopy Clinics of North America. 10(4): 723-738. October 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article focuses on the global settings where biopsy is done, on the practical issues of how to perform gastric biopsy, and what might be the benefit. The section on biopsy tips is condensed to provide practical information that offers some new information even for experienced endoscopists. The authors cover the three histological zones of the stomach (cardiac, oxyntic, and antral), when to biopsy to rule out neoplasia, and biopsy in benign gastric mucosal disease. The biopsy tips section covers a description of the biopsy location, special information needed for the pathologist, biopsy of histological zones, mapping the stomach, focal lesions, and acid suppression after multiple biopsies or large snare biopsy or polypectomy. At the time of biopsy of suspected or overt neoplasms, the endoscopist should try to determine whether tissue for special studies should be obtained; and whether the setting is such that biopsies from multiple sites might be indicated. The authors stress that there is a poor correlation between color changes and histologic abnormalities and emphasize that red mucosa is not reliably associated with gastritis, even though many clinicians insist on diagnosing gastritis on this inaccurate conclusion. 1 figure. 1 table. 57 references.
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Gastric Biopsy-Based Rapid Urease Tests for the Detection of Helicobacter Pylori: Progress, Advantages and Limitations. (editorial) Source: Journal of Gastroenterology and Hepatology. 17 (6): 629-632. June 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: This editorial comments on a study reported in this same issue of the Journal of Gastroenterology and Hepatology on the use of gastric (stomach) biopsy-based rapid urease tests for the detection of Helicobacter pylori. The gastric biopsy based rapid urease test has many advantages over other invasive methods: the test is simple to perform and the results are easy to read; the test is relatively inexpensive; and the test provides a prompt result (positive results occur within 1 hour in 53 to 99 percent of cases with H. pylori infection, allowing the initiation of the therapy soon after endoscopy for these cases). However, the gastric biopsy-based rapid urease tests also suffer from several limitations: they are invasive; they are not accurate in monitoring the effectiveness of eradication therapy; and less accurate results (including false-negative results) may occur, particularly in patients who are receiving treatment with antimicrobial agents or antisecretory drugs, in patients with bleeding peptic ulcers, and in children or the elderly. 1 table. 47 references.
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Principles of Skin Biopsies for the Family Physician Source: American Family Physician. 54(8):2411-2418. December 1996. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail:
[email protected]. Website: www.aafp.org. Summary: This journal article for health professionals provides guidelines for performing skin biopsies. Carefully performed skin biopsies are essential in the evaluation of many dermatologic conditions and lesions. Before beginning the biopsy, family physicians should understand a few guidelines regarding the choice of the lesion to be sampled. These guidelines help the physician avoid unnecessary scars and ensure optimal pathologic correlation. The most common techniques include the punch, shave, excisional, and incisional biopsies. Each procedure has advantages and disadvantages, depending on the dermatologic condition and the morphology of the lesion. Pigmented lesions characteristic of melanoma require special consideration. Techniques of skin preparation, tissue handling, anesthesia, and equipment are presented. 14 references, 5 figures, and 1 table. (AA-M).
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Which Technique To Biopsy or Remove a Skin Lesion? Source: JAAPA: Journal of the American Academy of Physician Assistants. 14(4): 5962,64,66. April 2001. Summary: This journal article provides health professionals with information on the techniques used to obtain skin tissue for laboratory evaluation of a skin lesion or to remove a skin lesion. The techniques most frequently used are punch, shave, and excisional. The technique depends on the location of the lesion, the potential for malignancy, the depth and size of the lesion, and cosmetic factors. The shave technique is generally the preferred method for obtaining tissue samples. However, this procedure is inappropriate on a pigmented lesion. If melanoma is highly suspected, an excisional procedure is the technique of choice. However, if the potential for malignancy in a pigmented lesion is low or moderate, the choice of procedure depends on the size. The shave technique is generally used if basal cell carcinoma is suspected, and the punch technique is appropriate if squamous cell carcinoma is suspected. The punch technique is appropriate if malignancy is not suspected but inflammation or infiltration is present. In the absence of inflammation or infiltration, the shave procedure is indicated. The article explains how to perform the shave and elliptical excisional techniques and discusses postsurgical care and complications. 5 figures, 1 table, and 5 references.
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Role of Liver Biopsy in Management of Chronic Hepatitis C: A Systematic Review Source: Hepatology. 36(5 Supplemental 1): S161-S172. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This review article considers two topics pertinent to the need for pretreatment liver biopsy in patients with chronic hepatitis C: how liver biopsy results predict treatment outcomes; and how well biochemical blood tests and serological measures of fibrosis predict biopsy findings in chronic hepatitis C. The authors searched MEDLINE and other electronic databases from January 1985 to March 2002. Additional articles were sought in references of pertinent articles and recent journals and by querying experts. Articles were eligible for review if they reported original human data
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from a study that used virological, histological, pathologic, or clinical outcome measures. Studies suggested that advanced fibrosis or cirrhosis (scarring) on initial liver biopsy is associated with a modestly decreased likelihood of a sustained virological response (SVR) to treatment. Also, studies relatively consistently showed that serum aminotransferases have modest value in predicting fibrosis on biopsy; that extracellular matrix tests hyaluronic acid and laminin may have value in predicting fibrosis; and that panels of tests may have the greatest value in predicting fibrosis or cirrhosis. Biochemical and serologic tests were best at predicting no or minimal fibrosis, or at predicting advanced fibrosis or cirrhosis, and were poor at predicting intermediate levels of fibrosis. Thus, evidence suggests that liver biopsy may have some usefulness in predicting efficacy of treatment in patients with chronic hepatitis C, and biochemical blood tests and serologic tests currently have only modest value in predicting fibrosis on liver biopsy. 2 tables. 81 references. •
Appropriateness of Liver Biopsy Source: Canadian Journal of Gastroenterology. 14(6): 543-548. June 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail:
[email protected]. Summary: This review article discusses the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The authors reviewed the medical literature, published between 1965 and 1999, by using MEDLINE. Only 0.1 percent of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heterogeneous opinions concerning the appropriateness of liver biopsy. Appropriateness should be evaluated for different techniques such as percutaneous liver biopsy, guided or not by ultrasonography, and the types of needles, automatic or not. The article reviews the evaluation of liver biopsy appropriateness in the real world, the adverse events and mortality of liver biopsy, and the appropriateness of liver biopsy in alcoholic liver disease and chronic hepatitis C. The authors conclude that liver biopsy is appropriate for a few diagnoses, and for the staging of chronic liver diseases such as alcoholic liver disease and chronic hepatitis C. However, excess use of liver biopsy, because of its cost and risk, may be a barrier to treatment. Underused liver biopsy may lead to inappropriate treatment of hepatitis. 3 figures. 1 table. 44 references.
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Cytomegalovirus DNA Identified in Skin Biopsy Specimens of Patients with Vitiligo Source: Journal of the American Academy of Dermatology. 35:21-26; July 1996. Summary: This study determined the presence or absence of viral genomes in the depigmented and uninvolved skin of patients with vitiligo. Researchers used a polymerase chain reaction assay to detect viral genomes in paraffinembedded skin biopsy specimens. Twenty-nine patients with vitiligo and 22 control subjects participated. Biopsy specimens were screened in a blinded fashion for a panel of DNA and RNA viruses included herpes simplex, varicella-zoster, cytomegalovirus (CMV), Epstein-Barr, HIV, and human T-cell lymphotropic virus. Results show that CMV DNA was identified in 38 percent of the patients studied. Twenty-one percent had indeterminate results. Results in all control subjects were negative. Polymerase chain reaction screening for identification of other viral genomes was negative. Although not statistically significant, data trends suggested a correlation between the presence of CMV DNA in biopsy specimens and active vitiligo of relatively brief duration. In
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addition, CMV-positive patients had a statistically significant increased frequency of other concurrent autoimmune diseases. The results suggest that vitiligo may indeed by triggered by a viral infection in select patients. 3 tables, 52 references. (AA-M).
Federally Funded Research on Biopsy The U.S. Government supports a variety of research studies relating to biopsy. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to biopsy. 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 biopsy. The following is typical of the type of information found when searching the CRISP database for biopsy: •
Project Title: 3D OPTICAL IMAGING AND DIGITAL X-RAY OF BREAST LESIONS Principal Investigator & Institution: Boas, David A.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: X-Ray mammography has contributed to a reduction in mortality due to breast cancer. It is inherently limited, though, as it is incapable of direct observation of physiological information relevant to the "functioning of cancer," which ultimately limits the specificity and prognostic ability of X-Ray mammography. Diffuse optical tomography (or tomographic optical breast imaging) is a promising imaging modality that provides information on the functioning and evolution of cancer - in particular, angiogenesis and hemoglobin oxygen saturation. It suffers, however, from limited spatial resolution relative to X- Ray, and this inhibits structural guidance and interpretation of the images obtained. This obstacle can be overcome by acquiring diffuse optical and X-Ray mammographic images "simultaneously" - that is, by combining the two modalities in a pioneering effort to overcome their respective limitations, mammography limited by specificity and optical limited by resolution, to produce a new multi-modality imaging method with enhanced specificity and prognostic value. We propose to advance the clinical utility of tomographic optical breast imaging by synergistically fusing the diffuse optical technology with state-of-theart digital X-Ray mammographic 3D tomography (known as Tomosynthesis), thus producing a multi-modality imaging method that integrates structural and functional information relevant to the screening and diagnosis of breast cancer. We believe that this combination will ultimately allow better differentiation of tumors through angiogenic and metabolic markers known to have prognostic value. During this grant period we
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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propose to further develop the optical technology and perform a clinical study to explore the optical sensitivity to detecting lesions already indicated by X- Ray, and the optical specificity to identifying malignant lesions as characterized by biopsy. This research project would not be feasible without the clinical research expertise of the Breast Imaging Research Lab, headed by Dr. Kopans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESOSPHAGUS
A
NOVEL
TECHNIQUE
FOR
SCREENING
BARRETT'S
Principal Investigator & Institution: Wang, Kenneth K.; Associate Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Gastroesophageal cancers are the most rapidly increasing cancer in Caucasian males and are a consequence of Barrett's esophagus. Barrett's esophagus is a pre-malignant condition that is produced by gastroesophageal reflux disease (heartburn). Screening for Barrett's esophagus can only be accomplished by endoscopy that is expensive and impractical given the population at risk. The purpose of this proposal is to design an "optical biopsy" system that can be applied by a wide range of health care providers to screen for Barrett's esophagus. This system will consist of an optical probe that can be placed into the esophagus with minimal discomfort to the patient that is connected to an optical biopsy console that will provide real time results. The primary design issues will be in constructing a small caliber probe that can be comfortably placed into the esophagus and yet expandable to provide contact with the esophageal wall for an optical biopsy. The second design consideration would be in constructing an algorithm that would analyze the spectroscopic signal from the "optical biopsy" which would distinguish normal and abnormal tissue in the upper gastrointestinal tract. Three proposed probe designs will be evaluated initially in the resected porcine esophagus and stomach to assess deployment of the probes and their safety. Subsequently, the probes will be assessed in the pig model to evaluate their performance characteristics. The best design will be selected for clinical testing. The clinical trials will involve the use of the probe in patients with known Barrett's esophagus and a control group undergoing endoscopy for other indications. The probe would be passed prior to endoscopy and the results compared to the endoscopic findings. The algorithms will be derived from optical and histological biopsies taken simultaneously at endoscopy from patients undergoing surveillance endoscopy for Barrett's esophagus. The development of a screening device for Barrett's esophagus that could be operated by paramedical personnel would enable large-scale low cost screening to identify patients at risk for esophageal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADIPOSE-RELATED BIOMARKERS OF PROSTATE CANCER Principal Investigator & Institution: Fowke, Jay H.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant) Adipocytes highly express the GYP19 gene encoding aromatase, an enzyme responsible for metabolizing androgens (e.g., testosterone) to estrogen (E). Estrogens activate estrogen and androgen receptors in prostate cells, and E exposure may permit cancer of the prostate (CAP) to progress to clinical detection and androgen-independence. Recently, a preliminary investigation found the Arg264Cys
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polymorphism in CYP19 associated with increased CaP risk, suggesting that body adiposity affects prostate carcinogenesis by altering the androgen/estrogen balance. However, epidemiologic studies provide little support for a relationship between obesity and CaP, perhaps because it is difficult to estimate body adiposity in large epidemiologic studies. Our multi-disciplinary team from the fields of nutritional epidemiology, pathology, medical genetics, molecular biology, and urology propose to investigate the role of adipose and estrogen related biomarkers in prostate carcinogenesis. Toward this goal, this pilot molecular epidemiologic study aims to recruit men undergoing confirmatory diagnostic tests for CaP. Fasting blood samples will be collected, and diet, physical activity, body size, and other CaP risk factors will be measured during pretreatment interviews. The recruitment base includes clinical centers serving the African-American population of Nashville, TN. With the endorsement of clinical staff we expect to recruit 70% of all biopsy patients at these centers, providing 250 CaP cases during one year. A control group (n=250), matched to the age and race distribution of the case group, will be selected from men without CaP at biopsy. Bias in the analysis may be reduced by excluding controls with latent CaP, systematic data collection by trained interviewers, and analysis of pre-treatment blood samples. The association between CaP and CYP19 genetic polymorphisms (Arg264Cys, allele length) will be investigated using multivariable logistic regression controlling for genetic susceptibility to adipocyte differentiation (the Pro12Ala polymorphism of peroxisome proliferator activated receptor- y2), body adiposity (blood leptin), insulin resistance (blood insulin and Cpeptide), diet, physical activity, and other potential CaP risk factors. Greater body adiposity may advance prostate carcinogenesis through an estrogen mechanism, and an analysis of adipose-related biomarkers may suggest that weight reduction would decrease CaP risk or improve prognosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADULT LIVE DONOR LIVER TRANSPLANT-A COMPARATIVE ANALYSIS Principal Investigator & Institution: Abecassis, Michael; Associate Professor of Surgery; Surgery; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):The shortage of available cadaver organs has prompted the transplant community to consider living donor liver transplantation (LDLT) as an effective alternative to cadaveric liver transplantation (CLT). The potential limitations of LDLT consist primarily of 1) the potential risk to an otherwise healthy donor, and 2) the uncertainty regarding graft and patient outcomes for LDLT as compared to CLT. The core project of this proposal will compare outcomes for recipients of LDLT to those of CLT, while addressing the potential complications to living donors. In addition, we propose to analyze two separate issues. First, we will evaluate donor hepatic steatosis in both LDLT and CLT. We will compare novel non-invasive measurements of steatosis in living donors with the current gold standard, a liver biopsy. We will compare the results of transplanting steatotic livers from living and cadaveric donors, assessing graft and patient outcomes in both groups. We will also evaluate the role of hepatic steatosis on liver regeneration in both the living donor and recipient. We hypothesize that outcome of transplantation in steatotic livers of LDLT is superior to results obtained in steatotic CLT recipients. This first aim will help design a decision algorithm for the use of steatotic livers in both CLT and LDLT while validating non-invasive measurements of hepatic steatosis. Second, we propose to address the potential role for LDLT in the multimodal management of hepatocellular carcinoma
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(HCC). Given the lack of randomized trials and large case series, this issue has been recently addressed in studies utilizing decision-modeling analysis. This second aim will provide clinical data to validate these studies, and will compare CLT, with its inherent waiting times, to LDLT, a strategy that theoretically eliminates waiting times. We hypothesize that the outcome of transplantation of HCC in LDLT is superior to results obtained with CLT. In the aggregate, these studies will define the efficacy of LDLT in the US, while a focus on both a donor issue (hepatic steatosis) and a recipient issue (the special problem of HCC) will help delineate the potential advantages of LDLT over CLT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE, VEGF, AND SKELETAL MUSCLE CAPILLARIZATION IN HUMANS Principal Investigator & Institution: Gavin, Timothy P.; Exercise and Sport Science; East Carolina University 1000 E 5Th St Greenville, Nc 27858 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Even in healthy aging, there are many physiological changes. Advanced age is a major risk factor for coronary and peripheral vascular disease. Aging results in significant changes in skeletal muscle, among these is a lower capillary supply, known as capillary rarefaction. A lower skeletal muscle capillary supply is associated with reduced exercise tolerance and reduced insulin sensitivity, which are both risk factors for cardiovascular disease. In general, aging reduces the ability of the organism to respond to different types of stress. Advanced age is associated with a defect in compensatory neovascularization in response to tissue ischemia, possibly through a reduction in vascular endothelial growth factor (VEGF) expression. Recent work suggests that VEGF is important for skeletal muscle capillary maintenance and the angiogenic response to exercise training, a controlled stress that is known to increase VEGF expression. We therefore hypothesize that VEGF expression is lower in old humans. In addition, we hypothesize that in response to the stress of exercise, exercise-induced VEGF expression is reduced in aged humans. To test these hypotheses, we will determine the resting levels of skeletal muscle VEGF from skeletal muscle biopsies in three groups: 18-25 yrs; 45-55 yrs; and 60+ yrs of age. We will then exercise subjects at 50 percent of their maximum for 1 hr on a bicycle ergometer; an intensity and duration that we have shown to increase VEGF mRNA 5-6 fold in young subjects. Isolated mRNA will be analyzed by Northern blot analysis. Proteins will be analyzed by Western blot. Capillarization will be evaluated by morphometric analysis of muscle biopsy samples. Analysis of variance will be used to determine differences between groups and conditions. Data obtained from these studies will provide necessary information for future R01 funding. Findings will be important as little is known concerning the effects of aging on neovascularization potential in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANATOMIC/FUNCTIONAL BREAST MRI MARKERS OF SERM EFFECT Principal Investigator & Institution: Schnall, Mitchell D.; Matthew J. Wilson Associate Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-JUL-2003 Summary: Recent results demonstrating the potential for Tamoxifen to reduce breast cancer risk have placed a premium on understanding the effects of selective estrogen
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receptor modifiers (SERM) on the breast. MRI is a new powerful tool capable of providing anatomic and functional information about the breast. This project is aimed at developing anatomic and functional markers of SERM effect on the breast. In this project, breast MRI examinations will be performed on patients that have entered the Tamoxifen trial outlined in project 1. MRI examinations will take place at three institutions close to sites participating in the Tamoxifen trial (UCLA, UPENN, Beth Israel Deaconess Medical Center). Imaging will be performed prior to and at six-month intervals after initiation of treatment, and during the one-year observation time. It is hypothesized that glandular volume and quantitative measures of enhancement will serve as measures of SERM effect. The development of surrogate markers to quantitate SERM effect in the breast is critical to evaluating potential chemo-preventive agents as well as identifying those patients who might best benefit from such treatment. In addition, core biopsy samples will be obtained from areas of the breast that demonstrate enhancement on MRI. In addition, core biopsy samples will be obtained from areas of the breast that demonstrate enhancement on MRI. These areas have a high likelihood of demonstrating a proliferative lesion. Histologic, immunohistochemical and LOH/CGH analysis will be correlated with Tamoxifen effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIMHC ANTIBODY EFFECTS ON ENDOTHELIUM AND MUSCLE Principal Investigator & Institution: Reed, Elaine F.; Professor; Pathology and Laboratory Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JAN-1999; Project End 31-DEC-2007 Summary: (provided by applicant): Accelerated transplant arteriosclerosis (TA), a manifestation of chronic rejection, is the leading cause of graft failure. The development of anti-HLA antibodies to donor HLA antigens is a major risk factor associated with TA. The overall goal of this proposal is to elucidate the signal transduction pathways that mediate HLA class I induced cell proliferation and the development of TA. Under specific aim #1, we will establish whether anti-HLA antibodies induce tyrosine phoshphorylation of focal adhesion proteins and assembly of signaling complexes via an actin cytoskeleton dependent pathway in endothelium and smooth muscle. For this, we will establish whether exposure of cultured endothelial cells (EC) and smooth muscle cells (SMC) to monoclonal anti-HLA antibodies and anti-HLA antibodies from transplant patients with chronic rejection is accompanied by FAK phosphorylation and the generation of FAK/Src/Paxillin signaling complexes. We will determine if the phosphorylation of focal adhesion proteins is accompanied by alterations in the organization of the actin cytoskeleton and in the assembly of focal adhesions. We will explore the role of ROK, MLC phosphatase and ERK as upstream components of the class I signaling pathway. We will also determine if class I signaling stimulates antiapoptotic signals by inducing tyrosine phosphorylation of PI3-kinase, Akt and Bad. Under specific aim #2, we will identify the signaling pathways leading to MHC class I induced FGF receptor translocation in EC and SMC. For this, we will determine the role of the actin cytoskeleton, phosphorylation of FAK, Src, paxillin and assembly of focal adhesions in class I mediated FGFR translocation to distinct subcellular locations using flow cytometry and confocal microscopy. We will also assess the importance of ROK, ERK, MLC phosphatase in class I mediated FGF receptor translocation. The contribution of the FGF receptor tyrosine kinase activity and ERK phosphorylation to class I induced cell proliferation will be established. Under aim #3, we will assess the expression of class
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I induced tyrosine phosphorylation, FGF receptors and anti-apoptotic proteins in clinical biopsy specimens from cardiac allografts with and without evidence of transplant arteriosclerosis. We will determine the correlation between protein phosphorylation events and protein expression with the incidence and time of onset of transplant arteriosclerosis and development of anti-HLA antibodies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASPIRIN, UGT1A6 GENOTYPE, AND COLON GENE EXPRESSION 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 2002; Project Start 13-MAY-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Colorectal cancers are thought to arise as the result of a series of molecular changes that transform normal epithelial cells into a colorectal carcinoma, with an adenomatous polyp as an intermediate step in this process. One way to reduce mortality from this cancer involves the use of oral agents that prevent neoplasms from developing in the large bowel. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the incidence of colon adenomas as well as carcinomas by approximately 50 percent. Enzymes prominently involved in metabolizing aspirin are UDP-glucuronosyltransferases (UGT). UGT1A6 is a polymorphic UGT and its variant alleles metabolize aspirin less efficiently. We showed that in NSAIDs users, and aspirin users in particular, the risk for colon neoplasia is reduced only in individuals who are UGT1A6 heterozygous and homozygous variant, but not homozygous wild-type. Aspirin and its metabolite, salicylic acid, can inhibit growth through the inhibition of cyclooxygenases (catalysts of prostaglandin synthesis), the promotion of apoptosis, and other as yet unidentified pathways. The goal of this project is to determine the effect of UGT1A6 genotype on aspirin metabolism and on aspirin-induced changes in colonic gene expression and protein markers of apoptosis (Bax and Bcl-2). We propose to study: 1) urinary excretion of aspirin metabolites in 380 healthy individuals with different UGT1A6 genotypes in a cross-sectional study and 2) changes in colon gene expression induced by aspirin supplementation in a randomized, placebo-controlled trial of 40 individuals who are either homozygous wild-type or homozygous variant for UGT1A6. We hypothesize that in slow metabolizers the proportion of glucuronidated metabolites is smaller and that a smaller proportion of the aspirin dose is excreted within a specific time. Alterations in colonic gene expression will be determined using cDNA microarray analysis of biopsy RNA from the sigmoid colon and rectum and Bax and Bcl-2 expression in the colonic crypts will be measured by immunohistochemistry. We hypothesize that expression of e.g. growth-promoting genes will be reduced and apoptotic genes increased during aspirin use and that this reduction may be stronger in slow metabolizers than fast metabolizers. This project will also allow the identification of other genes whose expression is affected by aspirin supplementation. Ultimately, information obtained from this project will be useful in developing chemopreventive drugs that specifically target pathways involved in colon neoplasia. By targeting relevant pathways, side effects caused by the use of NSAIDs or specific Cox-2 inhibitors may be avoided. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BACTERIAL FLORA IN NORMAL ESOPHAGUS & REFLUX DISORDERS Principal Investigator & Institution: Pei, Zhiheng; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016
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Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Gastroesophageal reflux (GERD) is a chronic inflammatory disease affecting millions of Americans leading to the development of gastric/intestinal metaplasia (Barrett's esophagus), which is a precursor for adenocarcinoma (Ca). Although data from the stomach and colon suggest that colonizing bacteria are essential in inflammation-induced cancer development, little is known about esophageal bacterial flora. The long-term goal of this project is to define the role of bacteria in the progression of GERD to Barrett's esophagus and Ca. Our hypothesis is that bacterial flora exist in the normal esophagus, changing in the evolution of GERD into Barrett's esophagus and Ca. The specific aims are to: 1) define at a population level the bacterial flora in the normal esophagus and the esophagus with GERD-related diseases, 2) define at a species level the bacterial flora in the normal esophagus and GERD-related diseases, 3) determine host humoral immune responses to esophageal bacteria in patients with GERD-related diseases and controls. To define bacterial flora at a population level. The total number of bacteria per biopsy will be determined by quantitative real-time PCR using universal bacterial 16S rDNA primers with DNA from each biopsy. Specimens from disease groups will be compared for bacterial density (square mm mucosa). To define the flora at a species level, biopsies will be analyzed using sequence-based universal bacterial16S PCR and cultivation. PCR products will be cloned and sequenced, and species identification accomplished by comparing the sequences with kno\\0'D bacterial 16S sequences. Biopsies also will be cultured in anaerobic, aerobic, and microaerobic conditions, and colonies biochemically defined to a species level. Each disease group will be compared for the species identified and their prevalence. Cultivable whole cell bacterial antigens will be used in ELISA to determine whether the hosts recognize their presence. Serum antibodies also will be examined using immonoblots to identify disease-specific antigens. Significance: (i) Bacterial flora in the GI tract play important roles in pathologic conditions including inflammation and neoplasia. The esophagus is the only part of the GI tract where little is known about the bacterial flora, and the proposed study will assess the existence and complexity of the flora. (ii) While GERD initially results from chemical damage, bacterial overgrowth may promote intestinal metaplasia of the esophagus. The proposed study allows qualitative and quantitative examination of this hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BARIATRIC SURGERY RESEARCH CONSORTIUM Principal Investigator & Institution: Flum, David R.; Surgery; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Bariatric procedures offer sustained and significant weight reduction with the potential to effect general patient health, comorbid conditions, quality of life and the healthcare system. A Bariatric Surgery Clinical Research Consortium (BSCRC) wilt provide important prospective information about the true impact of the procedure on patients and opportunities to better explore the physiologic mechanisms that result in post-surgical weight loss. The BSCRC will prospectively collect clinical, demographic, epidemiological, laboratory and histological information. In addition to this database the BSCRC will complete the following studies: 1. A cross-sectional examination of the epidemiology of non-alcoholic steatohepatitis (NASH) in patients undergoing bariatric surgery and a prospective evaluation of the effect of surgically induced weight loss on the severity NASH and cellular markers of cytotoxic activity. There is a need for epidemiologic information about the prevalence,
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risk factors for, and impact of fatty liver disease in patients undergoing bariatric surgery. We propose a study to evaluate liver histology in a large group of patients undergoing bariatric procedures. Patients with evidence of NASH by biopsy will undergo subsequent liver biopsy at one year to determine if NASH improves with rapid weight loss. Patients with NASH who improve after weight loss represent an important model for evaluating the cellular mechanisms that are involved in the development of NASH. This study will evaluate markers of oxidative stress and hepatic mitochondrial structure to determine their relationship to NASH during and after rapid, surgical weight loss. 2. A prospective evaluation of the relationship between ghrelin, PYY3-36, appetite and weight loss outcomes after gastric bypass. Ghrelin and PYY3-36 are gutderived peptides that are involved in energy homeostasis principally through their effect on appetite. We propose a prospective study to determine the relationship of ghrelin and weight loss after gastric bypass and to determine if the degree of ghrelin suppression is correlated to hunger suppression and/or the amount of weight lost. This study will determine if inclusion of ghrelin producing cells in the gastric pouch is correlated to worsened weight loss outcomes. Lastly the study will begin to evaluate the relationship of PYY3-36 and ghrelin and determine if it is altered by or in response to the physiologic changes associated with gastric bypass. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BREAST CANCER HYPOXIA ASSESSED BY NITRIC OXIDE Principal Investigator & Institution: Chance, Britton; Professor; Medical Diagnostic Research Foundation Radnor, Pa 19087 Timing: Fiscal Year 2002; Project Start 16-JUL-2001; Project End 31-MAY-2004 Summary: (Applicant's Description) It is our intent here to lay the groundwork for a translational study of the efficacy of NIR optical method in deternining the level of hypoxia in human breast cancer by NIR optical spectroscopy and imaging. The test requires a gold standard of breast tumor hypoxia which is to be provided by pO2 deterninations where the instrumentation, expertise and technology is available at the Leipzig University while the expertise and technology for NIR spectroscopy and imaging is available at the University of Pennsylvania affording an opportunity for translational research. It is our intent to mobilize activities at these two locations in order that a initial test of 50 breast cancers can be made to validate that the spectroscopy and imaging of breast tumor hypoxia gives values comparable to those obtained with the gold standard of pO2 determination and that the tumor localization is consistent with other modalities particularly ultrasound, mammography and biopsy. Thus these studies require validation that these two groups can work together; the Philadelphia group providing instrumentation and personnel skilled in use of the instrumentation, whilst the Leipzig group will provide not only expertise in pO2 determination, ultrasound, biopsy, marnnography, but also the capability of making available a large population of high risk breast cancer patients who are willing to accept the complete protocol for breast cancer examinations. It is our intent to provide two types of NIR information: I) localized and quantitative spectroscopy of the desaturation of hemoglobin and the blood content in the same breast canceri region as that in which the pO2 deternination takes place. 2) A NIR imaging system which gives rapid and effective imaging of the deoxygenation of hemoglobin and blood concentration relative to nearby normal breast tissue. While the pO2 determinations and NIR hemoglobin spectroscopy and imaging currently afford the basis for calibration in models, the comparative study has never been done before in human breast cancers. If ourintended goals of
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demonstrating feasibility are achieved, then application for support through regular RO1channels would appear to be justified. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CATHEPSIN B IN PROGRESSION OF PROSTATIC LESION TO CANCER Principal Investigator & Institution: Sinha, Akhouri A.; Professor/Research Scientist; Genetics, Cell Biology & Develpmnt; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The prostate gland harbors many types of premalignant lesions (such as prostatic intraepithelial neoplasia: PIN, atypical adenomatous hyperplasia, AAH), but not all of them progress to prostate cancer (PC). When high-grade PIN (HGPIN) is found in a biopsy section, the pathologist suspects PC and the patient becomes a candidate for a repeat biopsy. The question arises: Which HGPINs are precursors to PC and which are not? Who should be biopsied repeatedly and who should not? Our central hypothesis is that cathepsin B (CB) and stefin A, and van Wildebrand factor VIII (vWF) are molecular markers that can distinguish HGPINs with the potential of progressing to PC from those that would not. We further hypothesize that immediate precursor HGPIN should be linked to a CB>stefin A ratio, increased microvessel density, wide spread degradation of basement membrane (BM) and local invasion of basal cells. Whereas, distant predecessor HGPIN and low-grade PIN (LGPIN) should be linked to CB<stefin A and/or CB=stefin A and decreased microvessel density. Our rationale is that, once biomarkers are linked to PIN types, they could be used in selecting patients for repeat biopsy. We will test our hypothesis using the Specific Aims: Aim 1: (a) Characterize the immediate precursor and distant predecessor HGPINs associated with PC in biopsy and/or transurethral resection of prostate (TURP) and prostatectomy samples of white and African American men. (b) Determine CB and stefin A proteins in laser capture (LCM) microdissected HGPINs by Elisa assay. Aim 2: Determine mierovessel density associated with HGPIN by quantitative image analysis of localized vWF. Identification of immediate precursor HGPIN to PC may lead to approaches for delaying or even preventing development of frank malignancy, thereby decreasing death due to this cancer. Our research is significant because the molecular marker criteria will aid selecting which patient with HGPIN in the initial biopsy/TURP will need repeat biopsy and thus, sparing those patients who do not from the associated trauma and pain and thus, reducing cost. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL STUDY OF ADV-TK RADIOGENE THERAPY FOR GLIOMA Principal Investigator & Institution: Aguilar-Cordova, Estuardo; Ceo; Advantagene, Inc. 160 Paulson Rd Waban, Ma 02468 Timing: Fiscal Year 2004; Project Start 07-JUN-2004; Project End 31-MAY-2006 Summary: (provided by applicant): Malignant gliomas have a very poor prognosis with median survival measured in months rather than years. It is a disease with great need of novel therapeutic approaches. Within cancer gene therapy the use of adenoviral vectors to deliver HSV-tk (AdV-tk) has been one of the most widely studied and promising approaches. A few dose escalation Phase I studies have shown good safety profiles with encouraging anecdotal results. However, its clinical efficacy has not yet been assessed
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for any tumor type. Thus, clinical Phase Il and Ill studies are needed to evaluate the true potential of AdV-tk. A completed phase I study of AdV4k + prod rug gene therapy in recurrent malignant gliomas demonstrated a safe dose range for AdV-tk in brain tumors and some encouraging results. Preclinical studies demonstrate improved efficacy without added toxicity when AdV-tk gene therapy is combined with radiation therapy. The current study proposed in this application seeks to evaluate the combination of AdV-tk + prodrug gene therapy in combination with radiation therapy for malignant gliomas. Since this radio-gene therapy combination has not previously been studied in human brain tumors, a Phase I study must first be performed to assess potential toxicity of the combination (the subject of this Phase I application). The long-term goal of the research described in this proposal is to develop a product that will increase survival time or quality of life for patients diagnosed with malignant gliomas. The patient population with unresectable malignant gliomas was chosen since these patients receive radiation therapy as standard of care following stereotactic biopsy for confirmation of diagnosis. In addition, no other local therapies are available for these patients. The primary objective for this Phase I study is to evaluate the safety of escalating doses of AdV-tk with a fixed dose of the oral prodrug, valacyclovir, and standard radiation therapy. Three dose levels of AdV-tk, ranging from 3x1010 to 3x1011 vector particles in half log increments, will be evaluated with 3-6 patients per dose. The study will be conducted by Advantagene, which has a track record of efficient translation of laboratory studies into clinical gene therapy studies, with patient accrual at the Massachusetts General Hospital (MGH), which has an active brain tumor clinical group. The Phase II portion will assess clinical efficacy at the maximum tolerated dose (MTD) or the highest dose level reached in this Phase I study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMBINED MR-PETT TOMOGRAPH FOR BREAST IMAGING Principal Investigator & Institution: Rubashov, Igor B.; High Medical Technologies, Llc 8023 Beverly Blvd, Ste 5-263 Los Angeles, Ca 900484523 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: MRI and PET have demonstrated their strengths in the diagnosis of breast cancer. In this proposal we bring the 2 modalities together and build on these strengths. The goal of this proposal is to develop a new breast imaging diagnostic instrument composed of magnetic resonance imaging (MRI) system and novel positron emission tomography (PET) scanner. The PET system will be placed inside the MRI magnetic field next to a breast magnetic coil. The integrated MRI-PET system will provide: MR(anatomic/nuclear molecular image), Nuclear (nuclear medicine based molecular image) and Combined (fused image) images without the necessity of moving the patient. Use of the combined modalities will allow obtaining very high sensitivity and specificity of diagnosed lesions during the same exam. The technological novelty of the proposed approach lays in the development of a novel PET system and new reconstruction software. The PET system will be built in a form of inexpensive small size ring scanner, which is not sensitive to magnetic fields present in the MRI systems. In the Phase I effort we will develop two PET scanner modules and processing electronics and reconstruction software. The two PET modules will be tested for operation in realistic conditions using MRI clinical system at UCLA. PROPOSED COMMERCIAL APPLICATIONS: In this proposal, we will build a small PET system for imaging the breast that can be used in the magnetic field of the MRI scanner. The market for these systems is expected to be in the 100's of millions of dollars. In addition, the combination MR-PET system could reduce the number of biopsies by giving unequivocal diagnosis
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for breast cancer in many cases that require biopsy today. The cost of one biopsy is approximately $3,000. Approximately 2 million biopsies are performed every year. This system could save $100's of millions of dollars annually. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Coutifaris, Christos; Associate Professor and Director; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Through this application, the University of Pennsylvania seeks to continue its participation in the network of clinical reproductive medicine units (RMU). The University has established strength in clinical and basic research in infertility, endocrinology and reproductive biology. High volume clinical programs in the surgical and medical treatment of female and male infertility have been in place for over three decades. Laboratories dedicated to reproductive medicine (assisted reproductive technologies, andrology, and reproductive endocrinology) and an NIH-supported Clinical Research Center enhance the clinical and research programs. The participating faculty brings expertise in gynecology, andrology, psychiatry, clinical epidemiology and biostatistics, clinical chemistry and computer and information technology. The proposed administrative structure for the RMU includes a Principal Investigator, Christos Coutifaris, M.D., Ph.D., Director of the Division of Reproductive Endocrinology and Infertility, who will be assisted by two co- principal investigators Luigi Mastroianni, Jr., M.D., previous director of the division and original P.I. of the Penn RMU and Kurt Barnhart, M.D., M.S.C.E., director of the division's clinical research unit. In addition, an Executive Committee will oversee the progress and functions of the RMU. During the previous period of funding, the first two clinical trials were completed and the initial analysis of the superovulation/intrauterine insemination (SO/IUI) protocol was published in the New England Journal of Medicine. Analyses of the fertile male study results and those of a number of ancillary studies stemming from the SO/IUI trial are currently being performed. If funding is extended, the University of Pennsylvania RMU will continue to recruit patients for the endometrial biopsy study (Penn's "concept protocol" in the previous submission) recently approved as a Network-wide protocol and will participate in any new studies decided upon by the steering committee and NICHD. It is anticipated that two additional years will be required for completion of the endometrial biopsy study. It is also anticipated that the protocol for the use of Methotrexate for treatment of ectopic pregnancy will be implemented in all RMN sites. With the recent establishment of a clinical research unit within the Division, which has dedicated space, equipment and personnel, the Penn RMU is in the unique position to undertake and successfully participate in multiple concurrent clinical trials. It is our expectation that as the Reproductive Medicine Network has now matured, multiple protocols will successfully be implemented. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--CLINICAL Principal Investigator & Institution: Tashkin, Donald P.; Professor of Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024
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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (Applicant's Abstract) The overall objective of the Clinical Core is to provide the personnel, physical resources and organization required to generate the clinical database and biologic specimens for projects I through 5. The Clinical Core will be responsible 1) for the design, implementation and execution of clinical research protocols within the SCOR, 2) for interactions between investigators in the various projects and 3) for data collection, data management and statistical analysis. A proposed clinical protocol incorporates state-of-the-art methods for diagnosis and treatment of idiopathic pulmonary fibrosis JPF) and assessment of its response to therapy. The specific aims are as follows: To execute clinical protocols involving patients with idiopathic pulmonary fibrosis. Recruit eligible patients with IPF from UCLA and its network affiliates in the Los Angeles area Acquire and review pre-screening data for initial assessment of study eligibility. Obtain informed consent, collect clinical data and perform pulmonary function testing Obtain and score chest radiographs and thoracic high resolution computerized tomographs Determine eligibility for enrollment into runin phase (prednisone therapy for 3 months) Repeat clinical, radiographic and physiologic assessments at specified intervals Determine eligibility for randomization and randomize eligible patients into the treatment phase Manage randomized patients on study treatment regimens (interferon -gamma [IFN-gamma] plus low-dose prednisone vs. azathioprine [AZAI plus low-dose prednisone), monitor toxicity and formally assess response to therapy at 3- month intervals using CRP assessment tools To procure lung tissue and bronchoalveolar lavage fluid and cells. Handle and transport lung biopsy specimens from IPF patients to the Tissue Pathology Core Perform fiberoptic bronchoscopy at randomization and at 6 and 12 months after initiation of study treatment and at the time of relapse in patients whose disease worsens after discontinuation of IFN-gamma or AZA. Handle and transfer bronchoalveolar lavage fluid and cells and transbronchial biopsy specimens to the Tissue Pathology Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPING NEW APPROACHES FOR CERVICAL CANCER CONTROL Principal Investigator & Institution: Kiviat, Nancy B.; Chief; Pathology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Invasive cervical cancer (ICC) is an AIDS defining disease [CDC Update, 1993]. Our studies show that women with HIV-2 or HIV- I infection are at increased risk of ICC and development of cervical intraepithelial neoplasia 3/carcinoma in situ (CIN 3/CIS). Screening programs based upon cytology, detection of human papillomavirus (HPV), and visualization of the cervix have all been proposed for use in resource poor settings, however, none of these methods are practical approaches to cervical cancer control in areas of endemic HIV infection. Novel approaches must be developed to identify and treat women at high risk for ICC in HIV endemic areas. We hypothesize that, in contrast to most HIV seronegative women who are infected with oncogenic types of HPV; HIV seropositive women co-infected with oncogenic types of HPV acquired the molecular changes which permit, and are associated with progression to ICC even before cytologic changes are detected, or when only mild changes such as CIN 1 are present. We further hypothesize that such molecular changes, which are predictive of increased ICC risk can be identified and could serve as the basis for sensitive and specific assays, with high predictive value, for the early identification of HIV, infected women at high risk of ICC. Our approach to
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developing relevant molecular assays is based on the knowledge that the set of expressed genes, or "expression profile" of normal cells differs from that of cancer and dysplastic cells of the same tissue type [Fields, 1994]. We propose to biopsy HIV seropositive and HIV seronegative women infected with oncogenic HPV types and with varying grades of cervical lesion abnormalities (CIN 1, CIN 2/3, CIS, ICC) and examine the expression profiles of these different lesions to identify changes in gene expression that are characteristic of malignancy but occur prior to ICC (i.e., in CIS). Once such profiles are identified, we will determine and compare the frequency with which abnormally expressed genes are present in earlier precursor lesions among HIV seropositive and HIV seronegative women. Validation on additional samples, and proof of principle testing on stored longitudinal samples from women who did and did not subsequently develop CIN 3/CIS, will be performed. This will provide the rationale for future development of "low tech" ELISA assays for detection of the protein products of the over-expressed genes of interest and for longitudinal studies demonstrating the utility of this approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIELECTRIC CHARACTERIZATION OF HUMAN BREAST TISSUE Principal Investigator & Institution: Hagness, Susan C.; Assistant Professor; Electrical and Computer Engr; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 05-FEB-2002; Project End 31-JAN-2005 Summary: The objective of the proposed research is to conduct a comprehensive set of measurements to determine the dielectric properties of malignant, benign, and normal breast tissues over a broad frequency range from 100 MHz to 20 GHz. The outcome of the proposed research will be the baseline data needed to test two hypotheses: a) there exists a systematic and significant contrast in the dielectric properties of normal breast tissue and malignant breast lesions at microwave frequencies, and b) there exists a systematic and significant contrast in the dielectric properties of benign breast lesions and malignant breast lesions at microwave frequencies. The data resulting from these measurements are needed to facilitate the engineering of non- invasive, non-ionizing microwave technology to complement and augment early detection, diagnostic, and treatment technologies presently employed in the detection and management of breast cancer. The long-term objective of our research is to improve breast cancer screening through the use of space-time microwave imaging as a complement to X-ray mammography. The data obtained from the proposed study will permit subsequent development of a practical microwave breast imaging system for clinical trials. The specific aims are: 1) To rigorously calibrate and test coaxial needle probes that will be used with a microwave vector network analyzer to obtain the dielectric permittivities and conductivities of freshly excised breast tissue samples for frequencies up to 20 GHz. 2) To measure at physiologic temperatures and moisture contents the dielectric properties of approximately 500 breast biopsy specimens and 60 breast reduction specimens. 3) To correlate the measured dielectric properties data with the complete surgical pathology reports for every breast biopsy and breast reduction specimen; the database will include fatty and fibroglandular normal breast tissue, benign tumors and proliferative lesions, and infiltrating and in situ carcinomas. 4) To conduct bioelectromagnetic dispersion analyses of the measured dielectric properties data and to assess the biophysical mechanisms for the observed contrasts (or lack thereof). 5) To conduct statistical analyses of the measured data to test the two tissue-dielectric-contrast hypotheses. This research will provide a scientific foundation for all future microwave
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technology development related to the breast in the 0.1 to 20 GHz range, whether for tumor detection, monitoring, or treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIET AND DURATION OF CERVICAL HPV INFECTION Principal Investigator & Institution: Goodman, Marc T.; Professor; None; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-OCT-2004 Summary: (Adapted from Investigator's Abstract) This project will establish a multiethnic cohort of women for long-term follow-up to identify factors that influence the persistence or resolution of human papillomavirus (HPV) infection of the uterine cervix. The specific aims are to 1) study the association of the dietary intake of fruits and vegetables, and the plasma levels of carotenoids, alpha-tocopherol, and vitamin C with HPV persistence; 2) examine the role of HPV type, quantity (viral load), and multiple (synchronous) HPV infections in HPV persistence; and 3) examine the interaction between nutritional (e.g., beta-carotene) and viral (e.g., HPV 16) factors on the risk of persistent HPV infection. A multiethnic cohort of 1,152 HPV-positive women, aged 18 and older, will be established among patients attending the obstetrics and gynecology clinics of three large medical centers in Honolulu. The cohort will include appreciable numbers of Asian (Japanese, Filipino, Chinese, Korean) Polynesian (Hawaiian, Samoan) and Caucasian women. The cohort will be followed longitudinally with the following data collected at baseline, month 4, month 8, month 12, month 24 and month 36 (6 visits): (a) a cervical cytological (Pap) smear for pathological review; (b) colposcopic visualization of the cervix for confirmation of cytology; (c) a cervical sample for HPV DNA analysis; and (d) a blood sample to measure micronutrient levels. An abbreviated questionnaire will be administered at baseline and an expanded interview will be conducted at month 4 including information on diet, tobacco and alcohol use, and sexual and reproductive history. A diet history and follow-up interview will be conducted at each annual visit. Cervical biopsy specimens obtained from cohort members will be reviewed by the study pathologist and sections will be archived at no cost to the present study. Analysis of the data will focus on the evaluation of dietary and plasma micronutrient levels and viral characteristics that influence the persistence of HPV infection using a generalized estimating equation (GEE) approach that corrects for the correlation between the repeated measures. The identification of these factors may provide insight into the natural history of HPV infection, and may improve our ability to characterize women who are at greatest risk for developing HPV-associated neoplasia. Such knowledge may also assist in the development of appropriate screening strategies involving HPV DNA detection that could be targeted at women who would benefit most from intensive follow-up. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DNA METHYLATION IN EARLY DETECTION OF PROSTATE CANCER Principal Investigator & Institution: Smith, Steven S.; City of Hope National Medical Center Duarte, Ca 91010 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: Prostate cancer (PCA) is the most commonly diagnosed cancer in American males and the second leading cause of cancer deaths. Current screening modalities are less than perfect, lacking the sensitivity and specificity for the optimal detection of
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organized confined potentially curable disease. Recent reports have identified two candidate markers for the early detection of prostate cancer: telomerase and methylation status. It is well established that the hallmarks of oncogenic transformation include general chromosome instability, widespread aberrations in cytosine methylation patterning and up-regulation of the telomerase system. A link between telomerase expression and chromosome stability has been recognized for some time, and links between chromosome instability and cytosine methylation have recently been firmly established. Our recent tumor biology studies suggest a link between telomerase overexpression and aberrations in methylation patterning. Thus, providing the basis for the use of these two markers in the detection of tumor and tumor progression. Our long term goal is to validate a set of markers of telomerase over- expression and local methylation change that can be used in providing a highly reliable test for detection and prognosis of prostate cancer using cells present in expressed prostatic fluid obtained from patients with elevated PSA and/or abnormal digital rectal exam (DRE). Our hypothesis is that methylation status at the androgen receptor gene, pi-class glutathioneS transferase gene GSTP1, L1 repetitive, or subtelomeric DNA sequences, or subtelomeric DNA sequences coupled with telomerase component levels in expressed prostatic secretion (EPS) will be reliable predictors of the presence or absence of prostate cancer. In addition, we believe that the methylation status of these various genes and sequences will provide prognostic information comparable to the Gleason's score on the prostate biopsy. EPS will be collected on all patients undergoing a TRUSP and biopsy for the evaluation of PCA. The EPS will be tested for the presence of the telomerase components and for the methylation patterns of the AR, GSTP1 gene, L1 repetitive elements and subtelomeric DNA sequences. We will combined the methylation results with the results of the EPS telomerase in patients with prostatic cancer and then compare this EPS profile to the stage and grade of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF SOMATOKINE IN MYOTONIC DYSTROPHY TYPE 1 Principal Investigator & Institution: Moxley, Richard T.; Professor; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: These phase 1 studies examine a possible new treatment for myotonic dystrophy type1 (DM1), the most common form of adult muscular dystrophy. At present no treatment exists to reverse its progressive wasting and weakness. Low levels of testosterone and growth hormone, as well as insulin resistance, appear to contribute to the muscle loss, but therapeutic trials to reverse these hormonal abnormalities have failed to produce significant improvement. A previous trial of insulin-like growth factor1 [IGF1] has offered promise. Treatment with rhlGF1 increased strength, protein synthesis, and insulin action in 7 patients but side effects caused 2 to drop out. A new, better tolerated, longer acting, preparation of rhlGF1, is now available from INSMED. It is SomatoKine, rhlGF1 in complex with recombinant human IGF binding protein 3, and it will be used in this proposal. Preliminary studies show it is safe and well tolerated in healthy adults, diabetics, and older women treated after hip fracture. We will evaluate SomatoKine in DM1. The aim of this proposal is to evaluate the safety and feasibility of daily subcutaneous injections of SomatoKine for treatment of muscle wasting and weakness by performing two sequential studies, each involving 15 patients with DM1: 1st) An initial 24-Week Dose Escalation Study of SomatoKine [0.5, 1.0, and 2.0 mg/kg, with each dose given daily for 8 weeks] to identify an "optimal dose" based upon the side effects, drug levels, and efficacy [dual energy x-ray absorptiometry (DEXA);
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quantitative myometry; manual muscle strength testing] observed at each dose; 2nd) A subsequent 24-Week study of SomatoKine using an "Optimal Dose" to demonstrate its safety and feasibility as a daily treatment for a six month period. In addition, we will search for evidence of altered signaling along the intracellular pathway for IGF1 by measuring phosphorylation of p70S6K in needle muscle biopsy specimens obtained from 10 DM1 patients in the 24-Week "Optimal Dose" SomatoKine Study and from 10 age-gender matched normal volunteers who will receive SomatoKine for only two days. Specimens will be obtained from vastus lateralis muscle before and after two days of "optimal dose" treatment. These studies will test our hypothesis that supraphysiologic levels of IGF1 are safe and well tolerated and provide preliminary data regarding efficacy (reversal of muscle wasting and weakness.) If the results of this project prove promising, we plan to carry out a larger, multi-center, phase 2, controlled trial of SomatoKine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGENS AND INSULIN RESISTANCE IN WOMEN Principal Investigator & Institution: Olefsky, Jerrold M.; Professor; Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by applicant): There are genetic and environmental causes of insulin resistance, and clearly these two inputs can be additive and interactive. A high fat intake is an important environmental factor which can cause, or exacerbate, insulin resistance and enhance the risk for the development of Type II diabetes. Our recent studies have shown that lipid/heparin infusions lead to insulin resistance in men, but not in pre-menopausal women. We also have preliminary data showing that postmenopausal women are fully susceptible to fat-induced insulin resistance and that estrogen replacement therapy re-establishes the protective state. In addition, we have conducted a series of studies in rats, demonstrating that estrogenization (endogenous or exogenous) will protect females from fat -induced insulin resistance. Based on these findings, we propose that men and non-replaced post-menopausal women will exhibit fat-induced insulin resistance, whereas, adequately estrogenized women will be protected. We will test these ideas, not only by employing the lipid/heparin infusion glucose clamp technique, but also by placing experimental subjects on control and high fat diets. It is also possible that adequate estrogen can ameliorate the effects of other physiologic causes of insulin resistance. Thus, we also will conduct studies to determine whether estrogenization can protect women from the insulin resistance induced by obesity and aging. Using muscle biopsy samples collected during the glucose clamp studies, we will conduct experiments aimed at identifying cellular mechanisms for these protective effects of estrogens. We also propose an extensive series of animal studies, in which we will explore in more detail the mechanisms of estrogen protection from fatinduced insulin resistance. We will conduct studies in normal male and female rats, ovariectomized rats, and old estrogen deficient female rats+/- treatment with estradiol, an estrogen antagonist, or estrogen receptor isoform specific agonists. Studies in mice with deletion of the alpha or beta forms of the estrogen receptor, as well as muscle specific estrogen receptor specific knockout animals are also proposed. We will also determine whether the fat cell secreted protein ACRP3O is modulated by estrogen status, and whether the insulin sensitizing effects of ACRP3O are responsible for the estrogen induced protection from insulin resistance. If the concepts contained in this application prove correct, then these findings could have significant implications
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concerning the mechanisms of insulin resistance as well as the treatment and possibly prevention of this disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL EFFECTS ON LIVER IN SELF-ADMINISTERING PRIMATES Principal Investigator & Institution: Cunningham, Carol C.; Professor; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Most protocols that employ animal models for studying the development of alcoholic liver disease utilize the rat that is being administered ethanol as part of the diet. These models have provided much of the information we presently have on the mechanisms that contribute to development of liver damage associated with alcohol abuse. To date there are no animal models where voluntary ethanol consumption has led to irreversible liver damage; i.e., damage past the fatty liver stage. The studies proposed in this application are designed to determine if non-human primates that are self-administering ethanol will demonstrate liver pathology predictive of the development of alcoholic hepatitis and fibrosis. Eleven Macaca fascicularis monkeys will be given free access to ethanol in drinking water for 1 year. These animals have been previously trained to drink ethanol voluntarily and some have consumed up to 4g/kg/day, which is equivalent to 16 drinks a day by a human. The heavier drinkers averaged blood ethanol concentrations of 170 mg/dl in a previous protocol. In the proposed studies, light, moderate and heavy drinkers will be included, which are comprised of 6 females and 5 males. Evidence for liver damage will be sought by analyses of blood samples, which will include measurements of yglutamyltransferase, aspartate and alanine transaminases, bilirubin, albumin, globulin and other blood components. Urinary concentrations of isoprostanes will be measured to screen for ethanol-related oxidative stress. Liver needle biopsy samples, taken every 3 months, will be examined by light and electron microscopy for indices of liver damage, such as hepatocyte ballooning, Mallory body formation, inflammation and fibrosis. lmmunohistochemical analyses will be implemented to measure levels of inflammation, apoptosis and stellate cell activation. The objectives of this study are 1) to determine if the self-administering M. fascicularis will develop liver pathology past the fatty liver stage and 2) to evaluate the efficacy of using blood and urine samples to follow development of alcoholic liver disease in an animal model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXERCISE, MUSCLE NUTRITIVE BLOOD FLOW AND ENOS IN AGING Principal Investigator & Institution: Hickner, Robert C.; Assistant Professor; Physiology; East Carolina University 1000 E 5Th St Greenville, Nc 27858 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Cardiovascular disease is the leading cause of death in the United States, with the incidence of cardiovascular disease increasing rapidly after 60 years of age. A primary risk factor for cardiovascular disease is hypertension, which also increases in prevalence in older individuals. Nitric oxide (NO) induced vasodilatation is reduced with age, resulting in increased blood pressure and reduced limb blood flow, particularly in light of the increased muscle sympathetic tone in older individuals. Impaired production of NO is also associated with peripheral vascular
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disease, insulin resistance, and Type 2 diabetes. However, there is some evidence that exercise training improves NO induced limb blood flow response at rest. The effect of exercise on the content of endothelial nitric oxide synthase (eNOS), the key enzyme in NO production, has not been investigated in muscle in vivo in humans. We hypothesize that there are reductions in eNOS expression and increases in muscle sympathetic tone in older individuals, resulting in reduced nitric oxide dependent skeletal muscle nutritive blood flow and alterations in muscle metabolism; furthermore, these ageassociated NO-mediated changes can be counteracted, or reversed, by endurance exercise training. We will investigate 24 (20-30 yr) sedentary individuals (men and women), as well as 24 sedentary older (60-70 yr) individuals (men and women) in the sedentary state, as well as after one day and seven days of endurance exercise training. Ten of these sedentary older individuals will also be studied after an additional seven weeks of endurance training. A muscle biopsy will be taken to measure eNOS content, and nutritive skeletal muscle blood flow will be monitored using microdialysis under resting conditions. These investigations will determine if endurance exercise improves nitric oxide dependent nutritive blood flow in skeletal muscle at rest, and will determine if this improvement is associated with increases in eNOS in skeletal muscle biopsy samples. The mediation of NO-dependent vasodilation by muscle sympathetic tone, endothelin, and prostacyclin will also be investigated. The long-term objectives of these investigations are: 1) to identify mechanisms responsible for a reduced nitric oxidedependent vasodilatation in older men and women and 2) to find practical means of reversing vasodilator decrements in older men and women, thereby reducing the incidence of cardiovascular-related diseases in this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY Principal Investigator & Institution: Kimonis, Virginia E.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2004 Summary: (Taken from the application): Limb-Girdle Muscular Dystrophy (LGMD) encompasses a clinically diverse group of disorders characterized by proximal muscle weakness first affecting the hip and shoulder girdle elevated creatinine kinase values, and non-specific changes in the muscle biopsy. In addition to clinical heterogeneity within the LGMD category, genetic heterogeneity is indicated by the existence of dominant and recessive forms. We have identified a large family with autosomal dominant LGMD and early onset Paget disease of bone (PDB). These individuals have bone pain in the hips, shoulders and back from the Paget disease. Individuals eventually become bed bound and die prematurely from progressive muscle weakness +/cardiomyopathy in their forties to sixties. Laboratory investigation indicates elevated alkaline phosphatase levels in affected individuals. CPK is normal to mildly elevated. Muscle biopsy of the oldest affected male revealed non-specific changes and vacuolated fibers. Preliminary molecular analysis excluded linkage to the known loci for the autosomal dominant and recessive forms as well as 2 loci for autosomal dominant PDB and 6 loci for cardiomyopathy. Exclusion of the candidate loci prompted a genome-wide scan of 39 family members (9 affected, 24 unaffected, 6 spouses} with 402 polymorphic microsatellite markers (Marshfield Genotyping Services). The disease locus was linked to chromosome 9p21-q21 with marker D9S301 (max LOD=3.64), thus supporting our hypothesis that this family displays a genetically distinct form of Limb-GirdleMuscular-Dystrophy associated with Paget disease of bone and cardiomyopathy. Subsequent haplotype analysis with a high density of microsatellite markers flanking
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D9S301 refined the disease locus to a 3.76 cM region on chromosome 9p21-13.2. This region excludes the IBM2 locus for autosomal recessive vacuolar myopathy. Two candidate genes mapped to the critical region, NDUFB6 and IL-11RA, are being examined for disease-associated mutations. NDUFB6 encodes a subunit of Complex I of the mitochondrial respiratory chain and the IL11RA gene product influences proliferation and differentiation of skeletogenic progenitor cells. Identification of the genes involved in the LGMDs has led to the elucidation of an entire family of proteins that function in the dystrophin-glycoprotein complex. and a basis for understanding the pathophysiology of this complex. Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION IN INFLAMMATORY MYOPATHIES Principal Investigator & Institution: Greenberg, Steven A.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): The goals of Gene Expression in Inflammatory Myopathies are: (1) to characterize patterns of muscle gene expression through the use of DNA microarrays among adult patients with distinct subtypes of inflammatory myopathies and correlate these patterns with clinical phenotypes, and (2) to formulate hypotheses relevant to the pathogenesis of the inflammatory myopathies. High-density oligonucleotide microarrays will be used to assay gene expression in muscle biopsy specimens from patients with inflammatory myopathies. These patients will be phenotypically well described and known to the clinical investigators of this proposal. Data analysis of gene expression profiles will be linked to clinical data to refine disease classification and understand distinctions among and within the major subtypes of inflammatory myopathy. Analysis of differential gene expression will also provide clues to pathogenesis of these disorders. This work may provide further diagnostic approaches to these disorders and contribute to the understanding of their pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE EXPRESSION PROFILES IN THE FAILING HUMAN HEART Principal Investigator & Institution: Lowes, Brian D.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by the applicant): The mechanisms responsible for progressive myocardial dysfunction and remodeling of the cardiomyopathic, intact failing human heart are unknown. The mechanism(s) behind Beta-blocker related improvements in myocardial function and reversal of remodeling also remains unknown. In general, the pathophysiologic mechanisms responsible for progressive myocardial failure and remodeling are likely to involve signaling mechanisms, which alter myocardial gene expression. Similarly, the molecular basis for improvement in myocardial function and remodeling following treatment with Beta-blocking agents also is likely due to timedependent changes in myocardial gene expression. Numerous recent studies have demonstrated that, in order to be meaningful, gene regulation and expression must be examined in the intact heart. The overall objective of this proposal is to identify, in human subjects with myocardial failure, gene expression profiles associated with changes in myocardial function. This proposal investigates 1) the expression of over
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12,000 genes in the failing human heart relative to nonfailing controls 2)changes in gene expression associated with Beta-blocker related improvement in myocardial function. Using microarray analysis we are able to measure the expression of a large number of genes in small quantities of human ventricular myocardium that can be obtained serially from the intact heart by right ventricular (RV) endomyocardial biopsy. We have demonstrated that in situations where left and right ventricular function are concordant, directional changes in gene expression are similar in RV free wall, RV septal endomyocardium, and LV free wall, indicating that RV septal endomyocardial biopsy samples may be used to investigate changes in RV or LV free wall gene expression. Thus, this proposal has the ability to determine the molecular mechanisms responsible for myocyte dysfunction in the intact human heart. Furthermore, this proposal has the ability to provide information relevant to the mechanisms responsible for Beta-blockerrelated improvements in myocardial dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION PROFILING IN AGING HUMAN SKELETAL MUSCLE Principal Investigator & Institution: Kandarian, Susan C.; Professor; Health Sciences; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2004 Summary: The age-related loss in skeletal muscle mass (sarcopenia) is associated with functional deficits and physical disability. Decreases in fiber size, and in contractile and metabolic capacity underlie the muscle weakness associated with senescence. Changes in gene expression with age represent a significant contribution to the functional defects. Newly developed oligonucleotide arrays are a powerful tool ideally suited for describing global changes in gene expression patterns with advance age. In the present application, we propose to examine in parallel the expression of thousands of genes in human skeletal muscle in response to aging using muscle biopsy samples and oligonucleotide-based DNA arrays. We propose to test the hypothesis that compared to young adult men, skeletal muscle from older healthy men will exhibit an upregulation of the stress response genes (heat shock response, DNA damage-inducible, oxidative stress-inducible), upregulation of genes associated with neuronal injury, and downregulation of the genes associated with energy metabolism (glycolysis, mitochondrial, and biosynthetic enzymes). In future work we will delineate the reversibility of age-associated changes by testing whether 12 weeks of progressive resistance training exercise will reverse the age-associated alterations in skeletal muscle gene expression. Alternatively, there may be age-related changes that are recalcitrant to "correction" or, new patterns of gene expression may result from training that counteract the functional deficits associated with aging. Differential gene expression with age and exercise will be analyzed by known gene functional category, and by similarity of gene expression change (i.e., cluster analysis). Genome- wide experiments will improve our understanding of biological processes by providing a comprehensive view of the molecular landscape in control vs. experimental tissue. The combined skills and expertise of Dr. Kandarian's and Fielding's laboratories lend themselves ideally to the study of the relationship between muscle function and genome-wide phenotypic changes. These investigators are invested in, and uniquely well suited to embark on this exciting collaboration using the expert application of molecular biological tools to the clinical problem of sarcopenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC MARKERS OF ACUTE PANCREAS ALLOGRAFT REJECTION Principal Investigator & Institution: Cashion, Ann K.; None; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2004 Summary: (provided by applicant): Aim: Acute rejection remains a major problem for pancreas transplant recipients and accounts for 30 percent of graft failures in the first year after transplantation, in spite of improved surgical techniques and advances in immuno suppression. There are no universally accepted clinical indicators of rejection for pancreas allografts. Biopsy proven rejection is the standard for diagnosis; however, pancreas biopsies may be technically difficult to perform and associated with risks to the recipient. Recently, increased cytotoxic lymphocytic expression of perforin, granzyme B, and Fas ligand in peripheral blood lymphocytes (PBL) has been associated with renal allograft rejection and may be indicative of subclinical acute rejection. Because of the increased incidence of acute rejection and the difficulty in establishing a clinical diagnosis, a similar technique to evaluate early markers of acute rejection is uniquely important in pancreas transplantation. We hypothesize that by measuring expression levels of 3 genes, perform, granzyme B, and Fas ligand, using a newly developed molecular technique (real-time reverse transcriptase polymerase chain reaction [RT-PCR]), we can noninvasively detect acute allograft rejection at the time or prior to development of biopsy proven rejection. The ultimate goal is to develop a reliable, non-invasive method to detect acute rejection, thus allowing for earlier therapeutic intervention and better outcomes in solitary pancreas recipients. Long-term, we aim to expand the use of this technology to identify other genetic markers for acute rejection and develop microarray chip technology to clinically monitor the immunological status of transplant recipients. Methodology: Over a 2-year period, 25 solitary pancreas transplant recipients will be entered into the study. At least 40 milliliters of blood will be obtained pretranspiant and at time of surveillance biopsies or clinic visits (10 time points). Peripheral blood lymphocytes (PBL) will be separated for mRNA extraction. State-of-the-art real-time RT-PCR (ABI PRISM 7700) will be used to quantify gene expression levels of perforin, granzyme B, and Fas ligand. T-tests will be used to examine differences in gene expression levels between those patients with and without hiopsv proven acute reiection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HCV COINFECTION
REPLICATION
AND
IMMUNE
RESPONSE
IN
HIV
Principal Investigator & Institution: Gretch, David R.; Associate Professor, Director Viral He; Laboratory Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: Coinfection with hepatitis C virus and HIV is not uncommon. Approximately 10 percent to 30 percent of HIV-infected individuals are also infected with HCV. Many natural history studies have found that those with coinfection have more significant, and more rapidly progressive, liver disease than HCV-infected individuals who are HIV-negative. While the pathogenesis of HCV liver disease is not well understood, many believe that the more advanced liver disease seen in those with coinfection is due to HIV-related immune deficiency. The specific aims of this proposals are as follows: Aim 1: To determine serum HCV RNA levels and quasispecies complexity and diversity
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in HCV-infected patients with and without HCV coinfection. This study will test the hypothesis that those with coinfection have higher HCV viremia and lower quasispecies complexity and diversity than those who are HIV-negative. Aim 2: To determine intrahepatic HCV RNA by in situ assay in HCV-infected patients with and without HIV coinfection. This study will utilize an in situ assay for genomic and replicative HCV RNA to test the hypotheses that intrahepatic HCV replication is increased in those with HIV and correlates with liver disease severity. It will also test the hypothesis that both HCV replication and liver disease are increased in those with more advanced HIVrelated immune suppression. Aim 3: To determine the effect of HAART on HCV viremia, quasispecies complexity and diversity, intrahepatic HCV replication, and the immune response to HCV. HIV infected patients who are to be treated with HAART will undergo liver biopsy for measurement of intrahepatic HCV replication both before and 12 months after initiating HAART. Other pre- and post-HAART measurements will include HCV viremia, HCV quasispecies complexity and diversity, an increase in intrahepatic staining for CD4 and CD8 cells, and an increase in peripheral lymphoproliferative responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEMORRHAGE EVACUATION EMPLOYING MR ENDOSCOPIC SURGERY TRIAL Principal Investigator & Institution: Martin, Neil; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: (provided by the applicant): Intracerebral hemorrhage is a devastating and disabling disease, with 30-day mortality rates estimated to be between 35-52%, and only 20% of survivors independent at 6 months. Surgical therapies, to date, have not been demonstrated to be effective for ICH in randomized, controlled trials, but studies have not focused on early and novel surgical procedures. Magnetic resonance-guided endoscopic surgical evacuation is a promising technique for the treatment of primary ICH, providing minimally invasive hematoma evacuation. Part A of this project proposes a single-center, randomized, controlled, blinded outcome evaluation, phase II clinical trial of MR guided endoscopic surgical evacuation vs. conventional medical management for treatment of primary ICH within 24 hrs of symptom onset, in 60 patients over 5 years. The central aim of this proposal is to demonstrate that early magnetic resonance (MR)-guided endoscopic surgical evacuation is a feasible, and potentially efficacious, treatment for patients with acute ICH. A signal of potential efficacy will warrant launch of a pivotal trial, and data gathered in this pilot will aid in selection of the endpoint analysis and additional aspects of a phase 3 trial. In this pilot trial, the primary study endpoint will be the modified Rankin Scale of gIobal disability at 90 days, analyzed dichotomously (proportion of patients alive and independent) and quantitatively. Multi-modal MRI, including diffusion-perfusion imaging, will be employed to monitor the evolving pathophysiologic changes occurring with ICH in both surgically treated and medically managed patients to better elucidate the processes involved in perihematomal injury and their response to therapy. Part B proposes a genetic analysis substudy, in which human brain tissue, obtained from endoscopic clot removal and peri-hematomal biopsy, will be analyzed to identify the molecular mechanisms of peri-hematomal damage. Gene expression patterns will be measured using qualitative, real-time RT-PCR on a hypothesized set of neurotoxic genes, and using cDNA arrays to screen for a larger set of genes important in the evolution of intracranial hemorrhage.
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Biopsy
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH ABNORMALITY
FAT
FEEDING
AND
INTRAMYOCELLULAR
LIPID
Principal Investigator & Institution: Guo, Zengkui; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: It is now known that intramyocellular triglycerides (imcTG) content in skeletal muscle of obese adults is increased and this abnormality is associated with impaired glucose metabolism in the muscle. However, the pathways responsible for the increase and the link between the increased imcTG and insulin resistance have not been studied in detail. The objective of this application is to determine the factors and pathways that are responsible for the imcTG accumulation, and to determine whether the oxidation of imcTG fatty acids is also increased and, if so, whether it directly affects glucose metabolism. It is hypothesized that elevated plasma insulin and fatty acid levels, as commonly seen in human obesity, independently stimulate imcTG synthesis and synthesis is the primary pathway leading to the increased imcTG accumulation; and that a larger imcTG pool leads to accelerated imcTG oxidation thereby interfering with muscle glucose metabolism. To test the hypotheses, three specific aims will be pursued to answer following questions: 1) Is insulin an anabolic hormone stimulating imcTG synthesis? 2) Does elevated plasma fatty acid concentration increase imcTG synthesis by providing abundant precursors? 3) Is a larger imcTG pool associated with accelerated oxidation of imcTG fatty acids, and if so, how this affects muscle glucose metabolism? A new one-pool model will be applied to determine the rates of imcTG synthesis, turnover and oxidation directly (muscle biopsy) at controlled insulin and fatty acid levels in rats made obese by high fat feeding. The oxidation of imcTG fatty acids and muscle glucose uptake, glycolysis and glycogen synthesis will be determined using multiple tracers to determine the effect of imcTG oxidation on glucose metabolism. Stable isotopic tracers (13C) and mass spectrometry (GC/MS and isotope ratio MS) will be used to quantitate the kinetics. These studies are designed to answer the questions whether an enlarged imcTG is a chemical entity that imposes a negative effect on glucose metabolism, and whether plasma insulin and fatty acids are responsible for the increased imcTG, and if so, how. Thus, the proposed research will improve the understanding of the mechanism of insulin resistance and imcTG abnormalities in the obese rat that will benefit investigation of human obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH TC SUSCEPTOMETER FOR MAGNETIC MEASURE OF BODY IRON Principal Investigator & Institution: Brittenham, Gary M.; Professor of Medicine; Pediatrics; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The proposed Bioengineering Research Partnership will integrate bioengineering, basic science and clinical efforts in the design, development and clinical validation of a high-transition-temperature (high Tc; operating at 77oK) superconducting susceptometer for the direct, non-invasive measurement of hepatic iron stores in patients with iron overload from hereditary hemochromatosis, thalassemia major, sickle cell disease and other disorders. Our laboratories originally proposed that storage iron (ferritin and hemosiderin) could be non-invasively assessed
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in vivo because of its paramagnetic properties. We subsequently developed lowtransition-temperature (low Tc; operating at 4.2oK) superconducting quantum interference device (SQUID) biosusceptometry as a clinical method for the measurement of hepatic iron stores. Non-invasive magnetic measurements of hepatic storage iron in patients with iron overload are quantitatively equivalent to biochemical determinations on tissue obtained by biopsy but the cost and complexity of the low-Tc instrument has restricted clinical adoption of the method. Our low-Tc susceptometer has three elements which utilize superconductivity: (i) the SQUID, (ii) the field coils that produce a localized steady magnetic field near the liver, and (iii) the detection coils and flux transformer. Recent technological advances make possible replacement of each of these low-Tc elements, cooled by liquid helium, with components able to function when cooled by liquid nitrogen. To provide "proof-of-principle," we have constructed and operated a prototype high-Tc susceptometer with (i) a high-Tc SQUID, (ii) a NdBFe permanent magnet providing a strong localized magnetic field, and (iii) detection coils and flux transformer fashioned from a high-Tc Y1Ba2Cu3O7-delta film deposited on a flexible substrate. The proposed Partnership will now optimize and integrate these components into a series of liquid nitrogen-cooled clinical devices, and then validate and certify the high Tc-susceptometers in studies of adult and pediatric patients. Magnetic studies permit accurate, direct, and repeated measurements of hepatic iron stores not possible with any other method. The development of an affordable, readily usable instrument for the non-invasive measurement of hepatic iron - a high priority goal of both the NIDDK and the NHLBI - would be a major advance in the diagnosis and management of patients with iron overload that would find immediate and widespread clinical use both in the U.S. and worldwide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HPV TESTING--SELF-COLLECTED SAMPLES FOR CERVICAL CANCER Principal Investigator & Institution: Koutsky, Laura A.; Professor; Epidemiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 21-JUN-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Human papillomaviruses (primarily HPV 16 and 18) play a central role in the development of in situ and invasive cervical cancer. The fact that most cervical intraepithelial lesions spontaneously resolve, along with the high costs incurred by follow-up of women with Pap smears showing atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesions (LSIL), has generated interest in the use of HPV DNA assays for managing women with cervical abnormalities. A large proportion of women in the United States do not undergo routine Pap smear screening according to recommended screening intervals, suggesting a need for an alternative, non-invasive method for cervical cancer screening. However, studies that have assessed the performance of self-collected screening methods for detection of high-grade cervical disease have been limited by generalizability, sample size, verification bias, and other methodological flaws. There has not been a large study in the United States to examine the possibility of using a selfcollected sample to test for HPV DNA as screening for CIN 2/3. The long term goal of the proposed study is to evaluate whether a self-collected test for oncogenic types of HPV could be used to screen women to detect CIN 2-3. Specifically, the study will (1) estimate the accuracy (e.g., sensitivity, specificity, detection rate, and false referral rate) of HPV DNA testing using self-collected vaginal samples relative to the accuracy of clinician-directed ThinPrep Pap smears for detecting biopsy-confirmed CIN 2-3, and (2)
34
Biopsy
estimate the accuracy of HPV testing of self-collected samples relative to testing of clinician-directed samples for detecting biopsy-confirmed CIN 2-3. The study will be conducted as part of the ongoing Evaluation of Cervical Cancer Screening Methodologies (EVA) project among a population of women attending Planned Parenthood of Western Washington (PPWW) clinics (Tacoma, Lakewood, and Federal Way). Approximately 2,400 women ages 18-55 will be screened throughout the course of the study. Those with (1) ASCUS, LSIL, or HSIL on Pap smear, (2) high-risk HPV DNA detected in self-administered or clinician-administered sampling, and (3) a 10% random sample of women with normal Pap smears and negative HPV DNA test results at the screening visit will be asked to return for a follow-up visit, which will include specimens for a ThinPrep smear and HPV testing and colposcopically-directed biopsy of cervical lesions. An accurate self-test for high-risk HPV types could have several important public health implications, by offering women (1) an alternative cervical screening method, (2) triage for equivocal Pap smears, (3) surveillance for recurrence after treatment for CIN 2 or higher, (4) testing for other STDs, and (5) reduced costs associated with office visits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFYING A VIRAL CAUSE OF MULTIPLE SCLEROSIS Principal Investigator & Institution: Lipton, Howard L.; Professor; Evanston Northwestern Healthcare Evanston, Il 60201 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (Adapted from applicant's abstract): Myelin breakdown in multiple sclerosis (MS) is mediated by me helper T Iymphocyte (T cell) Th1 subset by a process analogous with that of the animal model, experimental autoimmune encephalomyelitis (EAE). Extensive efforts have failed to show dear differences in T cell reactivity to candidate autoantigen peptides of myelin basic protein (MBP) and proteolipid protein (PLP) in individuals with MS compared to healthy controls. This suggests that a different pathogenetic mechanism may be operative. Considerable circumstantial evidence supports a role for a viral infection in MS, although an MS-specific virus has not been identified. Thus, the immunopathologic changes could be caused by a persistent central nervous system (CNS) viral infection with the immune response directed at viral rather than self proteins, but still mediated by the helper T Iymphocyte (T cell) Th1 subset as in EAE. The hypothesis is that a novel virus persists in the CNS to to drive the MS immunopathology. The putative virus replicates continuously in the CNS, driving continuous disease activity that underlies relapsing-remitting MS Viral replication may be similar to that in Theiler's murine encephalomyelitis virus (TME\/) infection in mice or Visna virus infection in Icelandic sheep, relevant experimental viral models of MS. Since the putative MS virus may be noncultivatable, transmission attempts to animals and molecular approaches provide the best means of its detection. Two previous attempts to transmit MS to non-human primates in the 1960s to 1970s were not optimal by current standards, and therefore should not dissuade current attempts. This proposal stands in contrast to studies focused on incriminating a specific known pathogen as a cause of MS. We propose to transmit MS to non-human primates by inoculating pairs of 0.5-1.0 year-old chimpanzees and squirrel monkeys intracerebrally (ic) with MS CSF mononuclear inflammatory cells (24 hr collection) and also with acute post-mortem plaques if optimum material becomes available. White matter lesions (serial cranial MRls), and CSF pleocytosis (serial cisternal taps) will detect subclinical disease in the animals. Stereotaxic biopsy will confirm the nature of developing lesions and enable serial brain-to-brain passage to demonstrate a replicating agent and its characterization.
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We also propose to construct and express MS CSF cDNA libraries in gt-11 as another way of detecting such a virus without prior knowledge of its nature. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF HIV ON HEPATITIS C INFECTION IN HEMOPHILIA Principal Investigator & Institution: Ragni, Margaret V.; Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 11-APR-2001; Project End 31-MAR-2005 Summary: (provided by applicant) The purpose of this study is to determine the impact of HIV infection on hepatitis C virus (HCV) liver disease outcome, and the prevalence, risk factors, and viral and immunologic characteristics of liver disease in HCV-infected hemophiliacs, both HIV(+) and HIV(-). Approximately 826 HCV-infected hemophiliacs from 10 U.S. hemophilia treatment centers will be available for study. This group is unique in that patients are well characterized, closely followed, the time of HCV infection is known, HCV infection duration is greater than 20 years, and the incidence of liver disease progression is increasing. The specific objectives of this study include: (1) a cross-sectional cohort study in which hemophiliacs with HCV infection, both HIV(+) and HIV(-), are enrolled and undergo transjugular liver biopsy to determine the prevalence of cirrhosis and fibrosis progression rate. (2) a cross-sectional study comparing HCV-infected patients, both HIV- and HIV+, to determine clinical, life-style, and laboratory, e.g. biochemical, serologic, molecular biologic, and immunologic characteristics associated with development of cirrhosis and stage of fibrosis progression. (3) a cytokine study, comparing cytokine mRNA levels, interleukin-6 (IL-6), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta 1 and TGF-beta 2) in liver tissue, cytokine immunoassay levels in plasma, and cytokine expression genotypes with liver histopathologic score and with fibrosis progression rate in prospectively-biopsied hemophiliacs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPROVING SCREENING & SURVEILLANCE IN BARRETT'S PATIENTS Principal Investigator & Institution: Tearney, Guillermo J.; Assistant Professor of Pathology; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Barrett's esophagus, also termed specialized intestinal metaplasia (SIM) of the esophagus, is the precursor to esophageal adenocarcinoma, a lethal cancer that is rising in incidence at an alarming rate. The longterm objective of this proposal is to decrease the mortality associated with esophageal adenocarcinoma. Evidence supports screening a large percentage of the adult population to identify patients with SIM. Regular surveillance of patients with Barrett's can then identify dysplasia and adenocarcinoma at an earlier, more treatable stage. The only accepted method for screening for SIM is biopsy through endoscopic guidance. Although this approach is well established, the vast majority (96-98%) of adenocarcinomas are found in patients without prior diagnosis of SIM. Important factors that contribute to the inadequacy of endoscopic biopsy for screening are cost and accuracy. The first goal of this work is to develop and test an accurate, less expensive screening method for Barrett's esophagus. We have previously demonstrated that optical coherence tomography (OCT) can accurately distinguish esophageal SIM from normal squamous epithelium in patients undergoing endoscopy. In the proposed
36
Biopsy
research we will develop methods for comprehensively screening the entire distal esophagus with OCT without requiring endoscopy or patient sedation. Current surveillance protocols consist of upper endoscopy with multiple random biopsies. Since dysplasia and adenocarcinoma are focal diseases, random biopsy is subject to sampling errors and high rates of false negative diagnoses. The second goal of this research is to develop and test a more sensitive method for surveillance in patients with Barrett's esophagus based on optically guided biopsy. Preliminary studies suggest that OCT can further differentiate SIM to identify dysplasia and adenocarcinoma. We propose to systematically image the entire Barrett's region and direct biopsy to locations that contain the most severe disease. The proposed work will expand the current diagnostic capabilities of OCT, develop a standalone imaging method for systematically evaluating the distal esophagus, and test these new methods for screening and surveillance in patients. This program will provide physicians with an improved diagnostic tool that will impact clinical practice as well as be used for future studies to address unresolved controversies regarding the natural history and treatment of patients with this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION
IN
VIVO
MOLECULAR
EFFECTS
OF
PROSTATIC
COX-2
Principal Investigator & Institution: Lin, Daniel W.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The proposal addresses the potential role of pharmacologic inhibition of the cyclooxygenase-2 enzyme (COX-2) for prostate cancer prevention or treatment, There is compelling evidence from in vitro experimental studies that inhibition of COX-2 decreases cellular proliferation, increases apoptosis, and modulates genes involved in cell cycle regulation. Additionally, observational epidemiologic studies find reduced risks of prostate cancer among men using nonsteroidal anti-inflammatory drugs, COX-2 inhibitors. One of the theories on how these compounds exert their effects is through protection from reactive oxygen species and subsequent DNA damage, while others have postulated that these agents modulate the cell cycle. Several groups currently are continuing intensive studies examining the in vitro effects of various COX-2 inhibitors on CaP cell lines or in CaP xenografts, however, no human experimental studies have examined the effects of COX-2 inhibitors on prostate tissue biology, This proposal is based on the hypothesis that COX-2 inhibition will reduce levels of intraprostatic prostaglandins, reduce oxidative stress, and modulate genes controlling the cell cycle in prostate tissue. The hypothesis will be tested in two double-blinded, placebo-controlled, randomized clinical trials to test effects of 25mg of the COX-2 inhibitor rofecoxib (Vioxx() on prostate biology: the first among men with a biopsy positive for cancer scheduled for prostatectomy within 6 weeks; the second among men with a prostate biopsy negative for cancer scheduled for repeat biopsy in 6 months. Tissues and blood collected at the initial biopsy will be compared with those collected post-treatment, allowing an assessment of both the acute (4 weeks) and chronic (6 months) effects of COX-2 inhibition. All analyses are based on modeling the treatment intervention effect, defined as the changes in cancer-related endpoint measures from baseline to follow-up in the active drug arm minus the placebo arm. The results of these investigations will clarify the impact of COX-2 inhibition on prostate biology, reveal mechanisms underlying the effects of COX-2 inhibitors on prostate cancer risk, and identify other pathways and targets for future primary and secondary prostate cancer prevention trials.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VIVO REGULATION OF PROTEIN TURNOVER BY HORMONES Principal Investigator & Institution: Nair, K Sreekumaran.; Professor of Internal Medicine; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-JUL-1989; Project End 31-JUL-2005 Summary: The prevalence of type II diabetes mellitus is rapidly increasing in the world at large and the management of this disease and its chronic complications has a major impact on health care expenses. The preliminary data indicates potential interactions between glucose and protein metabolism, which may play a key role in the pathogenesis of type II diabetes and its chronic complications. Little attention has been focused on this issue, however. Recent advances in biomedical mass spectrometry and protein purification will be applied to measure synthesis rates of individual proteins from needle biopsy samples and to measure tissue bed protein dynamics in both diabetic and control subjects. Although insulin anti-catabolic effect on muscle protein has been known for seven decades, the mechanism of this of this key insulin effect continues to be controversial. The current proposal addresses this issue by measuring the absolute muscle protein breakdown and synthesis from the isotope labels in amino acyl tRNA and intracellular compartment (combining muscle biopsy and microdialysis). Applying this approach, the P.I. will test a novel hypothesis that muscle protein breakdown adapts to the chronic insulin exposure by developing a resistance to insulin. Resistance to insulin-induced glucose disposal in muscle is reported to be inversely associated with the proportion of oxidative muscle fibers and mitochondrial oxidative capacity. The composition of muscle Myosin Heavy Chain (MHC) is a key determinant of muscle fiber type, which is reported to be genetically determined. The P.I. will determine whether people with type II diabetes have reduced synthesis rates and relative composition of MHC1 and 2A isoforms and a higher proportion of MHC2B. In addition, the investigator will determine whether the people with type II diabetes have reduced muscle mitochondrial protein synthesis, mitochondrial enzymes and capacity for ATP production, which could explain their increased muscle fatigability and reduced endurance capacity. The Principal Investigator (P.I) also seeks to determine whether the changes in synthesis and composition of MHC isoforms and mitochondrial functions response to exercise are less pronounced in people with type II diabetes. Groups of twenty people with type II diabetes and obese and lean controls will be studied in the baseline (sedentary) state and then after either three months of aerobic exercise training or placebo period. These studies will define more clearly the interaction between synthesis and expression of MHC isoforms, mitochondrial functions and insulin resistance to glucose metabolism. The P.I. expects that further advances in our understanding of mitochondrial protein synthesis and other protein turnover abnormalities in diabetes will be forthcoming from these experiments. These results will allow us to better understand the pathophysiology of this disorder and its chronic complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INFLAMMATION LEUKOENCEPHALOPATHY
/PROGRESSIVE
MULTIFOCAL
Principal Investigator & Institution: Koralnik, Igor J.; Associate Professor of Neurology; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007
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Biopsy
Summary: (provided by applicant): A controversy exists regarding the role of inflammation in PML. It has been suggested that an inflammatory reaction, demonstrated by contrast-enhancement of the CNS lesions on MRI or by lymphoplasmocytic infiltrates on brain biopsy may be beneficial in PML. This inflammatory reaction may be mediated by CD8+ cytotoxic T lymphocytes (CTL) that are specific for JCV. When detectable in the blood of PML patients, this cellular immune response is also associated with a favorable outcome. Recently however, cases of PML have been shown to develop in HIV+ patients shortly after introduction of HAART, in the context of inflammation associated with an immune reconstitution syndrome. Whether inflammation is harmful or beneficial in PML and if it should be treated with steroids is therefore not settled and has immediate clinical implications for the patients. We hypothesize that PML patients who have evidence of an inflammatory reaction on MRI/1H-MRS or on brain biopsy are able to mount a vigorous cellular immune response against JCV in their blood and CSF. They will develop smaller lesions and have a better clinical outcome. They will also be able to suppress JCV replication in their CSF, and control the emergence of more virulent isolates. Specifically, we will: 1) evaluate the inflammatory component and metabolism in PML lesions with contrastenhanced MRI and 1H-MRS, and correlate these findings with the cellular immune response against JCV in the patient's blood and CSF. 2) characterize the inflammatory infiltrates in PML lesions of those patients who undergo brain biopsy and analyze the topographic distribution of CD8+ T lymphocytes with regard to JCV-infected cells 3) quantify JCV CSF viral load of PML patients by qPCR to study the evolution of JCV replication in the presence or absence of inflammatory reaction. 4) analyze the sequence of JCV regulatory region (RR) in CSF of PML patients to assess the effect of JCV-specific cellular immunity on the emergence of JCV RR mutations and rearrangements 5) correlate MRI/1H-MRS, histological, immunological and virological parameters over time with lesion volume, neurological deficit and clinical outcome of the PML patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIVER TRIGLYCERIDE METABOLISM IN NASH Principal Investigator & Institution: Parks, Elizabeth J.; Food Science and Nutrition; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (adapted from the application) Non-alcoholic steatohepatitis (NASH) is a disease of emerging clinical significance. The risk factors for NASH include female gender, non-insulin dependent diabetes, obesity and hyperlipidemia. In NASH, the fat that accumulates in the liver is primarily triglyceride (TG) and three sources potentially contribute to this lipid are fatty acids (FA) derived from the diet, those originating in the adipose tissue (FFA in the plasma), and FA newly synthesized in the liver via process called de novo lipogenesis. The origin of the fat that accumulates in the liver has not been extensively investigated previously due to the technical challenges of studying de novo lipogenesis and the limitations of using radioactive isotopes in humans. Recent advances in gas chromatography/mass spectrometry and stable (non-radioactive) isotope methodology now make it possible to study hepatic TG metabolism in vivo. The hypothesis to be tested is that de novo lipogenesis contributes substantially to hepatic TG found in NASH. Further, it is hypothesized that plasma-derived FFA will contribute quantitatively less to the fat stored in hepatocytes and more to the TG that is exported from the liver in lipoproteins. Patients with persistently elevated liver enzymes of uncertain etiology, who are being considered for liver biopsy, will undergo a 5-day, stable-isotope infusion of labeled FA and precursors of FA, preceding the scheduled
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biopsy. Liver biopsy tissue (100 mg) will be analyzed to determine its biochemical content (TG, cholesterol, phospholipid and FFA), the composition of FA within these fractions, and the enrichment of labeled FA in the tissue (the sources of these FA). Control subjects will be aged- and sex-matched individuals undergoing surgical treatment for obesity who will have an identical isotope infusion before surgery. These methods will be used to accomplish the specific aims: (1) to quantify the concentration of the various lipids in NASH liver samples and samples from obese control subjects; (2) to determine the sources of FA used for lipid synthesis, and the turnover of these lipids in NASH patients and controls; and (3) to determine whether there is a difference between NASH patients and controls with respect to the composition of FA within liver tissue. Liver samples will be graded histologically and the stage of NASH documented semi-quantitatively. Computer tomography will be used to quantify liver size and abdominal visceral fat; ultrasound will also be performed. The results of all of these measurements will be analyzed to determine their relationship with hepatic lipid content. NASH will become more clinically important in the future as the incidence of obesity and diabetes continue to rise in the United States. In combination with the clinical data obtained, an understanding of the contributions of FA sources to liver TG will aid in the development of future treatment strategies for this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAMMOGRAPHIC DENSITY AS A PREDICTOR OF BREAST CANCER Principal Investigator & Institution: Mincey, Betty A.; Mayo Clinic Coll of Med, Jacksonville Mayo Clinic Jacksonville Jacksonville, Fl 322243899 Timing: Fiscal Year 2003; Project Start 11-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Mammographically dense breast tissue has been recognized as a strong risk factor for breast cancer, conferring a 4-6 fold increased risk for those women with the most dense compared with those with the least dense breast tissue. Thus, it identifies a group of women in whom the benefits of chemoprevention, more frequent screening, and/or screening by alternative methods may outweigh the associated risks and expense. However, the biological basis of the increased risk for breast cancer in women with mammographically dense breast is unknown. Knowledge of the underlying mechanism will inform more rational prevention strategies. The goal of the proposed research is to better characterize the biological basis for and prognostic importance of mammographic density as a risk factor for development of invasive breast cancer. Specifically, we will explore the relationship of mammographic density with histologic findings on breast biopsy and with serum insulin-like growth factor-1 (IGF-1) bioavailability. This study will be carried out by performing quantitative assessment of mammographic density and measuring IGF-1 and insulin-like growth factor binding protein-3 in 550 women who are undergoing breast biopsy due to mammographic and/or physical examination abnormalities and participating in an ongoing biomarker discovery study, for which Dr. Edith A. Perez (mentor) is the principal investigator and Dr. Betty A. Mincey (candidate) is a co-investigator. The purpose of this ongoing study is to identify and validate potential serum markers for the presence of breast cancer, using proteomic and genomic techniques. The study proposed herein capitalizes on the opportunity provided by this ongoing biomarker trial and will provide a foundation for future research into the relationship of mammographic density, histological diagnoses, IGF-1 bioavailability, and new predictive biomarkers for breast cancer. The candidate, Dr. Betty A. Mincey, is an internist who has developed expertise in the area of cancer prevention, with special interest in assessment and
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management of women at high risk for breast cancer. Dr. Mincey's clinical practice is centered in the Breast Clinic at Mayo Clinic in Jacksonville, Florida. She has worked closely with her mentorship team to develop a career development plan that, along with the work outlined in this research proposal, will enable her to develop into an independent clinical investigator in the field of breast cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MARKERS OF CLINICAL RESPONSE TO PACLITAXEL THERAPY Principal Investigator & Institution: Pietenpol, Jennifer A.; Professor of Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 07-AUG-2003; Project End 31-MAY-2008 Summary: A commonly used approach to the management of locally advanced breast cancer involves the sequential use of chemotherapy, surgery, followed by radiation and adjuvant chemotherapy. With the advent of paclitaxel, there is increasing interest in the use of the drug in the neoadjuvant setting. Our preliminary data show that treatment of xenograft tumors in mice with paclitaxel leads to cell cycle arrest in M-phase that is accompanied by phosphorylation of Bcl-2 and other mitotic epitopes. Further, in the majority of epithelial tumor cells lines examined, the paclitaxel-induced mitotic arrest is transient and cells can exit from mitosis with a 4N DNA content. If the paclitaxelexposed tumor cells are deficient in G1/S checkpoint response, in particular the cyclindependent kinase inhibitory activity of p2lcip1/wafl (p21), we have shown that they can inappropriately enter S-phase with a 4N DNA content. Our laboratory and others have demonstrated that these biochemical events are associated with decreased proliferation and increased apoptosis in the presence of paclitaxel. Thus, these biochemical events may serve as molecular markers of paclitaxel chemoresponsiveness in human tumors. We hypothesize that those patients with locally advanced breast cancer who show the greatest degree of M-phase arrest, Bcl-2 and Cdc25C phosphorylation, and low or absent p21 protein after paclitaxel treatment will be the ones who have the highest rate of complete pathologic response. Moreover, we postulate that we can find additional predictive markers of paclitaxel response by examining protein profiles of pre- and post-paclitaxel exposed tissue using the power of mass spectrometry. In sum, we hypothesize that patients with tumors that show the greatest degree of change in select molecular markers and overall protein expression patterns from pre- to post-paclitaxel treatment, will be those that go on to a complete pathologic response. These interrelated hypotheses will be tested through the following specific aims: Specific Aim 1: To predict the degree of tumor response from paclitaxelmediated changes in markers of cell cycle position, proliferation, and apoptosis that result from paclitaxel administration in patients with locally advanced breast cancer. Specific Aim 2: To predict the degree of tumor response from paclitaxel-mediated changes in p21 protein level and/or phosphorylation in patients with locally advanced breast cancer. We will (a) determine if p21 levels or phosphorylation increase after paclitaxel administration in patients with locally advanced breast cancer and (b) evaluate upstream signaling pathways required for p21 increase and phosphorylation after paclitaxel administration in breast epithelial cells. Specific Aim 3: To evaluate protein expression profiles by mass spectrometry (MS) in biopsy material collected preand postpaclitaxel treatment. We predict that patients with pathologic complete response will demonstrate a greater change in protein expression patterns than patients without pathologic complete response. We postulate that there is a molecular profile that can be identified from biopsies collected pre- and postpaclitaxel treatment that will predict which patients will show the greatest degree of response to paclitaxel as
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measured by the degree of pathologic response at time of definitive surgery. Further, we will gain significant insight to alternative mechanisms of paclitaxel anti-tumor activity and resistance through our mass spectrometry-based analyses of protein profiles from pre- and post-paclitaxel biopsy material. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEASUREMENT OF HYPOXIA IN NON SMALL CELL LUNG CARCINOMA Principal Investigator & Institution: Kelley, Michael J.; Associate Professor of Medicine; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Tumor hypoxia has been implicated as a prognostic marker in human tumors and may be a determinant of tumor response to both radiation and cytotoxic therapy. We propose a pilot phase II clinical trial to determine the safety and feasibility of measurement of tumor hypoxia in patients with non-small cell lung cancer (NSCLC) using the 2-nitroimidazole, EF5. Specific Aim 1: Measurement of hypoxia in NSCLC by EF5 binding. Patients with Stage I/II or Stage III will be administered EF5 prior to surgical biopsy or excision of tumor. Tumor samples will be examined for binding of EF5 to hypoxic areas. Tumor response will be ascertained for those patients with Stage III disease receiving chemotherapy/radiation. Tumor samples will be obtained from patients undergoing repeat tumor biopsy to assess longevity of EF5 adducts. Hypothesis: There is a range of tumor hypoxia in NSCLC that can be detected by EF5 binding. Specific Aim 2: Correlation of hypoxia measured by EF5 with biological markers of hypoxia. Hypoxia induces a number of biological responses mediated through HIF-1-controlled expression. Concurrent measurement of potential serum markers of hypoxia, tissue protein markers of hypoxia, tumor angiogenesis, and apoptosis will be performed to allow correlation with measurement of tumor hypoxia. Hypothesis: Hypoxia measured by EF5 binding in tumor tissues is correlated with biological markers of hypoxia in tumor and blood of patients with NSCLC. Specific Aim 3: Correlate tumor perfusion as measured by clinically applicable methods with hypoxia in patients with non-small cell lung cancer. Tumor hypoxia results from altered tumor blood flow. Advances in imaging techniques allows the non-invasive measurement of tumor blood flow in patients. We will use 150-water PET scanning to measure tumor blood flow and correlate these measurements with tumor hypoxia and each other. Hypothesis: Altered (reduced) tumor blood flow is associated with greater tumor hypoxia. We believe the data from this pilot study will be useful to design future study(ies) with clinical endpoints and to guide selection of subjects for novel hypoxiadirected therapies in patients with NSCLC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MICROCIRCULATION OF UVEAL MELANOMA Principal Investigator & Institution: Folberg, Robert; Fc Blodi Professor; Pathology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 31-MAR-2003 Summary: Ciliary body and choroidal melanomas are among the few forms of cancer treated before a pathologist assigns a grade to indicate if tumor is likely to follow a benign or aggressive course. The metastatic potential of a ciliary body or choroidal melanoma can be assessed by a pathologist most accurately only after the eye has been removed. Unfortunately, when choosing between enucleation and vision-sparing
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treatments for these potentially blinding and lethal tumors, ophthalmologists cannot perform conventional biopsies because of the risk to vision, and fine-needle aspiration biopsy does not provide information about the tumor characteristic most strongly associated with metastasis: the architecture of the tumor microcirculation. The longrange objective is to test and refine noninvasive pretreatment strategies that differentiate between patients whose ciliary body and choroidal melanomas are at low versus high risk for metastasis. These strategies are based on (1) the clinical finding that preenucleation ultrasound spectrum analysis parameters are strongly associated with histologic microcirculatory patterns and extravascular patterns identified after enucleation and (2) the basic finding that deposits of Type VI collagen and its ligand, hyaluronan, contribute to both vascular and extravascular patterns. Additionally, expression of Type VI collagen and hyaluronan in tumors is associated with properties of invasion and metastasis independent of angiogenesis. The first specific aim tests the hypothesis that extravascular tissue patterns formed by Type VI collagen and hyaluronan, also differentiate histologically between patients at low and high risk for metastasis. The second specific aim tests the hypothesis that clinical ultrasound spectrum analysis reliably classifies choroidal and ciliary body melanomas into their histologic risk groups. It is a prospective clinical study of the diagnostic efficacy of ultrasound spectrum analysis in 100 patients who are scheduled for enucleation for ciliary body or choroidal melanoma. The investigators expect to show that ultrasonographic criteria based on power image spectrum parameters can provide a noninvasive substitute for biopsy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALGESIA
MIDCAREER
DEVELOPMENT
IN
NONPHARMACOLOGIC
Principal Investigator & Institution: Lang, Elvira V.; Associate Professor of Radiology and Med; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Alternative medical methods enjoy broad acceptance by the public, but are rarely integrated into conventional medical practice. In the largest prospective randomized study of its kind, published by the Lancet, the candidate showed that nonpharmacologic analgesia in the form of self- hypnotic relaxation during invasive medical procedures significantly reduces patients' pain anxiety, drug use, number of complications, hemodynamic instability, and procedure time. This results in substantial resource savings. The immediate goal of the candidate is to expand and validate this concept of integrated alternative/conventional health care delivery across disciplines. The long-term goal is the successful transition from scientific investigation to general implementation of acute non-pharmacologic analgesia in clinical settings. The candidate is uniquely situated to achieve the state goals: A strong foundation in laboratory and clinical research as well as her position as Director of International Radiology provides her the necessary credibility to promote and implement mind body intervention during invasive medical procedures. Her acceptance by both conventional medical and mindbody oriented professional societies permit integration of her methods into both communities. The candidate's RO1 and DOD funding focuses on assessment on nonpharmacologic analgesia during invasive vascular procedures and during large core breast biopsy. Under the proposed mid-career award, she will (1) acquire authoritative expertise in the introduction and quality assessment of non- pharmacologic analgesia techniques in conventional clinical settings (2) assume a key role in the newly established Harvard-wide Division for Research and Education and Complementary
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and Integrative Medical Therapies, and (3) mentor the next generation of researchers and practitioners in this field. Towards these aims the candidate will acquire additional research skills in educational technology, quality assessment, and web-based dissemination; acquire expertise in additional complementary and alternative therapies; and will make available to other researchers data banks, ideas, experience and patients in fully monitored clinical environment. She will assume primary mentoring responsibility for a total of 15 beginning clinical researchers. Upon completion, the candidate will have established herself as an authority in the introduction and quality assessment of combined alternative/conventional medical practices. The mentoring of beginning clinical researchers will have contributed towards fostering a self- sustaining mode of integrated practice in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR CLASSIFICATION OF OSTEOSARCOMA Principal Investigator & Institution: Lau, Ching; Associate Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Applicant's Description) Osteosarcoma is the most common malignant bone tumor in children. Approximately 80 percent of patients present with non-metastatic disease. After the diagnosis is made by a biopsy, treatment involves 3-4 courses of neoadjuvant chemotherapy before definitive surgery, followed by post-operative chemotherapy. With currently available treatment, approximately 30-40 percent of patients with non-metastatic disease relapse after therapy. There is no prognostic factor that can be used at the time of diagnosis to predict which patients will have a high risk of relapse. The only significant prognostic factor predicting the outcome in a patient with non-metastatic osteosarcoma is the histopathologic response of the primary tumor resected at the time of definitive surgery. The degree of necrosis in the primary tumor is a reflection of the tumor response to neoadjuvant chemotherapy. Higher degree of necrosis is associated with lower risk of relapse and therefore better outcome. Patients with lower degree of necrosis have a much higher risk of relapse and poor outcome even after complete resection of the primary tumor. Unfortunately this poor outcome cannot be altered despite modification of post-operative chemotherapy to account for the resistance of the primary tumor to neoadjuvant chemotherapy. Thus there is an urgent need to identify prognostic factors that can be used at the time of diagnosis to recognize the subtypes of osteosarcomas patients that have high risk of relapse so that more appropriate chemotherapy can be used at the outset to improve the outcome. We propose to establish a molecular classification system to distinguish such subsets of osteosarcoma based on their gene expression profiles. This project will be a collaboration among several institutions including the Texas Children's Cancer Center, Baylor College of Medicine, Pediatric Oncology Branch, NCI, Cancer Genetics Branch, NHGRI, Biometric Research Branch, NCI and Incyte Pharmaceuticals, Inc. We plan to recruit 100 osteosarcoma patients who are receiving the same therapy through a treatment protocol. Using cDNA microarrays, we will investigate the gene expression profiles of the tumor tissues at the time of biopsy and definitive surgery. These profiles will be correlated with clinical outcome. In addition, we also plan to compare the gene expression profiles of the primary tumor and those of the metastatic lesions. The specific aims are: 1. To validate and optimize cDNA microarray technology for gene expression profiling of clinical specimens. 2. To establish the relevant gene expression profiles for molecular classification of osteosarcoma by correlating these profiles with clinical outcome, chemosensitivity, and metastatic potential.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR DETECTION OF PROSTATE CANCER IN URINE Principal Investigator & Institution: Cairns, Paul; Fox Chase Cancer Center Philadelphia, Pa 191112434 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 31-MAY2006@@$Abstract: Description (provided by applicant): Novel approaches for the early detection and management of prostate cancer are urgently needed. Adult sporadic cancers are known to arise through the accumulation of multiple clonal genetic alterations which can be used as targets for the detection of neoplastic cells in bodily fluids that surround or drain from an organ. Since the prostate is a gateway organ for urine passing from the bladder to urethra, we hypothesized that prostate cancer DNA might be present in urine. Using the sensitive methylation specific PCR we have established that a new molecular target, GSTP1 gene hypermethylation which is well established as "early", frequent and cancer specific can be detected in a simple voided urine from patients with curable prostate cancer. We have demonstrated for the first time that molecular detection of prostate cancer in urine is feasible. Our specific objectives are; to determine the diagnostic utility of hypermethylation-based detection in urine from two clinically problematic populations, men with a persistently elevated PSA and negative biopsy and high risk men with a normal PSA, and to validate our initial findings of high specificity through a comprehensive approach to negative controls leading to the useful application of gene hypermethylation in prostate cancer diagnosis and management. Our long range goal is to make these molecular detection tests a clinical reality. We have preliminary evidence which indicates that a sensitive and specific molecular test providing diagnosis of prostate cancer is feasible from a simple urine specimen. We will test this further in two clinically problematic populations in need of better diagnosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR EPIDEMIOLOGY OF PROLIFERATIVE BREAST DISEASE Principal Investigator & Institution: Dupont, William D.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 07-AUG-2003; Project End 31-MAY-2008 Summary: We will study molecular and histologic markers of breast cancer risk in women with benign proliferative breast disease. Specific markers to be evaluated include the T29 to C polymorphism of the TGF-beta1 gene, the type I and II receptors for the TGF-beta cytokines, the phosphorylated Smad2 intracellular signaling molecule, and the ErbB-1 and ErbB-3 receptors of the epidermal growth factor receptor family. We will also study the effect of epithelial hyperplasia lacking atypia on breast cancer risk among African-Americans. We are currently conducting a large retrospective cohort study of women who underwent benign breast biopsy. Paraffin embedded tissue from the entry biopsy of these patients is available. By the end of this project we project that we will have observed 781 breast cancer cases during follow-up among 16,846 study subjects in this cohort. We will expand this cohort to include women from Metro General/Hubbard Hospital in order to increase the number of African-American women available for study. We will conduct a series of nested case-control studies on these women. Women who develop breast cancer on follow-up will be the case patients in these studies. Two controls will be selected for each case matched on age and year of biopsy. PCR and immunohistochemical methods will be used to study gene polymorphisms and
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abnormal protein expression, respectively. Conditional logistic regression analysis will be used to assess the individual and combined effects of molecular, histologic and epidemiologic variables on breast cancer risk. This project will permit the combination of modern methods in molecular biology, pathology and epidemiology to assess potentially powerful new markers of breast cancer prognosis, and may lead to important advances in the prevention and treatment of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MR BRACHYTHERAPY
GUIDED
PROSTATE
CANCER
DIAGNOSIS
AND
Principal Investigator & Institution: Tempany, Clare M.; Director of Clinical Mri; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-JUN-2001; Project End 31-MAY-2004 Summary: (Applicant's Description) Prostate cancer represents one of the most significant challenges in medicine and public health. Its increased diagnosis has lead to a virtual epidemic. A growing number of men are choosing to minimize the post treatment side effects. The goal of image-guided treatment is to control the surrounding structures. In the proposed research we plan to apply an interactive MR image-g treatment of localized prostate cancer. We have developed an MR-guided brachytherapy program system. MRI is uniquely suited to imaging the prostate allowing excellent visualization of the, tumor and adjacent tissues. Since this program was introduced there have been significant localization, navigation and delivery of therapy, now used in neurosurgery. We propose to adapt diagnosis and treatment of prostate cancer. The challenge is to increase the information content of intraoperative image data by using multimodal features as well as preserving the interactivity and the 3D real time imaging precise delivery of treatment to maximize tumor control will be achieved and will improve treatment. We will (1) Perform MRI-guided prostate biopsies. The diagnosis and localization of prostate cancer maybe improved by using MRI guidance. We will enroll men suspected of having prostate cancer, for biopsy (n=91); (2) Implement and evaluate a fully integrated delivery system. This system will allow preoperative and intraoperative MR images of the prostate to be available on-line in the operating room. There will be image segmentation and registration methods available which will allow us to use the entire accessible image dataset for MRI-guided Brachytherapy. We will randomize 108 men to treatment with or without the new methods. The results will be compared with two retrospective studies using US and basic MR as guidance. We will develop an MR and CT quality assurance program, (n=80, from the brachytherapy cohort). The overall clinical enrollment will take up to 2 years. Ultimately, our long-term goal is to extend the use of these image guidance modalities (e.g. US) and be adapted for guidance of novel cancer treatments such as the local injection of gene therapy or focal laser or cryoablation. In keeping with our longterm goals and those of the RFA we will conduct this work in collaboration with two industrial partners, namely Daum and Alphatech for the biopsy program and the translation of our techniques to US-guided brachytherapy systems. An ultimate goal beyond the scope of this application is our collaboration with General Electric Medical systems (GEMS) on new MR-guided technical advances and an NSF funded project to develop medical robotics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MR STUDIES OF MYOCARDIAL CREATINE KINASE METABOLISM Principal Investigator & Institution: Bottomley, Paul A.; Russell H. Morgan Professor; Radiology and Radiological Sci; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-MAY-1997; Project End 31-MAR-2008 Summary: (provided by applicant): Oxidative energy metabolism is essential for normal cardiac contractile function. Magnetic resonance spectroscopy (MRS) with phosphorus (31P) is uniquely able to noninvasively assess key metabolites, adenosine triphosphate (ATP) and phosphocreatine (PCr), in the heart. Patient MRS studies show reduced PCr and ATP: levels in myocardial infarction (MI). Human biopsy and autopsy data show that total myocardial creatine (CR=PCr+unphosphorylated creatine,Cr) is also reduced, while animal studies show that the rate of generating ATP from PCr via the creatine kinase reaction (CKR) is reduced in dysfunctional myocardium post-MI. These data together demonstrate that CKR metabolite levels and energy supply are compromised in these common disease states. Prior to the first funding period of this grant, studies of myocardial CR were possible only with invasive tissue biopsies. In the first funding period, we developed noninvasive water-referenced localized MRS using protons (1H) to quantify myocardial CR. We showed, for the first time, the noninvasive detection and quantification of CR in canine and human myocardium, and CR depletion in non-viable, infarcted tissue in patients with MI. Due to the higher 1H MRS sensitivity and much greater proton concentration of the CR moiety, CR MRS can provide a more than 20-fold gain in sensitivity relative to 31P studies of PCr. Therefore, in this competitive renewal, we plan first to advance quantitative 1H MRS of CR by reducing its motion sensitivity with constructive averaging techniques, and introduce CR imaging methods to reveal metabolic defects in patients with MI and delayed hyper-enhancing 1H MRI lesions. Second, we will extend this work by combining CR imaging with contrast-MRI to assess the metabolic viability of hyper-enhancing MRI lesions in acute MI and chronic followup. This will address the clinically-relevant question for contrast MRI, of whether such lesions initially include substantial amounts of metabolically viable tissue. Third, we have developed and tested a new fast 31P MRS method that provides CKR flux measures in scan times that are tolerable by patients. For the first time, we will discover the rate at which ATP energy is supplied via the CKR in human heart. We will apply this method to learn whether the CKR ATP supply increases to meet energy demand during stress, and whether it is altered in MI patients with dysfunction, and thereby provide new, fundamental information about myocardial energetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTI IMAGER COMPATIBLE ROBOT FOR PROSTATE ACCESS Principal Investigator & Institution: Stoianovici, Dan; Urology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The research objective in this R2l and R33 phased application is to advance the technology utilized in the diagnosis and delivery of localized therapy in the treatment of prostate cancer through the development of instrumentation allowing for improved and reproducible navigation and controlled probe insertion into the prostate gland. The deliverable is an accurate mechanism for performing precise image-guided procedures such as biopsy, brachytherapy, cryosurgery, hyperthermia, interstitial laser therapy, focused ultrasound and microwaves, chemotherapy, gene therapy, or other novel procedures. We propose the
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development of a new instrument for precise image-guided intervention. Even though this proposal's application relies in the urologic field, the proposed system applies to a large variety of other specialties. This application restricts the application range to the diagnostic and treatment of the prostate since urologic applications are our main domain of interest. The centerpiece of research is a compact image-guided robotic system which can be used with standard and modern medical imaging equipment. The novelty of the system relies in its compatibility with multiple imaging modalities, such as fluoroscopy, ultrasound, computer tomography (CT), magnetic resonance imaging (MR), and spectroscopic imaging (MRSI). This allows not only for performing procedures with the imager of choice but also for using cross-platform, combined imaging modalities. An intense research effort is presently focused on the development of novel methods for advanced imaging and improved visualization. In contrast, the instrumentation used for image guided navigation and therapy delivery advanced modestly. Needle procedures are typically performed freehand or with a "template" device under transrectal ultrasound guidance. At present, no mechanical device exists for controllably and repeatedly access the prostate with a precision comparable with that of modern medical imaging systems. While the medical community is still divided about the best treatment modality of prostate cancer, there is undivided agreement about the poor specificity and predictability of the currently used prostate access techniques. Enhanced MR imagery provides uncontested tissue contrast and image quality, which ought to be used for guiding biopsy and localized therapy. This goal requires miniature, extremely high dexterity robots that are able to operate inside the magnet of MR scanners, which may be "open" or conventional closed bore systems. This task also demands a quantum leap in the current technology of mechatronic devices and clearly leads medical robotics into the next millennium. We propose to develop an instrument that could exploit the most advanced imaging methods for implementing the results obtained by urologists, oncologists, radiologists, radiotherapists, and biomedical researchers into clinical use. It creates means for measuring the local extent of the disease, for performing controlled biopsy and therapy delivery through advanced image-guided navigation and control. In conjunction with the recent citrate/choline ratio methods of tumor localization under MRSI, for example, this multi-application system could be used to perform precise tumor-centered biopsy procedures. The main research challenge relies in the robot compatibility with multiple imaging systems, especially the conventional MR imager. Innovative engineering research will address design miniaturization, adequate material selection and manufacturing. The mechanical part, which will operate within the conformed space of the imager in close proximity of the prostate, will be radiolucent, nonmagnetic, dielectric, and will provide means for safety and sterilization. For this, the system, including the motors, will be constructed of materials such as plastics, carbon fiber composites, ceramics, glasses, and rubbers. The use of electricity in the imager's room will be eliminated by using optical sensors and pneumatic/hydraulic motors while all control equipment will be located in the control room of the imager. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTI-SLICE PERFUSION MR IMAGING OF THE HUMAN KIDNEY Principal Investigator & Institution: Gach, H Michael.; Radiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Kidney transplantation is the most cost-effective therapy for end-stage renal disease. However, acute rejection (AR), delayed graft
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function (DGF) and immunosuppressive drug nephrotoxicity remain common complications. It is important to distinguish AR from DGF and immunosuppressive drug toxicity, since the therapeutic options for each may differ significantly. Bioassays of serum creatinine, blood urea nitrogen (BUN), and urine output may indicate the occurrence of renal dysfunction but not the type. Biopsy remains the gold standard, but is invasive and highly localized. Renal perfusion can be a sensitive and distinguishing parameter of the rejection process. AR is characterized by a marked, sudden decrease in both perfusion and function of the kidney while DGF and immunosuppressive drug toxicity typically show normal or slightly reduced perfusion in qualitative MRI studies. Perfusion MRI can identify spatial and temporal perfusion changes in the kidney that will aid in the diagnosis of AR. The specific aims of our research are: 1) to develop and improve non-invasive multi-slice ASL perfusion MRI using simultaneous proximal and distal irradiation (SPDI) and 2) to use SPDI to measure perfusion rates in healthy and transplant volunteers. SPDI labels endogenous arterial water using a variant of continuous arterial spin labeling (CASL). MR images will be acquired with ultra-fast snapshot techniques (e.g., EPI). The research is designed to test the sensitivity and reliability of SPDI for detecting regional perfusion variations, and compare SPDI with quantitative multi-slice dynamic susceptibility contrast (DSC) measurements. The perfusion MRI technique will be tested in healthy and transplanted kidneys twice during the first three months following transplantation. The condition of the transplanted kidneys will be categorized (e.g., normal, AR, and DGF) based on bioassay and biopsy results. The study will test the hypotheses that 1) multi-slice MRI using SPDI can reliably and accurately measure renal cortical perfusion rates in humans with a systematic error of less than 0.6 ml/g-rain, and 2) changes in renal cortical perfusion rates of greater than 1 ml/g-min in the period within 3 months after transplantation can be used in association with MR angiographic, biochemical, and biopsy data to distinguish AR from DGF and immunosuppressive drug toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NATURAL HISTORY OF ANAL NEOPLASIA IN HIV INFECTED MEN Principal Investigator & Institution: Palefsky, Joel M.; Professor of Medicine; Stomatology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 25-SEP-1991; Project End 31-JUL-2004 Summary: (adapted from the Abstract): This is a re-submission of a competing renewal application for continuing support of a grant entitled "Natural History of Anal Neoplasia in HIV-infected Men" (R01 CA54053). Data from the first five years of the study show a high baseline prevalence of anal disease among HIV-positive men and a very high incidence of anal squamous intra-epithelial lesions (ASIL), including highgrade squamous intra-epithelial lesions (HSIL). With the recent advent of "highly active and retroviral therapy" (HAART), which includes protease inhibitors, possibly HIVpositive individuals will live longer, and may show a shift in the HIV epidemic from morbidity and mortality from opportunistic infections to those of more chronic diseases with a slow natural history, such as cancer. Because anal HSIL likely represents the precursor lesion to invasive anal cancer, and progression to cancer may take a number of years, the increased longevity of HIV-positive individuals due to HAART may, therefore, increase their risk of anal cancer. This is especially of concern given the preliminary data which suggest that the improved immune function associated with HAART does not lead to anal disease regression among men with ASIL before they
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began HAART. Thus, with the use of HAART a substantial number of HIV-positive men may be at risk of invasive anal cancer. In this renewal, the Investigator has three specific aims: (1) to study the natural history of ASIL and anal human papilloma virus (HPV) infection among patients on HAART; (2) to compare the natural history of ASIL and anal HPV infection to those not on HAART; and (3) to continue follow-up of the HIVpatients to define more fully the natural history of ASIL and anal HPV infection in these men. To reconstitute their cohort, this research group will recruit 350 new HIV-positive patients without HSIL and will continue to follow their existing HIV-positive and HIVnegative patients. The researchers will examine the men at 6-month intervals with an interview, an anal examination including cytology, HPV testing, and anoscopy with biopsy of visible disease. Blood will be obtained from HIV-positive patients for CD4/CD8 counts and HIV viral load at each visit. In all patients, additional anal examinations will be performed at 3-month intervals if anal disease is detected on cytology or histology. All patients diagnosed with HSIL will be referred for therapy. Similar to cervical cancer but unlike other malignancies related to HIV, invasive anal cancer is most likely a preventable disease. Because a large proportion of HIV-positive individuals will soon be on HAART, an understanding of the effect of these drugs on the natural history of anal disease and anal HPV infection will be essential in order to design a screening program for high risk individuals as well as better treatment and prevention efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NATURAL HISTORY OF CIN2 IN ADOLESCENTS Principal Investigator & Institution: Moscicki, Anna-Barbara; Professor; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: This is a 5 year prospective study designed to: 1) examine the natural history of CIN-2 (cervical intra-epithelial lesions) subset of high grade squamous intra-epithelial lesions (HSIL) among adolescents, and 2) identify immunologic and behavioral factors associated with regression of CIN 2 lesions. The study of immunologic and behavioral factors that may influence CIN 2 regression will include: sustained local (cervical) Th-1 like cytokine response, systemic cytotoxic T lymphocyte (CTL) responses to HPV (for HPV 16 positive women only), size of lesion at diagnosis, amount of cervical immaturity (ectopy) at diagnosis, and hormonal contraception. Other factors that will be monitored for possible effects include high risk sexual behavior and outcomes (multiple partners, substance use, pregnancy, sexually transmitted infections, and bacterial vaginosis). Last, this study proposes to compare local immunologic responses among women who at baseline visit are diagnosed with CIN-1, CIN-2 and normal histology on biopsy. Approximately 40,000 young women 19 years or younger are expected to undergo cervical cytology screening within the Northern California Kaiser Permanente clinics over a 24 month period. Adolescents aged 13-19 years with abnormal cytology (estimated N=2680) will be recruited. Baseline examination will include interview and cervical samples for HPV DNA testing and quantitative cytokine studies using reverse transcriptase polymerase chain reaction techniques. Colpophotographs will be obtained to determine lesion size. All samples will be obtained prior to biopsy. Those with biopsy-confirmed CIN 2 (N=416) will be followed every 3 months using interview, colposcopy, HPV DNA testing, and cytology and undergo immune studies (cervical cell cytokine analysis using real-time RT-PCR and peripheral blood CTL assays on women with HPV 16 infection) until the end of the study. Women with CIN-3 are exited for standard therapy. Those with biopsied confirmed low grade (L) SIL or less will exited.
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Understanding of the natural history of CIN 2 will be critical in efforts to construct costeffective strategies for cancer screening in adolescents. In addition, defining immunologic factors associated with CIN 2 regression will have important implications for vaccine and therapeutic strategies and defining clinical (including repeated HPV DNA testing) and behavioral risks will have important implications for triage and counseling strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NYU COOPERATIVE PROSTATE CANCER TISSUE RESOURCE Principal Investigator & Institution: Melamed, Jonathan; Pathology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 24-MAY-2000; Project End 31-MAR-2005 Summary: This is a proposal to establish a Cooperative Prostate Cancer Resource at the NYU School of Medicine in the context of a national Cooperative Prostate Cancer Tissue Resource Netwerk. The application combines resources and patient material/information from four major New York City sites (Tisch Hospital-NYU School of Medicine; Bellevue Hospital [public], New York Harbor VA Medical Center, and NYU Downtown Hospital). The proposal builds on the following existing strengths: Large volume of radical prostatectomy specimens (greater than 500/year); a large repository of archival paraffin blocks of radical prostatectomy cases (greater than 2,500) and prostate biopsy cases (greater than 4,000) going back to 1991; access to greater than 660 prostate biopsy cases annually; existing active prostate cancer frozen prostate tissue bank; existing limited clinical database of radical prostatectomy cases; existing bank of genomic DNA samples from radical prostatectomy patients; follow-up and demographic data for patients with prostate cancer; experience and resources for development and maintenance of a breast cancer tissue bank and relational clinicopathological database; and with procurement of fresh, frozen, and fixed tissue from a variety of neoplastic and normal human tissues. The Specific Aims of this proposal are: (1) To establish retrospective and prospective prostate cancer paraffin block repositories a repository of microarray tissue blocks of prostate cancer; (2) To establish a prostate cancer frozen tissue repository and a repository of frozen minimicroarray blocks; (3) To establish retrospective and prospective prostate biopsy repositories; (4) To establish retrospective and prospective metastatic prostate cancer tissue repositories; (5) To establish a bank of frozen and fixed normal prostate tissue; (6) To establish a fresh prostate cancer tissue procurement service; (7) To contribute to the development of a clinical-pathological database containing demographic and pertinent clinical and outcome information; (8) To establish a repository of genomic DNA and serum for the analysis of genetic and soluble tumor markers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OLFACTORY NEURONS FROM BIPOLAR PATIENTS Principal Investigator & Institution: Hahn, Chang-Gyu G.; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 23-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant) This proposal seeks a structured research training program, which will enable Chang-Gyu Hahn. M.D. Ph.D. to become an independent investigator as he demonstrates the utility of olfactory receptor neurons (ORNs) to examine the neurobiology underlying bipolar disorder. Career Goals and Objectives: With the career goat of being able to apply the most advanced molecular techniques to
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clinically relevant research paradigms through the ORN system, he proposes a career development plan focusing on following areas. 1) ionic imaging and the neurobiology of the human ORN system and 2) Single cell antisense RNA amplification technique. Career Development Activities: The candidate will receive specialized training in ionic imaging in human olfactory neurons (guided by Nancy Rawson, PILD, co-mentor) and in single cell molecular technique (supervised by James Eberwine, Ph.D., co-mentor). Dr. Karl Rickels will provide individual supervision for the treatment outcome study component of the specific aim 2. Dr. Robert H. Lenox will oversee the career development program through integrating formal courses, lab meetings and supervisions. Background: ORNs, the only CNS neurons that are obtainable through olfactory epithelial biopsy, provide a unique opportunity to investigate molecular events in neurons from living subjects. By obtaining ORNs during specific stages of the illness, in conjunction with a longitudinal follow-up of patients, pathophysiologic significance of molecular events in neurons can be linked to bipolar disorder. Hypothesis: Our preliminary data suggest that intracellular calcium responses to odbrants are altered in bipolar disorder. I) Intracellular calcium responses of ORNs to odorants are predominantly a decrease as a trait of bipolar disorder. 2) The decreased ICa responses in ORNs from bipolar patients are due to altered expression of the genes that are involved in calcium flux. 3) The percentage of ORNs that respond to odorant stimulation is overall decreased following lithium treatment. 4) ORNs in explant cultures from bipolar patients will show similar ICa responses as in vivo ORNs of patients. Specific Aims: 1) To characterize trait- and mood state- dependent alterations in ICa homeostasis and gene regulation in ORNs from bipolar patients. 2) To identify therapeutically relevant changes in ICa homeostasis following lithium treatment. 3) To characterize ORN cultures from bipolar patients using odorant induced ICa responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPIOID RECEPTORS AND LIGANDS: NOVEL MARKERS FOR CANCER Principal Investigator & Institution: Lever, John R.; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (Revised Abstract) (provided by applicant): Opioid receptors are overexpressed by a variety of human and animal tumors. Markers for in vivo characterization of tumors expressing opioid receptors may have value as diagnostic aids, and would present opportunities for novel studies of the roles played by opioids in neoplasia. Little attention has focused on this arena despite the fact that opioid receptor antagonists are in clinical trials as antitumor agents, and widely prescribed opioid receptor agonists, such as morphine, may be tumor promoters. Our goal is to develop and validate imaging radioligands and mouse tumor models for in vivo studies of opioid receptors on breast and lung cancers in order to provide a foundation for future imaging studies of opioid receptor involvement in human cancers. Our emphasis will be upon radioligands labeled with 1-123, Tc-99m and In-111 for SPECT / microSPECT scanning. Further, we plan to determine the frequency and extent of expression of opioid receptors in human breast cancers by in vitro screening of biopsy samples and associated normal breast tissues, and to ascertain correlations of opioid receptor expression with a limited panel of tumor markers, including steroid hormone receptors. Specifically, we propose: (1) to design, synthesize and chemically characterize novel opioid receptor ligands labeled with SPECT imaging radionuclides; (2) to determine radioligand affinity, selectivity and specificity for opioid receptor types in vitro; (3) to
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characterize in vivo radioligand binding to opioid receptors in normal and tumor bearing rodents; (4) to evaluate radioligand pharmacokinetics and pharmacology in mice by microSPECT, and to use microSPECT and microCT imaging to investigate the effects of opioid receptor agonists and antagonists on MCF-7 mammary tumor xenograft growth in nude mice; and (5) to establish the frequency and extent of opioid receptor expression in human breast cancer biopsy specimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: P53 AND DNA PLOIDY IN BARRETT'S METAPLASIA Principal Investigator & Institution: Younes, Mamoun; Associate Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 09-JAN-2001; Project End 31-DEC-2005 Summary: The goal of this study is to determinewhether the accuracy and costeffectiveness of endoscopic surveillance protocols aimed at detecting early malignant transformation in patients with Barrett's metaplasia (BM) can be improved by: 1) testing the hypothesis that p53 protein accumulation, DNA aneuploidy, and increased G0G1 or G2M fractions are more accurate and objective markers of malignant potential in Barrett's metaplasia (Barrett's esophagus) than the routine morphologic evaluation of dysplasia, 2) determining whether biopsy and cytology combined are more useful than either biopsy or cytology alone, 3) determining the time period that elapses between the appearance of LGD/IND, p53 protein accumulation, and DNA ploidy abnormalities, and between the development of high grade dysplasia (HGD) and adenocarcinoma (CA), and 4) perform cost-analysis to determine whether a surveillance program can be constructed in which biopsy and cytology are utilized in conjunction with p53 and DNA ploidy determination, and is less costly than current surveillance programs. Evaluation of p53 accumulation and DNA ploidy studies will be performed on initial and follow-up biopsies and brush cytology material from at least 200 patients with Barrett's metaplasia (BM). Step sections of biopsies (Bx) will be stained with hematoxylin and eosin, Feulgen stain for DNA quantitation, and immunostained for p53 protein, p53 gene mutational analysis will be performed by direct sequencing on microdissected tissues. Each case will be then analyzed for dysplasia, DNA ploidy patterns by image analysis, and p53 accumulation and gene mutation. Cytologic preparations (Cy) will be also evaluated for dysplasia, DNA ploidy patterns by image analysis, and p53 accumulation. The data will be compiled every two years and correlated with the patients outcome, using the development of HGD and CA as end points in separate analyses, and evaluated by univariate and multivariate analysis. The sensitivity, specificity, and positive and negative predictive value of each of these markers as predictors of HGD and of CA development will be determined separately on markers detected by Bx, Cy, and by the Bx and Cy combined. These will be compared to determine whether the use of both Bx and Cy in the follow-up of patients with BM is better than Bx or Cy alone. The time between the appearance of one of the markers and the development of carcinoma will also be studied, in order to identify a period of time in which close endoscopic surveillance is both clinically warranted and cost-effective. p53 mutations will be compared with p53 protein accumulation, and with DNA ploidy and patient outcome in order to determine if there are specific mutations associated with progression to DNA aneuploidy and CA. A multi step progression model will be constructed, upon which a new surveillance program will be proposed. A cost analysis will be then performed to determine whether a molecular based surveillance program would be more costeffective than current program which is based on morphologic grading of dysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENIC MECHANISMS OF THE VASCULOPATHY OF JDM Principal Investigator & Institution: Grom, Alexei A.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Despite the fact that juvenile dermatomyositis is viewed "primarily as a systemic vasculopathy rather than simply an inflammation of muscle and skin", our knowledge of the vascular abnormalities in this disease is based on only few descriptive histopathological studies. Such vasculopathy is often associated with the capillary necrosis that eventually leads to capillary loss and tissue ischemia, a phenomenon that is likely to be responsible for muscle infarctions and severe ulcerative complications involving skin and gastro-intestinal tract in about one third of JDM patients. In contrast to normal physiologic response to tissue ischemia, we have not been able to detect up regulation of the expression o f t he major a ngiogenic factors i n the affected JDM muscles. Based on this, we hypothesize that blood vessel repair in JDM is hampered by the blunted angiogenic response normally induced by tissue ischemia. In turn, this may be secondary to the altered balance between angiogenic and angiostatic components of the inflammatory response. Therefore, it is expected that in pretreatment muscle biopsies in children with JDM, there will be histologic and functional evidence of vasculopathy and impaired angiogenesis that will be significantly correlated with the outcome of the disease. In the proposed study, Specific Aim #1 will focus on detailed quantitative morphometric characterization of JDM vascular abnormalities. It will test the hypothesis that quantitative assessment of vasculopathy in pretreatment muscle biopsy may have significant prognostic value. Specific Aim #2 will identify differentially expressed genes in muscle biopsy samples that will distinguish JDM patients with vasculopathy and tissue damage from those with relatively benign disease. The differentially expressed genes will be sought in global gene expression profiles as well as in angiogenesis pathways with focus on the direct acting angiogenic factors and their receptors, as well as inflammatory cytokines and chemokines that can mediate release of the angiogenic factors. Particular attention will be given to the balance between the angiogenic ELR + and the angiostatic ELRchemokines. In our preliminary data, the interferon y induced protein 10 (IP-10), a potent ELR angiostatic chemokine, was highly expressed in all JDM muscle biopsy samples. Specific Aim 3 will focus on gene expression profiles in peripheral blood. The long-term goal of this proposal is to understand the molecular mechanisms underlying vasculopathy and to define potential targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEPTIDE MICROARRAY FOR CANCER CELL SURFACE RECEPTORS Principal Investigator & Institution: Lam, Kit S.; Professor and Chief; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 09-JAN-2001; Project End 31-DEC-2003 Summary: (Applicant's Description) With the invention of hybridoma technology by Kohler and Milstein (1975), numerous monoclonal antibodies (MoAbs) against cell surface antigens or receptors have been developed and used clinically as diagnostic agents. In the last two decades there has been enormous effort in both academia and pharmaceutical industry to develop monoclonal antibodies to treat human cancers. The recent clinical success of Rituxan (anti-CD 20 MoAb against B-cell lymphoma) and Herceptin (anti-Her2/neu MoAb against breast cancer) in the treatment of human
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cancers has validated the cell-surface targeting approach for cancer therapy. Evaluation of biopsy specimens for the presence of CD20 and Her2/neu is now routinely done for non-Hodgkin lymphoma and breast cancer, respectively. Combinatorial chemistry has become one of the most important technologic advances in recent years for basic research and drug discovery. Millions of compounds can be generated and screened for their ability to bind to a specific target macromolecule or to elicit a specific biological response (Lam 1997). In this proposal, we hypothesize that by using the state-of-the-art "one-bead one-compound" combinatorial library method, we can rapidly identify a large number of cell surface binding peptides that are unique to different tumor types. We further hypothesize that with the novel chemical microarray technique that was recently developed in our laboratory, we can rapidly characterize the binding specificities as well as functional effects of the identified peptide ligands on a large number of tumor cell lines. Peptides that are unique to human tumors can then be used to determine the ligand binding profile of human cancer biopsy specimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT STUDY--GENETICS OF DIABETIC NEPHROPATHY IN BABOON Principal Investigator & Institution: Rincon-Choles, Hernan; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Diabetic nephropathy (DN), a microvascular complication of diabetes mellitus (DM), is the main cause of end stage kidney disease worldwide. There is a great need to find animal models of DM and DN that better resemble the physiopathological changes in humans. Both DM and DN are influenced by environmental factors and heredity. The SFBR has approximately 2400 baboons in a pedigreed colony, with a 10 cM linkage map available for 800 of these animals, and additional animals are being currently genotyped. Some baboons in this colony have developed clinical features of type-2 DM and 4 animals biopsied thus far have histological features similar to those found in humans with DN. Preliminary fasting blood glucose (FBG) screening of 478 baboons showed 44% with FBG equal to or > 126 mg/dl. Preliminary screening for microalbuminuria (MA) in 298 animals showed 33.5% of 149 control and 42% of 149 diabetic baboons had MA. One of the control and 3 of the diabetic baboons had proteinuria. A subset of 7 age- and weight- matched female baboons averaging 20 years of age underwent kidney biopsy, 4 diabetics and 3 controls. Diabetic animals had FBG > 126 mg/dl, hemoglobin A1C > 6%, abnormal intravenous glucose tolerance test and normal C-peptide levels. Kidney histology showed that diabetic animals had larger glomeruli, thickened glomerular basement membrane, mesangial matrix expansion and areas of mesangiolysis with early nodule formation. These histological changes closely resemble those of DN in humans, making the type-2 diabetic baboon a useful model of DN. We hypothesize that the characterization of the DN phenotype in genotyped baboons from the pedigree, confirmed by kidney biopsy, will allow us to run a genomewide linkage analysis to identify genes and chromosomal regions associated with the development and progression of DN. We will conduct a population-wide screening in 1000 animals to study the prevalence of DM and the pattern of microalbuminuria in the baboon. The intrarenal renin-angiotensin system (RAS) is activated in DN, as evidenced by the heightened hemodynamic response to blockade of the RAS in human DN. We will characterize the phenotype of DN in a subset of animals and investigate the kidney expression of components of the RAS and other cytokines and matrix proteins associated with DN. We will then perform a genome-wide search to find and localize
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quantitative trait loci that influence variation in albuminuria and disease progression. Our goal is to identify early markers of disease progression amenable to intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POSITRON EMISSION TOMOGRAPHY IN PROSTATE CANCER Principal Investigator & Institution: Miller, Tom R.; Professor; Radiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The primary goal of this project is determination of the value of positron emission tomography employing the radiopharmaceutical C-11 acetate (AC-PET) in patients with medium- and high-risk prostate cancer who are candidates for treatment with curative intent by radical prostatectomy or radiation therapy because the standard clinical and imaging evaluation was negative for tumor spread beyond the prostate. The following specific aims will be pursued: 1. Determine the role of AC-PET in changing initial patient management; 2. Determine the value of AC-PET in predicting recurrence; 3. Assess the performance of AC-PET for detection of lymph nodes by comparison with biopsy. Study Design: The study includes a total of 285 patients in two groups who are scheduled for treatment with curative intent, both of whom will undergo AC-PET imaging prior to treatment. For the surgery group, if the PET examination is negative for disease outside the prostate gland, the treatment will proceed and the patient will be followed for evidence of recurrence. If the PET examination is positive, the referring physician will be encouraged to undertake confirmatory studies, which may lead to a change in therapy. All patients in the radiation therapy group will undergo the standard treatment, and they will then be followed for evidence of recurrence. The lymph node biopsy results in the surgery patients will be correlated with the PET findings to compute the positive and negative predictive values of AC-PET. Anticipated Results: AC-PET will lead to cancellation of radical prostatectomy in at least 10% of the surgical patients. It is also expected that ACPET will significantly improve the prediction of recurrence compared with conventional methods based on clinical stage, PSA and Gleason score. The predictive value of ACPET should be high when correlated with the pathological data. Health Relevance: If this project is successful, it will have a significant impact on the management of patients with moderate- and high-risk prostate cancer who are candidates for curative treatment. In some of these patients, a positive PET scan will lead to cancellation of planned surgery, sparing these men the morbidity of radical surgery while permitting some of them to receive more appropriate hormonal treatment. PET may also contribute significant prognostic information that may affect the decision to administer early adjuvant therapy to delay or prevent recurrence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREDICTING TUMOR RESPONSE TO FLUOROURACIL WITH PET Principal Investigator & Institution: Bading, James R.; Radiology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: There is a substantial need to develop accurate methods for predicting individual response to chemotherapy. Imaging of radiolabeled chemotherapeutic drugs with PET provides one approach to this problem. However, the usefulness of PET with drugs that are rapidly broken down in vivo, such as 5-fluorouracil (FU), is limited by the inability of the methodology to directly identify the molecular association of the
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radiolabel. Our long range objective is to develop PET as a tool for predicting response to chemotherapy and individualizing regimens for treating neoplastic disease. Our intermediate range objective is to develop clinically-practical PET techniques for predicting tumor response to FU. In order to be effective, FU must be taken up by tumor cells and anabolized to fluoronucleotides, which in turn interfere with DNA and RNA synthesis. Investigators at Heidelberg, Germany, recently reported positive correlation between tumor response to FU and tumor retention of radiolabel from [18F]FU as measured in PET in 17 patients undergoing treatment for metastatic colon cancer. While very promising, this study did not address the influence of recirculating, labeled catabolites of [18F]FU on the PET images, and the imaging technique used provides little information about the kinetics of FU in tumors. We are developing a new approach in which biomodulation is used to create an in vivo imaging technique capable of measuring tumor transport and metabolism of FU per se. Specifically, we pretreat with ethynyluracil (EU), a potent inhibitor of FU catabolism, to prevent degradation of [18F]FU and thereby improve the sensitivity of PET to those aspects of FU pharmacokinetics most closely related to tumor response. We have shown in preclinical studies with a rat colon tumor model that cellular uptake and anabolism of FU can be accurately measured by mathematical modeling of data obtained with our "PET/[18F]FU+EU"technique. The specific aims of the proposed study are (1) to evaluate our "PET[18F]FU+EU" technique for predicting tumor response to a form of therapy in which the technique is very closely related, viz., FU modulated by EU ("FU+EU"); and (2) to repeat the Heidelberg study "PET/[18F]FU") in a larger group of patients with colon cancer. The timeliness of Aim 1 is enhanced by current Phase II clinical trials of FU+EU and new indications of the importance of FU catabolism as a mechanism of tumor resistance to the drug. While PET and [18F]FU may provide information related to thymidylate synthase (TS), the primary target of FU, the imaging techniques does not measure TS inhibition directly. In the proposed study, TS concentration in tumor, a known correlate of tumor response, will be measured via tumor biopsy prior to therapy. Multiple regression analysis will be used to evaluate combination of parameters derived from PET and ex vivo TS assays as predictors of tumor response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREDICTION OF LUPUS OUTCOME BY GENE EXPRESSION PATTERNS Principal Investigator & Institution: Winchester, Robert J.; Professor; Pediatrics; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Support is sought for performing mechanistic studies to define the gene expression profiles of glomeruli isolated from biopsy sections of lupus glomerulonephritis with the overall goals of determining whether the glomerular gene expression phenotype will predict outcome and efficacy in an ongoing parent trial. The parent trial compares administration of CellCept versus IV Cytoxan for initiating control of biopsy-proven lupus nephritis. We have demonstrated the feasibility of studying gene expression profiles by microarray analysis in glomeruli isolated from frozen biopsy sections by laser microdissection t6 characterize the molecular pathologic mechanisms leading to lupus nephritis. This work revealed considerable heterogeneity in gene expression patterns in samples classified as proliferative glomerulonephritis, suggesting the feasibility of lupus renal biopsy subclassification by gene expression criteria. The expressed genes formed 8 main
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clusters and the presence or absence of genes comprising these clusters in a given sample divided the biopsies into 3 distinct types. The hypothesis underlying the proposed studies is that differences in molecular pathologic mechanisms revealed by the various transcriptional phenotypes will predict the heterogeneous natural history and therapeutic outcome of lupus. The first aim of the proposed mechanistic studies is to cluster glomerular gene expression patterns in diagnostic renal biopsies performed in the current trial and use them to extend understanding of pathways involved in the molecular pathogenesis of lupus glomerulitis. Parallel quantitative PCR for selected genes found through the microarray assessment will be performed to validate the patterns found and determine if their differential expression can be used as a surrogate. The second aim will correlate the clusters and pathways with conventional pathologic features to identify the molecular basis of the pathologic findings. The third aim will determine whether particular outcomes of the trial could be predicted by the gene expression phenotype of the initial renal biopsy. In particular we will address, first, whether one gene expression type, characterized by apoptosis, TNF signaling and fibrosis, is highly correlated with poor outcome and thus predict the subset of nonresponders to Cytoxan or CellCept. Second, whether CellCept will prove to be efficacious in a different gene expression subset, suggesting it could be used in these cases as a less toxic alternative to Cytoxan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA
PROGNOSTIC
MARKERS
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CUTANEOUS
Principal Investigator & Institution: Pinkel, Daniel D.; Professor; Cancer Center; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Cutaneous melanoma presents a significant health problem in Western Europe, Australia, and the United States. Americans in the United States currently have approximately a 1 in 75 lifetime risk developing this disease. If melanoma is not excised before it metastasizes the prognosis is poor. Recent evaluation of adjuvant treatments such as interferon alpha indicate the ability to prolong survival in patients with occult metastases, so identification of these patients is highly important. The goal of this proposal is to develop DNA copy number and gene expression markers in the primary tumor that will improve the ability to determine if clinically significant metastasis has occurred by the time of diagnosis. Sentinel lymph node (SLN) biopsy, coupled with several other characteristics of the primary tumor such as thickness and ulceration, are currently the best prognostic indicators. The finding of malignant cells in a sentinel node is a definite sign that the disease has begun to spread. but negative nodes do not guarantee a good outcome. A substantial proportion of all cases of metastatic melanoma come from patients who were SNL- at diagnosis. Thus improving the ability to determine which patients were at elevated risk of progression would have substantial medical benefit. In this project we w ill study primary tumors and corresponding metastases from a cohort of 700 patients that underwent SLN biopsy at UCSF, and an additional set of 100 primary tumors of Acral Lentiginous Melanoma (ALM), to detect DNA copy number changes and gene expression changes that distinguish primary tumors that metastasize from those that do not. Screening for DNA copy aberrations will be performed using array comparative genomic hybridization (array CGH) which has recently been developed in our laboratories. Candidate genes will be identified based on the copy number aberrations, and the prognostic power of the expression levels of these candidates will be evaluated. Using an independent set of
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tumors from the SLN cohort, we will validate the ability of these markers to: 1) distinguish patients that develop metastases from those that do not, and 2) to distinguish patients with negative sentinel nodes that develop metastases from those with negative nodes that remain disease free. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGNOSTIC VALUE OF TELOMERE DNA IN PROSTATE BIOPSY Principal Investigator & Institution: Griffith, Jeffrey K.; Professor and Chair; Biochem and Molecular Biology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 08-MAY-2000; Project End 31-MAR-2004 Summary: (Applicant's Description) Assessing prognosis of tumor growth potential in biopsy material is vital to choosing an appropriate therapy in prostate cancer. However, definitive molecular markers on which to base a prognosis are limited. Telomere DNA, the tandem six-base nucleotide repeats that cap and protect chromosome ends, are typically shorter in cancer cells. This suggests that telomere length may be an important determinant of tumor progression. A new slot blot assay which measures Telomere DNA Content (a proxy for telomere length) was developed by the Principal Investigator using tumor tissue. Results of this assay indicate that reduced telomere DNA content in breast cancer is correlated with aneuploidy (p less than 0.002) and metastasis (p less than 0.05) and in prostate cancer with reduced survival (p less than 0.004) and increased disease recurrence (p less than 0.0001). In Phase I, we will extend and refine the telomere DNA content assay to accommodate prostate needle-core biopsy specimens. In Phase II, we will utilize the assay to conduct a retrospective case-control study of archival prostate needle-core biopsies. The telomere DNA content data will be correlated to patient survival and the results evaluated to ascertain the predictive value of telomere DNA content in prostate biopsy samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTON MR SPECTROSCOPIC IMAGING IN HUMAN BREAST CANCER Principal Investigator & Institution: Barker, Peter B.; Associate Professor; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-DEC-2003 Summary: (provided by applicant): Breast cancer is the most common form of cancer in women. In the year 2000, it is predicted that approximately 180,000 new cases of breast cancer will be diagnosed in the United States, and 40,000 women will die from the disease. The key to successful treatment of breast cancer is early diagnosis, and the use of widespread mammography screening has resulted in significant improvements in breast cancer survival rates. However, a major problem with mammography is a lack of specificity; 70-80% of suspicious lesions on mammography referred for biopsy ultimately have a benign final diagnosis. These "unnecessary" biopsies represent a significant economic burden on health care systems, and are also invasive and unpleasant for the patient. Therefore, there is a need for the development of new noninvasive, cost-effective, and safe imaging procedures with enhanced specificity and sensitivity. Proton MR spectroscopic imaging (MRSI) is a non-invasive metabolic imaging technique, which has yet to be applied to human breast cancer. Preliminary data from our group and others, based on cell preparations, in vitro studies and singlevoxel human spectroscopy, suggest that an elevated composite choline signal (detected
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in the proton MR spectrum) is a marker of malignant breast disease. Benign lesions and normal breast tissue have little or no detectable choline signal. However, technical developments are required before proton MRSI can become a clinical procedure for evaluating breast cancer. These include maximizing spatial resolution, optimizing water and lipid suppression techniques, development of quantitation methodology, and providing whole breast coverage within a clinically acceptable scan time. We will develop and test these techniques in years one and two of this proposal (phase I, R21), and in years 3 and 4 (phase II, R33) we will apply these techniques to a trial of proton MRSI in human breast cancer. Specifically, choline levels will be compared between histologically defined tissue types, in patients who are scheduled for breast biopsy. The sensitivity and specificity of proton MRSI in this patient group will be determined. The techniques developed in this proposal will also assist in the translation of proton MRSI to other organ systems and pathologies, and increase the acceptance of clinical proton MRSI as a diagnostic imaging modality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: QUANTITATIVE ASSESSMENT OF IRON OVERLOAD BY MRI Principal Investigator & Institution: Wang, Zhiyue J.; Assistant Professor; Radiology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2000; Project Start 30-SEP-1998; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract) The long-term objective of this proposal is to develop in vivo magnetic resonance (MR) techniques for a reliable non-invasive assessment of iron stores in patients with iron overload due to chronic transfusion therapy for diseases such as thalassemia, sickle cell disease and other blood disorders. The specific aims of the project are: 1a) to study the T2 of liver tissue under iron overload conditions in vivo and correlate with biopsy determined iron level; 1b) to measure T2 of cardiac tissue from autopsied human hearts and an iron overload gerbil model in vitro and correlate with a chemically determined iron level; 2) to assess a new, non-invasive magnetic susceptibility measurement technique, "the contact reference method," that will be applicable for outer myocardium; (3) to develop a non-invasive susceptibility measurement technique for the liver using blood vessel signal as internal reference. An accurate assessment of body iron stores plays a central role in the management of chronically-transfused patients. Current body iron assessment methods are limited to liver biopsy or superconducting quantum interference device (SQUID) susceptometry, but neither is convenient for routine use, and there is no non-invasive technique to evaluate the heart. The focus of this application centers on developing techniques for the liver examination, and characterizing MR properties of heart tissue under iron overload conditions. A spectroscopy sequence with minimum TE 1.5 ms will be used to measure the liver T2 in a 3x3x3 cm3 volume in 30 patients, and correlate the results with biopsy determine iron level; In vitro T2 of 108 specimens from 9 human autopsy hearts and 192 specimens from 48 gerbil hearts will be measured and correlated with the tissue iron level. The magnetic susceptibility of the same human autopsy hearts and gerbil hearts will be evaluated by a contact reference technique: the resonant frequency differences across the interface of tissue and saline reference, obtained by using 3-dimensional gradient echo imaging, will be used to qualify the tissue susceptibility. Finally, an in vivo liver susceptibility measurement technique will be developed: sequential 2-dimensional navigator echo imaging will be used to measure frequency offset, the magnetic susceptibility of the liver will be obtained. For each aim, statistical analysis using linear regression will be done to assess the reliability of iron level predicted by the MR technique.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RCT OF SAME IN ALCOHOLIC LIVER DISEASE Principal Investigator & Institution: Mendler, Michel H.; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 31-MAY-2007 Summary: (provided by applicant): Background: Alcoholic liver disease is one of the most important causes of chronic liver disease in this country. There is currently no treatment for chronic alcoholic liver disease other than abstinence. Hepatic methionine metabolism is abnormal in these patients and one of the consequences is depletion of Sadenosylmethionine (SAMe) levels, which can affect numerous important cellular processes. SAMe has been increasingly utilized for the treatment of liver diseases although the protective mechanisms remain unclear. A recent randomized double-blind trial using SAMe in patients with alcoholic liver disease and found improvement in 2year survival in those with less advanced liver disease. However, important changes in methionine metabolism and histological changes were not included in the study. Aim: The goal of this study is to determine the effect of SAMe administration on key metabolic abnormalities of the methionine cycle and on the recovery from alcoholic liver disease. Methods: This is a randomized, double blind, placebo-controlled trial. Thirty patients with stable alcoholic hepatitis (Maddrey Score < 32) without cirrhosis who meet entry criteria will receive either 400 mg of SAMe (n=15) or placebo (n=15) three times a day for the duration of one year. History, physical assessment, various blood tests and a liver biopsy will be performed prior to treatment. Patients will have repeat blood tests on subsequent follow-up visits every month for the first two months, then every two months thereafter. They will also be encouraged to abstain from alcohol during these visits. A post-treatment liver biopsy will be obtained at the end of the trial. The primary outcome parameters include serum homocysteine, SAMe and TNFalpha levels, and the expression of key hepatic enzymes of the methionine cycle and of hepatic SAMe and glutathione levels. Histological progression of alcoholic liver disease, clinical and biochemical indices of liver disease, and quality of life assessment will also be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REDUCING BENIGN BREAST BIOPSIES WITH COMPUTER MODELING Principal Investigator & Institution: Baker, Jay A.; Radiology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant):The primary objective of this project is to improve the diagnosis of breast cancer and reduce unnecessary benign breast biopsies. An artificial neural network computer-aided 'advisor' will be constructed to assist radiologists in deciding which solid breast masses warrant immediate biopsy and which can be safely observed. Up to 80% of breast biopsies result in a benign diagnosis because benign and malignant masses often appear similar at mammography and sonography. We have previously developed computer models - artificial neural networks - for predicting breast cancer based on mammogram features and the patient's medical history. Models built with only mammography findings and the patient's age demonstrate good preliminary results, potentially eliminating 22% of benign biopsies while identifying all cancers. The principal innovative features of this project are: (1) the focus on solid breast masses by incorporating high-resolution ultrasound features, and
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(2) the use of a novel, standardized lexicon devised by the American College of Radiology for describing breast ultrasound findings. The goal of the proposed project is to maintain near perfect sensitivity (>98%) - similar to the accuracy of the present clinical practice of short-interval follow-up for 'probably benign' lesions - while theoretically reducing the number of biopsies of benign breast masses by half. Mammogram and ultrasound features will be established for a large retrospective database of approximately 1000 biopsy-proven cases. Artificial neural networks will be constructed with 'supervised' training to predict which masses are very likely benign and which are suspicious for malignancy. The computer predictive models will be tested on a prospective validation database of approximately 1350 cases with known biopsy results. Performance will be evaluated in terms of fraction of benign biopsies avoided while maintaining greater than 98% sensitivity. An interobserver variability study will determine whether the computer model reduces interpretation error and inconsistency between observers. Assuming performance approaching that of the preliminary model, a decision aid based on this model will be ready for prospective clinical trials at the conclusion of this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SELENIUM AND LUNG CANCER RISK IN ASBESTOS WORKERS Principal Investigator & Institution: Gottschall, Eva B.; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2002; Project Start 21-AUG-2000; Project End 31-JUL-2005 Summary: (Applicant's Description) Lung cancer accounts for more cancer deaths in the United States than breast, prostate and colorectal cancer combined. Efforts to improve early detection, develop successful screening programs and find effective chemopreventive agents are desirable. Selenium has shown promise as a cancer chemopreventive agent in animal and human studies. A putative mechanism of selenium's anticarcinogenic activity is its integral part in cellular antioxidant systems. Asbestos-exposed workers have a well established increased incidence of lung cancer, and asbestos carcinogenesis is thought to involve activated oxygen species. In a crosssectional study of asbestos-exposed workers, a large number of individuals were found to have moderate sputum atypia (28 percent), a marker of lung cancer risk. The major hypothesis of this proposal is that asbestos-exposed workers treated with oral seleniumrich yeast (200gg/day) will show significant improvement in intermediate end-point biomarkers of lung cancer risk compared to placebo; and furthermore, changes in markers of lung cancer will be accompanied by decreases in markers of oxidative cellular damage. The study design is a randomized, placebo-controlled, double blind trial of asbestos-exposed construction trades workers using high selenium yeast supplementation. Markers of lung cancer risk to be examined include sputum cytologic atypia, endobronchial metaplasia/dysplasia, and nuclear morphometry of sputum and endobronchial biopsy specimens. The mechanism of action of selenium will be investigated using markers of oxidative cellular damage, including 8hydroxydeoxyguanosine (a marker of DNA damage), malondialdehyde (a marker of lipid peroxidation), and 8-iso-prostaglandine F2, (a marker of lipid peroxidation), before and after the intervention. The proposed study will assess whether selenium is effective in reversing premalignant lesions indicative of increased lung cancer risk and elucidate potential mechanisms of action of selenium. As such, this study will provide a critical foundation to further establish selenium as a potential chemopreventive agent for human lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SELENIUM BASED CHEMOPREVENTION Principal Investigator & Institution: Coltman, Charles A.; Chairman; Ctrc Research Foundation San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2004 Summary: We propose to evaluate the chemoprevention of prostate cancer among men who are, by virtue of having been diagnosed with High Grade Prostatic Intraepithelial Neoplasia (HGPIN), at a greatly elevated prostate cancer risk. After a biopsy-based diagnosis of HGPIN, each subject will be re- biopsied to minimize the probability he has PC missed by the first biopsy. Subjects will then be randomized to either 200 mcg/day of selenium in the form of L-selenomethionine or to a matching placebo. After randomization, each subjective will be followed for three years. The primary endpoint of this study is PC. Secondary endpoints will include two established Surrogate Endpoint Biomarkers (SEBs): Ki-67 evaluation of cell proliferation and TUNEL evaluation of apoptosis. Each of these endpoints will be evaluated for reproducibility, predictive association with subsequent PC, and for response to selenium supplementation. In addition, we propose a developmental investigation of two potential SEBs that are based on machine vision histometry: erosion of the basal cells of prostatic ducts and histometric characteristics of chromatin patterns. These developmental SEBs will be investigated for reproducibility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SENSITIZATION TO THERMORADIOTHERAPY IN HUMAN XENOGRAFTS Principal Investigator & Institution: Leeper, Dennis B.; Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2007 Summary: Project 1 serves the program by testing the hypothesis that acute acidification by lactic acidosis will enhance thermosensitization and selectively sensitize melanoma xenografts to radiotherapy. Protocols were established for acute acidification to less than or equal too pH3 6.3 and oxygenation of melanoma has uniquely high activity of H+ linked monocarboxylate transporters (MCT, a.k.a. lactate symport) that are the major membrane proton exchange. Although thermosensitization by acidification was demonstrated, radiation must be combined with hyperthermia to achieve local control. Five specific aims will test the hypothesis and investigate mechanisms of melanoma acidification. Aim 1 will investigate inhibition of mitochondrial respiration by metaiobenzylguanidine (MIBG) on melanoma acidification and oxygenation for sensitization to thermoradiotherapy. Variation in glycolytic/respiratory ratio among frozen melanoma biopsy cell suspensions will indicate relative susceptibility to MIBG. Aim 2 will investigate inhibition of the MCT either by alpha-cyano-4-hydroxy-cinnamic acid (CNCn) or by Ionidamine on acidification of melanoma and sensitization to thermoradiotherapy. The activity of the plasma membrane MCT among stored melanoma biopsy cell suspensions will indicate relative susceptibility to CNCn or Ionidamine. Aim 3 will identify the utility of combining MIBG and CNCn as a cocktail to acidify and oxygenate all melanomas. Melanomas with high rates of respiration will be sensitive to MIBG, and those with high rates of glycolysis sensitive to CNCn. In each protocol excess glucose must be combined with inhibitors to fuel lactate production. Two different F2 melanomas xenografts in nude mice will be studied that differ in vascularity, radiation sensitivity and expression of heat shock proteins. Tumor growth delay will be compared with tibial bone marrow toxicity to establish therapeutic gain.
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Cellular radiation response parameters in vitro will be determined in Project 3. Project 1 provides mice with melanoma xenografts to Project 2, so that together with Core A, biological endpoints can be investigated to predict response of melanomas and normal tissues to treatment pH9, pHi, 23Nai, pO2, oxygen consumption, bioenergetics and blood flow. Aim 4 supports Project 3 to determine the effect of acute acidification on apoptosis and the relationship with hyperthermia-induced upregulation of hsp70 in DB1 xenografts grown up from cell stably transfected with the gene for enhanced green fluorescent protein (egfp) under control of the hsp70 promoter. Aim 5 with Project 3 supports Project 4 to confirm whether nucleolin translocation is a determinant of heat response in vivo by measuring nucleolin movement from the nucleolus into the nucleoplasm in DB-1 xenografts as a function of acidification during hyperthermia. Acute tumor acidification will have the clinical effect of increased tumor temperature with additional benefit from increased tumor oxygenation. These results will help direct a Phase I/II trial conducted by Dr. Douglas Fraker, Univ. of Penn. To demonstrate the effects of acidification of melanoma response to limb perfusion with melphalan at 42 degrees Centigrade. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SOLID STATE BETA IMAGING SENSOR FOR IMAGE GUIDED SURGERY Principal Investigator & Institution: Entine, Gerald; President; Radiation Monitoring Devices, Inc. 44 Hunt St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Nuclear Medicine imaging has been widely used to preoperatively image structures of interest for excisional biopsy. Radio-guided intraoperative procedures utilizing radiotracers have facilitated a cost-effective, highly specific means to locate suspect tissue and access it for pathologic analysis. The result of radio-guided surgery is increased tissue specificity obtained for biopsy, minimally accessed incisions, and the reduction of inpatient hospital utilization with an improved patient recovery. Nuclear medicine based surgical guidance with non-imaging gamma detector probes is gaining in acceptance and popularity. The main drawback of nonimaging guidance is the lack of ancillary information of the surveyed area, such as distinction between two neighboring radioactive regions, which can be overcome with an intraoperative imaging probe. Also, the highly penetrating gamma radiation arising from other parts of the body increases the background and limits the practical use of these probes. We propose to address these limitations by designing a new-generation intraoperative probe intended to rapidly image the tumor bed with short-range beta rays. This new design will be based on a solid-state, compact readout sensor coupled to a high resolution, high SNR converter. When developed, this detector will allow accurate delineation of the tumor, thus facilitating precise resection. PROPOSED COMMERCIAL APPLICATIONS: Advances in radiopharmaceuticals has dramatically escalated the use of intraoperative probes in surgery. The proposed research will provide a new class of digital imaging probes, which will exploit these advances allowing for complete and accurate tumor resection with enhanced quality of health care and increased lifespan of patients. This new imaging technology has enormous potential in both medical and non-medical applications. The estimated market size for probes is well over a hundred million dollars. A significant fraction of this market represents areas where the proposed technology will have a major impact. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECTROSCOPIC DYE LOCALIZATION: SENTINEL LYMPH NODES Principal Investigator & Institution: Benaron, David A.; Assistant Professor; Spectros Corporation 4370 Alpine Rd, Ste 108 Portola Valley, Ca 94028 Timing: Fiscal Year 2002; Project Start 13-AUG-1999; Project End 31-MAY-2004 Summary: (provided by applicant): Spectros Corporation and collaborators/consultants at Stanford University, Texas Tech U., Amersham Pharmacia Biotech, and Protein Design Labs, will continue development of a new, fluorescent contrast agent and imaging system, created to improve the accuracy of identifying sentinel lymph nodes during breast cancer surgery. The end result of Phase II will be a lymphatic-targeted optical contrast agent and real-time clinical imaging system, ready for human testing. In Phase II, the contrast agent (SPX-1 03), first synthesized in Phase I, will be optimized for brightness, tested for toxicity and mutagenicity, and synthesized under GMP protocols. The imaging system will be adapted for O.R. use, including custom lens systems and operating software. The system and agent will be tested in combination in animals, and then submitted to the FDA in preparation for human studies. The short-term goal is to create an imaging system and agent that exceed the sensitivity and specificity of the current dye and technetium methods, thus allowing for a more limited and patientspecific procedure without need for the injection of radioactive tracers. Ultimately, our long-term goal is to develop targeted agents to detect only cancerous nodes, allowing the 68 percent of patients who are node-negative to skip nodal biopsy altogether, and allow the remainder to undergo a patient-specific procedure. PROPOSED COMMERCIAL APPLICATIONS: Spectros will develop a commercial guidance system for sentinel node biopsy. Breast cancer is a leading cause of death in women, and accurate node biopsy is key to effective treatment selection and to patient survival. Over 150 K U.S. women/year are sentinel node biopsy candidates. The market for an improved lymph biopsy system is estimated at $150 MM/year. Therapeutic platform extensions to real-time imaging of prostate, colon, colon, melanoma, and lymphatic cancers are envisioned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TARGETED OPTIMIZATION
PROSTATE
BIOPSY
USING
MATHEMATICAL
Principal Investigator & Institution: Davatzikos, Christos; Associate Professor; Radiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Prostate cancer is the second leading cause of death for American men. However, there is currently no imaging modality that can reliably detect cancer in the majority of cases. Therefore, needle biopsy of the prostate has been widely used as a gold standard for the diagnosis and staging of prostate cancer, when elevated prostate specific antigen (PSA) levels are measured. Following the widespread use of sextant biopsy, several enhanced random systematic biopsy methods have been adopted by different groups in an effort to reduce the significant number of cases remaining undetected at initial biopsy, mainly by using additional needles, albeit with limited success. The need to more thoroughly understand the performance of all these random systematic sampling methods has led to several computer simulation studies that utilize whole-mounted histological stained sections from prostatectomy specimens in order to estimate the performance of different biopsy approaches. However, to date there has been no mathematically rigorous attempt to precisely determine where the needles should be placed in order to maximize probability of cancer detection. The
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overall goal of this project is to develop and clinically test a computer-based methodology for optimal sampling of the prostate during biopsy, so that the probability of cancer detection is maximal, based on statistics obtained by applying an advanced image analysis methodology to whole-mounted sections of radical prostatectomy specimens. We thus propose to develop and clinically test a targeted prostate biopsy method. By this we mean that the exact spatial locations of biopsy sites will be determined using mathematical optimization methods, rather than approximate biopsy locations being defined in terms of a rough subdivision of the prostate, which is the current practice. Histological sections from 281 diverse specimens will be used to determine the spatial statistics of prostate cancer. A methodology for elastic shape transformation will be developed and used to accurately overlay images from different specimens, by removing inter-individual morphological variability. Optimal biopsy sites will be determined by mathematical optimization, i.e., by finding the needle coordinates that maximize probability of cancer detection, taking into consideration expected errors in needle placement. Deformable registration algorithms will be developed for overlaying the optimal biopsy sites on a patient's MR images. The optimal sampling method will be validated on an independent patient population, under precise intra-operative MR guidance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE EFFECT OF A PROBIOTIC ON HEPATIC STEATOSIS Principal Investigator & Institution: Diehl, Anna M.; Professor and Chief; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. NAFLD includes a spectrum of hepatic pathology that ranges from fatty liver (steatosis) at the most clinically indolent extreme, to cirrhosis at the opposite extreme where most liver specific morbidity and mortality occurs. Indeed, NAFLD is now thought to be responsible for most of what was once classified as 'cryptogenic cirrhosis'. Cryptogenic cirrhosis accounts for half of the annual liver-related deaths. The study of NAFLD has been hindered by the lack of an easily measurable, clinically relevant outcome measure. Safe, inexpensive, well-tolerated treatments for NAFLD are greatly needed. Recent breakthroughs using animal models have advanced understanding of the pathogenesis of NAFLD and provide hope for the development of effective treatments. Based on extensive work in our own laboratory, our OVERALL HYPOTHESIS is that alcohol and lipopolysacchride (LPS) production by intestinal bacterial overgrowth (IBO) cause inflammatory signaling in the liver that leads to hepatic insulin resistance and NAFLD. To evaluate this possibility, we treated a murine model of NAFLD with probiotics or anti-tumor necrosis factor a (TNF) antibodies. Indeed, both treatments decreased activation of well-defined molecular inflammatory pathways and improved steatosis by biopsy. This exciting preliminary data provides rationale for studying probiotics in humans. Therefore, this project has a single SPECIFIC AIM: to determine if probiotic therapy can decrease hepatic steatosis in humans with NAFLD. We propose a doubleblinded, randomized, placebo-controlled four month pilot study of 30 patients with NAFLD. The main outcome measure will be grade of hepatic steatosis evaluated by biopsy. We will also measure steatosis by magnetic resonance spectroscopy (MRS). The possibility that probiotics, which are safe, well-tolerated and natural therapies, might improve NAFLD is exciting because liver-related morbidity and mortality are late complications of most chronic liver diseases, including NAFLD. Thus, the safety profile
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of probiotics makes them an attractive treatment option for a disease that will likely require chronic therapy. If the efficacy of probiotics is established one type of chronic liver disease, the possibility that similar biological therapies might benefit other chronic inflammatory states would merit further evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TISSUE AND CELL RESERVOIRS FOR HIV Principal Investigator & Institution: Gartner, Suzanne; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Success in treating HIV/AIDS is critically dependent upon a thorough and accurate understanding of occult infection---where and how HIV persistence is maintained. This proposal focuses on the macrophage and follicular dendritic cell (FDC) as cellular reservoirs for HIV, and bone marrow and brain as tissue reservoirs. Although they have received comparatively little attention, these cell and tissue compartments most probably represent HIV reservoirs of considerable significance. Importantly, each appears capable of serving as a sanctuary for latent HIV infection. We propose here to determine if, indeed, these cells and tissues can serve as latently infected hosts able to yield infectious particles that can seed the body. We seek to identify patterns of HIV trafficking between lymphoid tissues and the Central Nervous System, and determine if the brain can reseed the periphery with HIV. We also seek to identify cell and tissue reservoirs for antiretroviral drug-sensitive, versus drugresistant, HIV. For these studies, HIV genotyping will be performed using contemporaneously-collected ante-mortem bone marrow and excised cervical lymph node biopsy specimens, in conjunction with patient-matched plasma, cerebrospinal fluid (CSF), and separated blood monocyte and T-lymphocyte specimens collected concomitantly, as well as prior to, and following biopsy. Two regions of the HIV genome will be examined, the V1-V4 region of the envelope gene, and a 1.2kb fragment which includes the protease gene and that portion of the reverse transcriptase gene which codes for most of the antiretroviral resistance mutations of significance. To optimally address the question of whether the brain can seed the periphery with HIV, we will evaluate the HIV species present not only within the lymph node (LN) CD4+ Tcell population, but also those associated with LN germinal center follicular dendritic cells (FDC). These investigations will be complemented with studies of post-mortem tissues. In addition, we seek to identify events in bone marrow associated with systemic virologic failure. Attention will be paid to HIV expression and monocyte/macrophage activation in marrow. Immunohistochemistry and flow cytometry methods will be used. These studies will yield important new information regarding HIV reservoirs, as well as the contributions of events in bone marrow to HIV immunopathogenesis and disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT OF ENDOMETRIOSIS-ASSOCIATED PELVIC PAIN Principal Investigator & Institution: Guzick, David S.; Professor and Chair; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Approximately one-third of women with chronic pelvic pain have endometriosis. Surgical treatment of endometriosis with laparoscopic excision of implants and lysis of adhesions is often successful in reducing pain in the
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short term. Furthermore, several postoperative medical treatments have been shown to be efficacious in maintaining pain reduction for as long as the medication is continued. After stopping the medication, however, the level of pain tends to trend upwards towards pre-treatment levels. The desired postoperative treatment is one that is can be used for a long period of time, so as to minimize the chance of pain recurrence. Simplicity of administration and cost-effectiveness are other desirable characteristics of an ideal postoperative regimen. The only FDA approved 12-month treatment for endometriosis-associated pain is a combination of leuprolide acetate (a GnRH analog), 11.25 mg IM q 12 weeks, and norethindrone acetate, 5 mg PO daily. Use of this regimen has been constrained by its complexity and cost. As an alternative, the continuous use of oral contraceptives has been advocated as a practical, inexpensive strategy for long-term medical treatment of endometriosis-associated pain. Although such an approach is frequently used in clinical practice, there has been no clinical trial of its efficacy. The goal of this project is to compare the efficacy and cost-effectiveness of continuous oral contraceptives and leuprolide+norethindrone in the postoperative treatment of endometriosis-associated pelvic pain. Investigators at the University of Rochester School of Medicine and Harvard Medical School will recruit 194 women for randomization to one of the two treatments, each of which will continue for 48 weeks. Randomization will occur after biopsy-proven endometriosis is established. Pelvic pain and quality-of-life assessments will be obtained at regular intervals. The recruitment goal is 88 subjects per arm after a 10% drop-our rate. Change scores for these measures will be compared between the two treatments. The study has 80% power to test non-inferiority of oral contraceptives at the 5% level of significance, using a 1-point difference in the change scores for pain as the threshold. In addition, a cost-effectiveness analysis will be performed by calculating the cost per unit reduction in pain score for each treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VALIDATION OF NON-INVASIVE DIAGNOSIS OF HP Principal Investigator & Institution: Snyder, John D.; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): H. pylori causes gastritis, duodenal ulcers and is strongly linked to gastric cancer, but most infections are asymptomatic. No group of GI signs and symptoms have been shown to predict infection or associated disease. At present, no validated non-invasive tests exist to diagnose active H. pylori infection in children. Despite this, many clinicians test for H. pylori in children with gastrointestinal (GI) symptoms and will treat if the infection is "found". The urgent need for a rational approach to treatment of H. pylori in children is underscored by the fact that more than 11 million U.S. children are infected, using a conservative prevalence estimate of 15%. A randomized controlled trial of the effect of H. pylori eradication on GI symptoms in children is clearly needed. Before conducting such a trial, important preliminary validation studies are required. This study will test the overall hypothesis: that it is feasible to use non-invasive tests and a symptom assessment instrument (SAI) to determine the presence/absence of H. pylori infections in children with GI symptoms and can be used as diagnostic surrogates for the more invasive endoscopy and biopsy. Since commercial serology tests are not accurate in children, aim 1 will be to determine the feasibility of using the non-invasive 13C urea breath test and stool antigen test, preformed at the time of previously scheduled endoscopy and biopsy, to accurately detest active H. pylori infection in children and thus be considered as potential effective surrogate tests for diagnosis. Preliminary data on the sensitivity, specificity, positive and
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negative predictive value of these tests will also be compared using the standards for diagnosis established by the FDA. Aim 2 will be to determine the feasibility of using a pediatric gastrointestinal (GI) symptom assessment instrument (SAI), administered at the time of endoscopy, to evaluate GI symptoms of children with symptomatic H. pylori infection. Preliminary data will be obtained on the ability of the SAI to measure the severity of signs and symptoms based on endoscopic and histologic findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “biopsy” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for biopsy in the PubMed Central database: •
Active Surveillance for Scrapie by Third Eyelid Biopsy and Genetic Susceptibility Testing of Flocks of Sheep in Wyoming. by O'Rourke KI, Duncan JV, Logan JR, Anderson AK, Norden DK, Williams ES, Combs BA, Stobart RH, Moss GE, Sutton DL.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120069
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Anti-CagA Immunoglobulin G Responses Correlate with Interleukin-8 Induction in Human Gastric Mucosal Biopsy Culture. by Ando T, Perez-Perez GI, Kusugami K, Ohsuga M, Bloch KC, Blaser MJ.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95959
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Brachyspira aalborgi Infection Diagnosed by Culture and 16S Ribosomal DNA Sequencing Using Human Colonic Biopsy Specimens. by Kraaz W, Pettersson B, Thunberg U, Engstrand L, Fellstrom C.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87436
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Clinical, radiographic, endoscopic, bronchoalveolar lavage and lung biopsy findings in horses with exercise-induced pulmonary hemorrhage. by Doucet MY, Viel L.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=339202
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Comparison of Genotyping Helicobacter pylori Directly from Biopsy Specimens and Genotyping from Bacterial Cultures. by Park CY, Kwak M, Gutierrez O, Graham DY, Yamaoka Y.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165374
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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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Comparison of processing techniques for detection of Pneumocystis carinii cysts in open-lung biopsy specimens. by Gay JD, Smith TF, Ilstrup DM.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271601
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Detection and Verification of Mycobacterium avium subsp. paratuberculosis in Fresh Ileocolonic Mucosal Biopsy Specimens from Individuals with and without Crohn's Disease. by Bull TJ, McMinn EJ, Sidi-Boumedine K, Skull A, Durkin D, Neild P, Rhodes G, Pickup R, Hermon-Taylor J.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165291
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Detection of Helicobacter pylori in Paraffin-Embedded and in Shock-Frozen Gastric Biopsy Samples by Fluorescent In Situ Hybridization. by Russmann H, Feydt-Schmidt A, Adler K, Aust D, Fischer A, Koletzko S.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149697
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Development and application of genetic probes for detection of Enterocytozoon bieneusi in formalin-fixed stools and in intestinal biopsy specimens from infected patients. by Carville A, Mansfield K, Widmer G, Lackner A, Kotler D, Wiest P, Gumbo T, Sarbah S, Tzipori S.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170541
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Diagnosis of Mycoplasma pneumoniae Infection in Autopsy and Open-Lung Biopsy Tissues by Nested PCR. by Talkington DF, Thacker WL, Keller DW, Jensen JS.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104711
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Diagnosis of Pericardial Disease Using Percutaneous Biopsy Case Report and Literature Review. by Gupta K, Mathur VS.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161899
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Diagnostic Value of PCR for Detection of Borrelia burgdorferi in Skin Biopsy and Urine Samples from Patients with Skin Borreliosis. by Brettschneider S, Bruckbauer H, Klugbauer N, Hofmann H.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105180
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Direct Detection of Helicobacter pylori Mutations Associated with Macrolide Resistance in Gastric Biopsy Material Taken from Human Immunodeficiency VirusInfected Subjects. by Scarpellini P, Carrera P, Cavallero A, Cernuschi M, Mezzi G, Testoni PA, Zingale A, Lazzarin A.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130724
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Direct Detection of Legionella Species from Bronchoalveolar Lavage and Open Lung Biopsy Specimens: Comparison of LightCycler PCR, In Situ Hybridization, Direct Fluorescence Antigen Detection, and Culture. by Hayden RT, Uhl JR, Qian X, Hopkins MK, Aubry MC, Limper AH, Lloyd RV, Cockerill FR.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88195
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Endomyocardial biopsy in the evaluation of conditions leading to cardiac transplantation and in the evaluation of cardiac allograft rejection. by McAllister HA Jr.; 1995; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325211
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Evaluation of a Group-Specific 16S Ribosomal DNA-Based PCR for Detection of Helicobacter bizzozeronii, Helicobacter felis, and Helicobacter salomonis in Fresh
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and Paraffin-Embedded Gastric Biopsy Specimens. by De Groote D, Haesebrouck F, van Doorn LJ, Vandamme P, Ducatelle R.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87905 •
Evaluation of a Selective Transport Medium for Gastric Biopsy Specimens To Be Cultured for Helicobacter pylori. by Siu LK, Leung WK, Cheng AF, Sung JY, Ling TK, Ling JM, Ng EK, Lau JY, Chung SC.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105110
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Evaluation of performances of three DNA enzyme immunoassays for detection of Helicobacter pylori PCR products from biopsy specimens. by Monteiro L, Cabrita J, Megraud F.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230090
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Fast and Accurate Quantitative Detection of Helicobacter pylori and Identification of Clarithromycin Resistance Mutations in H. pylori Isolates from Gastric Biopsy Specimens by Real-Time PCR. by Lascols C, Lamarque D, Costa JM, Copie-Bergman C, Le Glaunec JM, Deforges L, Soussy CJ, Petit JC, Delchier JC, Tankovic J.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254337
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Fine-needle aspiration biopsy of the thyroid. by Suen KC.; 2002 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121968
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Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. by Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137534
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Heterogeneity of cag Genotypes in Helicobacterpylori Isolates from Human Biopsy Specimens. by Tomasini ML, Zanussi S, Sozzi M, Tedeschi R, Basaglia G, De Paoli P.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150293
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Immunohistochemical detection of a novel 22- to 25-kilodalton glycoprotein of Paracoccidioides brasiliensis in biopsy material and partial characterization by using species-specific monoclonal antibodies. by Figueroa JI, Hamilton A, Allen M, Hay R.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264039
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Isolation of Serpulina pilosicoli from Rectal Biopsy Specimens Showing Evidence of Intestinal Spirochetosis. by Trivett-Moore NL, Gilbert GL, Law CL, Trott DJ, Hampson DJ.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124848
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Molecular Evidence of Helicobacter cinaedi Organisms in Human Gastric Biopsy Specimens. by Pena JA, McNeil K, Fox JG, Versalovic J.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140399
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Mutation of p53 in Primary Biopsy Material and Cell Lines from Hodgkin Disease. by Gupta RK, Patel K, Bodmer WF, Bodmer JG.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46187
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Paracoccidioidesbrasiliensis 87-Kilodalton Antigen, a Heat Shock Protein Useful in Diagnosis: Characterization, Purification, and Detection in Biopsy Material via
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Immunohistochemistry. by Diez S, Gomez BL, Restrepo A, Hay RJ, Hamilton AJ.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153377 •
PCR-Based Diagnosis of Helicobacter pylori Infection and Real-Time Determination of Clarithromycin Resistance Directly from Human Gastric Biopsy Samples. by Chisholm SA, Owen RJ, Teare EL, Saverymuttu S.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87913
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Percutaneous biopsy of a pulmonary artery guided by computed tomography. by Velebit V, Hauser H.; 1995; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325268
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Quantitation of Pseudomonas aeruginosa in wound biopsy samples: from bacterial culture to rapid `real-time' polymerase chain reaction. by Pirnay JP, De Vos D, Duinslaeger L, Reper P, Vandenvelde C, Cornelis P, Vanderkelen A.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29046
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Rapid colorimetric hybridization assay for detecting amplified Helicobacter pylori DNA in gastric biopsy specimens. by Lage AP, Fauconnier A, Burette A, Glupczynski Y, Bollen A, Godfroid E.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228840
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Screening of Neonatal Calves for Persistent Infection with Bovine Viral Diarrhea Virus by Immunohistochemistry on Skin Biopsy Samples. by Grooms DL, Keilen ED.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120018
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Selective growth in serum-free hormone-supplemented medium of tumor cells obtained by biopsy from patients with small cell carcinoma of the lung. by Carney DN, Bunn PA Jr, Gazdar AF, Pagan JA, Minna JD.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319525
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Semiquantitative Detection by Real-Time PCR of Aspergillus fumigatus in Bronchoalveolar Lavage Fluids and Tissue Biopsy Specimens from Patients with Invasive Aspergillosis. by Rantakokko-Jalava K, Laaksonen S, Issakainen J, Vauras J, Nikoskelainen J, Viljanen MK, Salonen J.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193834
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Sentinel node biopsy for breast cancer: is it already a standard of care? A survey of current practice in an Italian region. by Zavagno G, De Salvo GL, Casara D, Del Bianco P, Rubello D, Meggiolaro F, Rossi CR, Pierobon M, Lise M.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=344740
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The Efficacy of Laboratory Diagnosis of Helicobacter pylori Infections in Gastric Biopsy Specimens Is Related to Bacterial Density and vacA, cagA, and iceA Genotypes. by van Doorn LJ, Henskens Y, Nouhan N, Verschuuren A, Vreede R, Herbink P, Ponjee G, van Krimpen K, Blankenburg R, Scherpenisse J, Quint W.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86006
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Transport and Storage of Fresh and Frozen Gastric Biopsy Specimens for Optimal Recovery of Helicobacter pylori. by Heep M, Scheibl K, Degrell A, Lehn N.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85756
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with biopsy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “biopsy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for biopsy (hyperlinks lead to article summaries): •
A brachytherapy template approach to standardize saturation prostatic biopsy. Author(s): Bott SR, Henderson A, McLarty E, Langley SE. Source: Bju International. 2004 March; 93(4): 629-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008745
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A hybrid breast biopsy system combining ultrasound and MRI. Author(s): Piron CA, Causer P, Jong R, Shumak R, Plewes DB. Source: Ieee Transactions on Medical Imaging. 2003 September; 22(9): 1100-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956265
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A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Author(s): Van Zee KJ, Manasseh DM, Bevilacqua JL, Boolbol SK, Fey JV, Tan LK, Borgen PI, Cody HS 3rd, Kattan MW. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 December; 10(10): 1140-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654469
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A novel technique for localization and excisional biopsy of small or ill-defined pulmonary lesions. Author(s): Daniel TM, Altes TA, Rehm PK, Williams MB, Jones DR, Stolin AV, Gay SB. Source: The Annals of Thoracic Surgery. 2004 May; 77(5): 1756-62; Discussion 1762. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15111180
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A randomized double-blind prospective study evaluating patient tolerance of transrectal ultrasound-guided biopsy of the prostate using prebiopsy rofecoxib. Author(s): Moinzadeh A, Mourtzinos A, Triaca V, Hamawy KJ. Source: Urology. 2003 December; 62(6): 1054-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665354
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A randomized, prospective cross-over trial comparing methylene blue-directed biopsy and conventional random biopsy for detecting intestinal metaplasia and dysplasia in Barrett's esophagus. Author(s): Ragunath K, Krasner N, Raman VS, Haqqani MT, Cheung WY. Source: Endoscopy. 2003 December; 35(12): 998-1003. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648410
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A real-time biopsy needle segmentation technique using Hough transform. Author(s): Ding M, Fenster A. Source: Medical Physics. 2003 August; 30(8): 2222-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12945988
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A retrospective observational study of primary cutaneous malignant melanoma patients treated with excision only compared with excision biopsy followed by wider local excision. Author(s): McKenna DB, Lee RJ, Prescott RJ, Doherty VR. Source: The British Journal of Dermatology. 2004 March; 150(3): 523-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030337
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Abnormal liver function tests following bone marrow transplantation: aetiology and role of liver biopsy. Author(s): Ho GT, Parker A, MacKenzie JF, Morris AJ, Stanley AJ. Source: European Journal of Gastroenterology & Hepatology. 2004 February; 16(2): 15762. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15075988
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Abnormal liver test results on routine screening. How to evaluate, when to refer for a biopsy. Author(s): Mallory MA, Lee SW, Kowdley KV. Source: Postgraduate Medicine. 2004 March; 115(3): 53-6, 59-62, 66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15038255
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Accuracy and clinical role of fine needle percutaneous biopsy with computerized tomography guidance of small (less than 4.0 cm) renal masses. Author(s): Neuzillet Y, Lechevallier E, Andre M, Daniel L, Coulange C. Source: The Journal of Urology. 2004 May; 171(5): 1802-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076280
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Alexia without agraphia following biopsy of a left thalamic tumor. Author(s): Tamhankar MA, Coslett HB, Fisher MJ, Sutton LN, Liu GT. Source: Pediatric Neurology. 2004 February; 30(2): 140-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984910
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An alternative clip-marking method for use after 14-gauge large core needle biopsy of the breast. Author(s): Gordon P. Source: Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes. 2004 April; 55(2): 75-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15131926
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An analysis of the p63/alpha-methylacyl coenzyme A racemase immunohistochemical cocktail stain in prostate needle biopsy specimens and tissue microarrays. Author(s): Sanderson SO, Sebo TJ, Murphy LM, Neumann R, Slezak J, Cheville JC. Source: American Journal of Clinical Pathology. 2004 February; 121(2): 220-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983935
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Anesthetic effect of intrauterine lidocaine plus naproxen sodium in endometrial biopsy. Author(s): Dogan E, Celiloglu M, Sarihan E, Demir A. Source: Obstetrics and Gynecology. 2004 February; 103(2): 347-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14754707
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Applying stereology to measure thickness of the basement membrane zone in bronchial biopsy specimens. Author(s): Ferrando RE, Nyengaard JR, Hays SR, Fahy JV, Woodruff PG. Source: The Journal of Allergy and Clinical Immunology. 2003 December; 112(6): 1243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657892
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Appropriate surgeon training for breast cancer sentinel lymph node biopsy. Author(s): McMasters KM. Source: American Journal of Surgery. 2003 September; 186(3): 313-4; Author Reply 314-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946840
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Assessing the validity of a model to identify patients for lymph node biopsy. Author(s): Tokuda Y, Kishaba Y, Kato J, Nakazato N. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2003 November; 82(6): 414-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663291
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Assessment of microvessel density in core needle biopsy specimen in breast cancer. Author(s): Ryden L, Boiesen P, Jonsson PE. Source: Anticancer Res. 2004 January-February; 24(1): 371-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15015623
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Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer. Author(s): Graefen M, Ohori M, Karakiewicz PI, Cagiannos I, Hammerer PG, Haese A, Erbersdobler A, Henke RP, Huland H, Wheeler TM, Slawin K, Scardino PT, Kattan MW. Source: The Journal of Urology. 2004 January; 171(1): 200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665876
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Benefits of the brush biopsy. Author(s): Curry JT. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 December; 61(12): 1506. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666939
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Biopsy assessment of drug efficacy in the gastrointestinal tract. Author(s): Walker MM. Source: British Journal of Clinical Pharmacology. 2003 November; 56(5): 483-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651720
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Biopsy needle technique and the accuracy of diagnosis of atypical ductal hyperplasia for mammographic abnormalities. Author(s): Zhao L, Freimanis R, Bergman S, Shen P, Perrier ND, Lesko N, Pulaski T, Pulaski S, Carr JJ, Levine EA. Source: The American Surgeon. 2003 September; 69(9): 757-62; Discussion 762. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509322
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Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Author(s): Qiu Y, Zhu J, Bandi V, Atmar RL, Hattotuwa K, Guntupalli KK, Jeffery PK. Source: American Journal of Respiratory and Critical Care Medicine. 2003 October 15; 168(8): 968-75. Epub 2003 July 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12857718
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Biopsy of focal liver lesions: guidelines, comparison of techniques and cost-analysis. Author(s): Francque SM, De Pauw FF, Van den Steen GH, Van Marck EA, Pelckmans PA, Michielsen PP. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 160-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891926
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Biopsy of sentinel node in mammary cancer: initial experience at the Centro Clinico de Estereotaxia, Caracas, Venezuela. Author(s): Acosta V, Contreras A, Ravelo R, Hurtado O, Marin E, Manso A, Perez J, Longobardi I. Source: The Breast Journal. 2003 November-December; 9(6): 509-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616951
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Biopsy of the conjunctiva in dry eye patients establishes a correlation between squamous metaplasia and dry eye clinical severity. Author(s): Murube J, Rivas L. Source: Eur J Ophthalmol. 2003 April; 13(3): 246-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747645
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Biopsy of the prostate--an ongoing evolution. Author(s): Macchia RJ. Source: The Journal of Urology. 2004 April; 171(4): 1487-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017204
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Biopsy specimens should be legally defined as donations. Author(s): Wright PK. Source: Bmj (Clinical Research Ed.). 2004 March 13; 328(7440): 642. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15016705
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Biopsy. Author(s): Shokar NK. Source: Family Medicine. 2003 September; 35(8): 550-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947516
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Biopsy-defined adult celiac disease in Asian-Canadians. Author(s): Freeman HJ. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 July; 17(7): 433-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915916
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Biopsy-proven alpha-glucosidase deficiency with normal lymphocyte enzyme activity. Author(s): Whitaker CH, Felice KJ, Natowicz M. Source: Muscle & Nerve. 2004 March; 29(3): 440-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981745
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Bisacodyl rectal preparation can decrease infectious complications of transrectal ultrasound-guided prostate biopsy. Author(s): Jeon SS, Woo SH, Hyun JH, Choi HY, Chai SE. Source: Urology. 2003 September; 62(3): 461-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946747
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Blind and ultrasound-guided percutaneous liver biopsy in children. Author(s): Nobili V, Comparcola D, Sartorelli MR, Natali G, Monti L, Falappa P, Marcellini M. Source: Pediatric Radiology. 2003 November; 33(11): 772-5. Epub 2003 September 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12961044
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Bone biopsy: indications, techniques, and complications. Author(s): Trueba D, Sawaya BP, Mawad H, Malluche HH. Source: Seminars in Dialysis. 2003 July-August; 16(4): 341-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926408
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Bone marrow biopsies for the diagnosis of systemic mastocytosis: is one biopsy sufficient? Author(s): Butterfield JH, Li CY. Source: American Journal of Clinical Pathology. 2004 February; 121(2): 264-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983941
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Bone marrow biopsy morbidity and mortality. Author(s): Bain BJ. Source: British Journal of Haematology. 2003 June; 121(6): 949-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786808
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Bone marrow biopsy related haemorrhage and low molecular weight heparin. Author(s): Morley NJ, Makris M. Source: British Journal of Haematology. 2003 November; 123(3): 562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617026
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Bone marrow core biopsy specimens in AL (primary) amyloidosis. A morphologic and immunohistochemical study of 100 cases. Author(s): Swan N, Skinner M, O'Hara CJ. Source: American Journal of Clinical Pathology. 2003 October; 120(4): 610-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560572
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Brain biopsy prior to treatment of Alzheimer's disease. Author(s): Holm A, Savolainen S, Alafuzoff I. Source: Minimally Invasive Neurosurgery : Min. 2003 June; 46(3): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872193
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Changing role of imaging-guided percutaneous biopsy of adrenal masses: evaluation of 50 adrenal biopsies. Author(s): Paulsen SD, Nghiem HV, Korobkin M, Caoili EM, Higgins EJ. Source: Ajr. American Journal of Roentgenology. 2004 April; 182(4): 1033-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15039183
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Characterization of prostate cancer missed by sextant biopsy. Author(s): Bak JB, Landas SK, Haas GP. Source: Clin Prostate Cancer. 2003 September; 2(2): 115-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040873
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Churg-Strauss vasculitis diagnosed on muscle biopsy. Author(s): Suresh E, Dhillon VB, Smith C, Ironside JW. Source: Journal of Clinical Pathology. 2004 March; 57(3): 334. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990615
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Clinical correlates to muscle biopsy findings in HIV patients experiencing fatigue: a case series. Author(s): Zell SC, Nielsen S. Source: J Int Assoc Physicians Aids Care (Chic Ill). 2002 Summer; 1(3): 90-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942681
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Clinical interpretation of the histological typing of gastric cancer using endoscopic forceps biopsy. Author(s): Matsubara Y, Yanai H, Ishiguro K, Ryozawa S, Okazaki Y, Matsui N, Okita K. Source: Hepatogastroenterology. 2004 January-February; 51(55): 285-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15011887
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Combined terminal ileoscopy and biopsy is superior to small bowel follow-through in detecting terminal ileal pathology. Author(s): Byrne MF, Power DG, Keeling AN, Kay E, Murray FE, Patchett SE. Source: Dig Liver Dis. 2004 February; 36(2): 147-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15002824
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Comparison of histologic grade between initial and follow-up biopsy in untreated, low to intermediate grade, localized prostate cancer. Author(s): Choo R, Do V, Sugar L, Klotz L, Bahk E, Hong E, Danjoux C, Morton G, DeBoer G. Source: Can J Urol. 2004 February; 11(1): 2118-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15003150
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Comparison of skin biopsy triage decisions in 49 patients with pigmented lesions and skin neoplasms: store-and-forward teledermatology vs face-to-face dermatology. Author(s): Shapiro M, James WD, Kessler R, Lazorik FC, Katz KA, Tam J, Nieves DS, Miller JJ. Source: Archives of Dermatology. 2004 May; 140(5): 525-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15148095
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Complication rate of transrectal ultrasound guided prostate biopsy: a comparison among 3 protocols with 6, 10 and 15 cores. Author(s): Berger AP, Gozzi C, Steiner H, Frauscher F, Varkarakis J, Rogatsch H, Bartsch G, Horninger W. Source: The Journal of Urology. 2004 April; 171(4): 1478-80; Discussion 1480-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017202
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Complications of bone marrow biopsy. Author(s): Marti J, Anton E, Valenti C. Source: British Journal of Haematology. 2004 February; 124(4): 557-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984509
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Contrast enhanced MR-guided biopsy of hepatocellular carcinoma. Author(s): Konig CW, Trubenbach J, Fritz J, Lauer UM, Claussen CD, Pereira PL. Source: Abdominal Imaging. 2004 January-February; 29(1): 71-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15160756
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Contrast-enhanced sonography as guidance for transthoracic biopsy of a peripheral lung lesion with large necrotic areas. Author(s): Sartori S, Nielsen I, Trevisani L, Tombesi P, Ceccotti P, Abbasciano V. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2004 January; 23(1): 133-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756362
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Core biopsy is accurate in determining the hormone receptor status of early breast cancer. Author(s): Harris K, Morafa I, Thomas V, Mokbel K. Source: American Journal of Surgery. 2004 April; 187(4): 568; Author Reply 568. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15041517
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Correlation of the primary Gleason pattern on prostate needle biopsy with clinicopathological factors in Gleason 7 tumors. Author(s): Grober ED, Tsihlias J, Jewett MA, Sweet JM, Evans AJ, Trachtenberg J, Robinette M, Nam RK. Source: Can J Urol. 2004 February; 11(1): 2157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15003158
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Craniospinal radiation in the treatment of biopsy-proven intracranial germinomas: twenty-five years' experience in a single center. Author(s): Maity A, Shu HK, Janss A, Belasco JB, Rorke L, Phillips PC, Sutton LN, Goldwein JW. Source: International Journal of Radiation Oncology, Biology, Physics. 2004 March 15; 58(4): 1165-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001260
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CT-guided needle biopsy of deep pelvic lesions by extraperitoneal approach through iliopsoas muscle. Author(s): Gupta S, Madoff DC, Ahrar K, Morello FA, Wallace MJ, Murthy R, Hicks ME. Source: Cardiovascular and Interventional Radiology. 2003 November-December; 26(6): 534-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061177
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CT-guided percutaneous needle biopsy in spine lesions. Author(s): Ozsarlak O, De Schepper AM, Wang X, De Raeve H. Source: Jbr-Btr. 2003 September-October; 86(5): 294-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651087
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CT-guided transbronchial biopsy using an ultrathin bronchoscope with virtual bronchoscopic navigation. Author(s): Shinagawa N, Yamazaki K, Onodera Y, Miyasaka K, Kikuchi E, Dosaka-Akita H, Nishimura M. Source: Chest. 2004 March; 125(3): 1138-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006979
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Current controversies in sentinel lymph node biopsy for breast cancer. Author(s): Allweis TM, Badriyyah M, Bar Ad V, Cohen T, Freund HR. Source: Breast (Edinburgh, Scotland). 2003 June; 12(3): 163-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659322
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Cytologic features and histologic correlations of microacinar and microtrabecular types of well-differentiated hepatocellular carcinoma in fine-needle aspiration biopsy. Author(s): Yang GC, Yang GY, Tao LC. Source: Cancer. 2004 February 25; 102(1): 27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14968415
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Dedifferentiated chondrosarcoma: use of MRI to guide needle biopsy. Author(s): Saifuddin A, Mann BS, Mahroof S, Pringle JA, Briggs TW, Cannon SR. Source: Clinical Radiology. 2004 March; 59(3): 268-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037140
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Detection of hepatitis C virus RNA in formalin-fixed, paraffin-embedded thin-needle liver biopsy specimens. Author(s): Vogt S, Schneider-Stock R, Klauck S, Roessner A, Rocken C. Source: American Journal of Clinical Pathology. 2003 October; 120(4): 536-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560564
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Detection of species-specific helicobacter ribosomal DNA in intestinal biopsy samples from a population-based cohort of patients with ulcerative colitis. Author(s): Streutker CJ, Bernstein CN, Chan VL, Riddell RH, Croitoru K. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 660-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766833
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Detection of Sporothrix schenckii chitin synthase 1 (CHS1) gene in biopsy specimens from human patients with sporotrichosis. Author(s): Kano R, Matsuoka A, Kashima M, Nakamura Y, Watanabe S, Mizoguchi M, Hasegawa A. Source: Journal of Dermatological Science. 2003 October; 33(1): 73-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527742
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Development of sentinel lymph node biopsy for melanoma. Author(s): Kelemen P. Source: Facial Plast Surg Clin North Am. 2003 February; 11(1): 69-74. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15062289
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Diagnosis of hepatocellular carcinoma (HCC) in a high-risk patient by using transgastric EUS-guided fine-needle biopsy (EUS-FNA). Author(s): Hollerbach S, Reiser M, Topalidis T, Konig M, Schmiegel W. Source: Zeitschrift Fur Gastroenterologie. 2003 October; 41(10): 995-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562197
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Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up. Author(s): Kirchhoff T, Merkesdal S, Rosenthal H, Prokop M, Chavan A, Wagner A, Mai U, Hammer M, Zeidler H, Galanski M. Source: European Radiology. 2003 October; 13(10): 2304-8. Epub 2003 March 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534805
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Diagnostic value of CT-guided biopsy of indeterminate renal masses. Author(s): Eshed I, Elias S, Sidi AA. Source: Clinical Radiology. 2004 March; 59(3): 262-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037139
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Diagnostic value of endobronchial ultrasound-guided transbronchial lung biopsy in peripheral lung cancers. Author(s): Yang MC, Liu WT, Wang CH, Lin HC, Chen HC, Chou CL, Hsueh S, Kuo HP. Source: J Formos Med Assoc. 2004 February; 103(2): 124-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15083243
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Differences in biopsy features between prostate cancers located in the transition and peripheral zone. Author(s): Augustin H, Erbersdobler A, Graefen M, Jaekel T, Haese A, Huland H, Hammerer PG. Source: Bju International. 2003 April; 91(6): 477-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656897
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Differential expression of cytokeratins 7 and 20 and thyroid transcription factor-1 in bronchioloalveolar carcinoma: an immunohistochemical study in fine-needle aspiration biopsy specimens. Author(s): Simsir A, Wei XJ, Yee H, Moreira A, Cangiarella J. Source: American Journal of Clinical Pathology. 2004 March; 121(3): 350-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023039
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Disseminated intravascular coagulation following transrectal ultrasound guided prostate biopsy. Author(s): Al-Otaibi MF, Al-Taweel W, Bin-Saleh S, Herba M, Aprikian AG. Source: The Journal of Urology. 2004 January; 171(1): 346. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665920
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Do unto others--why I would want anesthesia for my prostate biopsy. Author(s): Soloway MS. Source: Urology. 2003 December; 62(6): 973-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665338
Studies
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Does core needle breast biopsy accurately reflect breast pathology? Author(s): Crowe JP Jr, Rim A, Patrick RJ, Rybicki LA, Grundfest-Broniatowski SF, Kim JA, Lee KB. Source: Surgery. 2003 October; 134(4): 523-6; Discussion 526-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605609
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Does noninvasive staging of fibrosis challenge liver biopsy as a gold standard in chronic hepatitis C? Author(s): Berg T, Sarrazin C, Hinrichsen H, Buggisch P, Gerlach T, Zachoval R, Zeuzem S. Source: Hepatology (Baltimore, Md.). 2004 May; 39(5): 1456-7; Author Reply 1457-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15122779
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Does pericapsular lignocaine reduce pain during transrectal ultrasonography-guided biopsy of the prostate? Author(s): Manikandan R, Addla SK. Source: Bju International. 2003 April; 91(6): 584; Discussion 584. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656925
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Does pericapsular lignocaine reduce pain during transrectal ultrasonography-guided biopsy of the prostate? Author(s): Soloway MS. Source: Bju International. 2003 April; 91(6): 583-4; Discussion 584. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656924
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Does ultrasound core breast biopsy predict histologic finding on excisional biopsy? Author(s): Crowe JP Jr, Patrick RJ, Rybicki LA, Grundfest SF, Kim JA, Lee KB, Rim A. Source: American Journal of Surgery. 2003 October; 186(4): 397-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14553858
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Dye-guided sentinel node biopsy revisited; validation and observational study from a single institute. Author(s): Aihara T, Takatsuka Y. Source: Breast Cancer. 2003; 10(3): 254-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955039
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Dynamics of human papillomavirus infection between biopsy and excision of cervical intraepithelial neoplasia: results from the ZYC101a protocol. Author(s): Crum CP, Beach KJ, Hedley ML, Yuan L, Lee KR, Wright TC, Urban RG. Source: The Journal of Infectious Diseases. 2004 April 15; 189(8): 1348-54. Epub 2004 March 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15073670
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Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease. Author(s): Moskowitz CH, Kewalramani T, Nimer SD, Gonzalez M, Zelenetz AD, Yahalom J. Source: British Journal of Haematology. 2004 March; 124(5): 645-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14871252
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Efficacy of bronchial wash cytology and its correlation with biopsy in lung tumours. Author(s): Ahmad M, Afzal S, Saeed W, Mubarik A, Saleem N, Khan SA, Rafi S. Source: J Pak Med Assoc. 2004 January; 54(1): 13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15058635
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Efficacy of sentinel lymph node biopsy in male breast cancer. Author(s): Cimmino VM, Degnim AC, Sabel MS, Diehl KM, Newman LA, Chang AE. Source: Journal of Surgical Oncology. 2004 May 1; 86(2): 74-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15112248
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Emergence of sentinel node biopsy in breast cancer as standard-of-care in academic comprehensive cancer centers. Author(s): Edge SB, Niland JC, Bookman MA, Theriault RL, Ottesen R, Lepisto E, Weeks JC. Source: Journal of the National Cancer Institute. 2003 October 15; 95(20): 1514-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559873
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Endometrial biopsy and improved conception and implantation. Author(s): Ansbacher R. Source: Fertility and Sterility. 2003 November; 80(5): 1288-9; Author Reply 1289. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607599
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Endorectal magnetic resonance imaging and spectroscopy for the detection of tumor foci in men with prior negative transrectal ultrasound prostate biopsy. Author(s): Yuen JS, Thng CH, Tan PH, Khin LW, Phee SJ, Xiao D, Lau WK, Ng WS, Cheng CW. Source: The Journal of Urology. 2004 April; 171(4): 1482-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017203
Studies
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Endoscopic transesophageal and endoscopic transbronchial real-time ultrasoundguided biopsy. Author(s): Krasnik M. Source: Respiration; International Review of Thoracic Diseases. 2003 May-June; 70(3): 293-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915749
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Endoscopic ultrasonography and endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of lower digestive tract disease. Author(s): Hara K, Yamao K, Ohashi K, Nakamura T, Suzuki T, Sawaki A, Matsumoto K, Okubo K, Tanaka K, Moriyama I, Matsueda K, Kosikawa T, Ueyama U, Yokoi T. Source: Endoscopy. 2003 November; 35(11): 966-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606022
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Endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of pancreatic masses. Author(s): Jinga M, Gheorghe C, Dumitrescu M, Gheorghe L, Nicolaie T. Source: Rom J Gastroenterol. 2004 March; 13(1): 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15054527
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Endoscopic ultrasound-guided fine needle aspiration biopsy of suspected cholangiocarcinoma. Author(s): Eloubeidi MA, Chen VK, Jhala NC, Eltoum IE, Jhala D, Chhieng DC, Syed SA, Vickers SM, Mel Wilcox C. Source: Clin Gastroenterol Hepatol. 2004 March; 2(3): 209-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017604
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Endoscopic ultrasound-guided fine-needle aspiration biopsy of liver lesions: histological and cytological assessment. Author(s): Hollerbach S, Willert J, Topalidis T, Reiser M, Schmiegel W. Source: Endoscopy. 2003 September; 35(9): 743-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12929021
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Endothelial nitric oxide synthase haplotype associations in biopsy-proven giant cell arteritis. Author(s): Amoli MM, Garcia-Porrua C, Llorca J, Ollier WE, Gonzalez-Gay MA. Source: The Journal of Rheumatology. 2003 September; 30(9): 2019-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12966609
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Entonox analgesia for prostatic biopsy. Author(s): McIntyre IG, Dixon A, Pantelides ML. Source: Prostate Cancer and Prostatic Diseases. 2003; 6(3): 235-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970727
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Epididymitis after transrectal ultrasound-guided needle biopsy of prostate gland. Author(s): Donzella JG, Merrick GS, Lindert DJ, Andreini HJ Jr, Curtis RL, Luna IH, Allen Z, Butler WM. Source: Urology. 2004 February; 63(2): 306-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14972477
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EUS-guided trucut biopsy for diagnosis of an esophageal stromal tumor: case report. Author(s): Yadav D, Levy MJ, Schwartz D, Jondal ML, Clain J, Wiersema MJ. Source: Gastrointestinal Endoscopy. 2003 September; 58(3): 457-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528231
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Evaluation of a new biopsy urease test: Pronto Dry, for the diagnosis of Helicobacter pylori infection. Author(s): Said RM, Cheah PL, Chin SC, Goh KL. Source: European Journal of Gastroenterology & Hepatology. 2004 February; 16(2): 1959. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15075994
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Evaluation of Breast Imaging Reporting and Data System Category 3 mammograms and the use of stereotactic vacuum-assisted breast biopsy in a nonacademic community practice. Author(s): Mendez A, Cabanillas F, Echenique M, Malekshamran K, Perez I, Ramos E. Source: Cancer. 2004 February 15; 100(4): 710-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14770425
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Evaluation of core needle biopsy as a substitute to open biopsy in the diagnosis of soft-tissue masses. Author(s): Ray-Coquard I, Ranchere-Vince D, Thiesse P, Ghesquieres H, Biron P, Sunyach MP, Rivoire M, Lancry L, Meeus P, Sebban C, Blay JY. Source: European Journal of Cancer (Oxford, England : 1990). 2003 September; 39(14): 2021-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957456
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Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy (B4) or lesion of uncertain malignant potential (B3). Author(s): Lee AH, Denley HE, Pinder SE, Ellis IO, Elston CW, Vujovic P, Macmillan RD, Evans AJ; Nottingham Breast Team. Source: Histopathology. 2003 April; 42(4): 331-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653944
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Extra-axillary sentinel node biopsy in breast cancer staging--is it necessary? Author(s): Victorzon M, Hamalainen E, Svartback M, Lantto A. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 September; 29(7): 604-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943627
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False glomerulus in renal biopsy specimen: a possible pitfall under the dissecting microscope. Author(s): Hattori H. Source: Journal of Clinical Pathology. 2004 March; 57(3): 336. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990617
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False-negative frozen section of sentinel lymph node biopsy for breast cancer. Author(s): Holck S, Galatius H, Engel U, Wagner F, Hoffmann J. Source: Breast (Edinburgh, Scotland). 2004 February; 13(1): 42-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759715
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Fast and accurate quantitative detection of Helicobacter pylori and identification of clarithromycin resistance mutations in H. pylori isolates from gastric biopsy specimens by real-time PCR. Author(s): Lascols C, Lamarque D, Costa JM, Copie-Bergman C, Le Glaunec JM, Deforges L, Soussy CJ, Petit JC, Delchier JC, Tankovic J. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4573-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532184
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Fast MRI-guided vacuum-assisted breast biopsy: initial experience. Author(s): Liberman L, Morris EA, Dershaw DD, Thornton CM, Van Zee KJ, Tan LK. Source: Ajr. American Journal of Roentgenology. 2003 November; 181(5): 1283-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573421
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Feasibility of sentinel node biopsy for breast cancer after neoadjuvant endocrine therapy: a pilot study. Author(s): Aihara T, Munakata S, Morino H, Takatsuka Y. Source: Journal of Surgical Oncology. 2004 February; 85(2): 77-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755507
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Fibrin-glue sealed liver biopsy in patients with a liver transplantation or in liver transplantation waiting list: preliminary results. Author(s): Albeniz Arbizu E, Lopez San Roman A, Garcia Gonzalez M, Foruny Olcina JR, Garcia-Hoz Rosales F, Barcena Marugan R, Plaza Palacios G, Gil Grande LA. Source: Transplantation Proceedings. 2003 August; 35(5): 1911-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962845
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Fine needle aspiration biopsy of gastric duplication cysts with endoscopic ultrasound guidance. Author(s): Ponder TB, Collins BT. Source: Acta Cytol. 2003 July-August; 47(4): 571-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920748
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Fine needle aspiration biopsy of precursor B-cell lymphoblastic lymphoma presenting as a sacral mass. A case report. Author(s): Ezenekwe AM, Collins BT, Ponder TB. Source: Acta Cytol. 2004 March-April; 48(2): 239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085760
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Fine needle aspiration biopsy of primary renal synovial sarcoma. A case report. Author(s): Vesoulis Z, Rahmeh T, Nelson R, Clarke R, Lu Y, Dankoff J. Source: Acta Cytol. 2003 July-August; 47(4): 668-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920764
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Fine needle aspiration biopsy of the parotid gland. Diagnostic problems and 2 uncommon cases. Author(s): Behzatoglu K, Bahadir B, Kaplan HH, Yucel Z, Durak H, Bozkurt ER. Source: Acta Cytol. 2004 March-April; 48(2): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085745
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Fine needle aspiration biopsy of vertebral lesions. Author(s): Saad RS, Clary KM, Liu Y, Silverman JF, Raab SS. Source: Acta Cytol. 2004 January-February; 48(1): 39-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969179
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Fine needle biopsy of focal liver lesions: the hepatologist's point of view. Author(s): Caturelli E, Ghittoni G, Roselli P, De Palo M, Anti M. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2004 February; 10(2 Suppl 1): S26-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762835
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Fine-needle aspiration biopsy and intraoperative cytologic smear findings in a case of benign mesothelial-cell inclusions involving a lymph node: case report and review of the literature. Author(s): Paull G, Mosunjac M. Source: Diagnostic Cytopathology. 2003 September; 29(3): 163-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951686
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Fine-needle aspiration biopsy of the central nervous system performed freehand under computed tomography guidance without stereotactic instrumentation. Author(s): Seliem RM, Assaad MW, Gorombey SJ, Moral LA, Kirkwood JR, Otis CN. Source: Cancer. 2003 October 25; 99(5): 277-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14579294
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Fine-needle aspiration cytology, frozen section, and open biopsy: relative significance in diagnosis of musculoskeletal tumors. Author(s): Shah MS, Garg V, Kapoor SK, Dhaon BK, Gondal R. Source: J Surg Orthop Adv. 2003 Winter; 12(4): 203-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008283
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Five years of sentinel node biopsy for melanoma: the St George's Melanoma Unit experience. Author(s): Topping A, Dewar D, Rose V, Cavale N, Allen R, Cook M, Powell B. Source: British Journal of Plastic Surgery. 2004 March; 57(2): 97-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037163
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Flow cytometry in the diagnosis of lymphoproliferative lesions of the orbit and eye adnexa in fine needle aspiration biopsy. Author(s): Wolska-Szmidt E, Masiuk M, Krzystolik K, Chosia M. Source: Pol J Pathol. 2003; 54(4): 253-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998294
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Flow-cytometric diagnosis of thymoma using needle biopsy specimens. Author(s): Yokoyama T, Tanahashi M, Tateyama H, Yamakawa Y, Kiriyama M, Fujii Y. Source: Surgery Today. 2003; 33(3): 163-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658380
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Follow-up by combined cytology and human papillomavirus testing for patients postcone biopsy: results of a long-term follow-up. Author(s): Bar-Am A, Gamzu R, Levin I, Fainaru O, Niv J, Almog B. Source: Gynecologic Oncology. 2003 October; 91(1): 149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529675
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Fourteen-gauge needle core biopsy of mammographically evident radial scars: is excision necessary? Author(s): Brodie C, O'Doherty A, Quinn C. Source: Cancer. 2004 February 1; 100(3): 652-3; Author Reply 653-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745884
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Gastral antral biopsy in the differentiation of pediatric colitides. Author(s): Kundhal PS, Stormon MO, Zachos M, Critch JN, Cutz E, Griffiths AM. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 557-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650787
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Gastric biopsy-based rapid urease tests for the detection of Helicobacter pylori: progress, advantages and limitations. Author(s): Xia HH, Wong BC. Source: Journal of Gastroenterology and Hepatology. 2002 June; 17(6): 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100605
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Gastric intestinal metaplasia on routine endoscopic biopsy. Author(s): Fennerty MB. Source: Gastroenterology. 2003 August; 125(2): 586-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891560
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Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy-proven Stage IIIA(N2) nonsmall cell lung carcinoma: a Phase II multicenter study. Author(s): De Marinis F, Nelli F, Migliorino MR, Martelli O, Cortesi E, Treggiari S, Portalone L, Crispino C, Brancaccio L, Gridelli C. Source: Cancer. 2003 October 15; 98(8): 1707-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534888
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General practitioners' greater choice for sentinel node biopsy than patients in the UK. Author(s): Pereira B, Tamer M, Khalifa K, Mokbel K. Source: Current Medical Research and Opinion. 2004 March; 20(3): 417. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025851
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Genotyping of Helicobacter pylori in paraffin-embedded gastric biopsy specimens: relation to histological parameters and effects on therapy. Author(s): Scholte GH, van Doorn LJ, Cats A, Bloemena E, Lindeman J, Quint WG, Meuwissen SG, Kuipers EJ. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1687-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135019
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Gleason score on biopsy: is it reliable for predicting the final grade on pathology? Author(s): Lattouf JB, Saad F. Source: Bju International. 2002 November; 90(7): 694-8; Discussion 698-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12410749
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Gleason scores of prostate biopsy and radical prostatectomy specimens over the past 10 years: is there evidence for systematic upgrading? Author(s): Smith EB, Frierson HF Jr, Mills SE, Boyd JC, Theodorescu D. Source: Cancer. 2002 April 15; 94(8): 2282-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12001128
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Gluteal compartment syndrome and sciatica after bone marrow biopsy: a case report and review of the literature. Author(s): Roth JS, Newman EC. Source: The American Surgeon. 2002 September; 68(9): 791-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356152
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Granulomatous mastitis diagnosed by core-needle biopsy and successfully treated with corticosteroid therapy: a case report. Author(s): Hirata S, Saito T, Kiyanagi K, Kitada M, Yamazaki K, Sasajima T, Ohsaki Y, Miyokawa N. Source: Breast Cancer. 2003; 10(4): 378-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14634520
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Guidelines for radiologically guided lung biopsy. Author(s): Manhire A, Charig M, Clelland C, Gleeson F, Miller R, Moss H, Pointon K, Richardson C, Sawicka E; BTS. Source: Thorax. 2003 November; 58(11): 920-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586042
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Guidewire technique for endoscopic transpapillary procurement of bile duct biopsy specimens without endoscopic sphincterotomy. Author(s): Lin LF, Siauw CP, Ho KS, Tung JN. Source: Gastrointestinal Endoscopy. 2003 August; 58(2): 272-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872103
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Haematochezia in Crohn's disease caused by late-onset haemobilia following percutaneous liver biopsy. Author(s): Hodgson RS, Taylor-Robinson SD, Jackson JE. Source: European Journal of Gastroenterology & Hepatology. 2004 February; 16(2): 22932. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076000
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Heart and liver disease in 32 patients undergoing biopsy of both organs, with implications for heart or liver transplantation. Author(s): Ocel JJ, Edwards WD, Tazelaar HD, Petrovic LM, Edwards BS, Kamath PS. Source: Mayo Clinic Proceedings. 2004 April; 79(4): 492-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15065614
92
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Heat shock protein 70 (Hsp70) membrane expression on head-and-neck cancer biopsy-a target for natural killer (NK) cells. Author(s): Kleinjung T, Arndt O, Feldmann HJ, Bockmuhl U, Gehrmann M, Zilch T, Pfister K, Schonberger J, Marienhagen J, Eilles C, Rossbacher L, Multhoff G. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 November 1; 57(3): 820-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529789
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Heat shock proteins are present in mallory bodies (cytokeratin aggresomes) in human liver biopsy specimens. Author(s): Riley NE, Li J, McPhaul LW, Bardag-Gorce F, Lue YH, French SW. Source: Experimental and Molecular Pathology. 2003 April; 74(2): 168-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12710948
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Hemodynamically relevant hematuria several months after biopsy of a kidney graft: an unusual cause. Author(s): Voiculescu A, Brause M, Engelbrecht V, Sandmann W, Pfeiffer T, Grabensee B. Source: Clinical Nephrology. 2003 March; 59(3): 217-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653267
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Hepatocellular nodules in cirrhosis: focus on diagnostic criteria on liver biopsy. A Western experience. Author(s): Roncalli M. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2004 February; 10(2 Suppl 1): S9-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762832
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Hepatoma in a young adult: to biopsy or not to biopsy? Author(s): Brenner C, Amin Z, Wotherspoon AC, Vlavianos P, Andreyev J. Source: Gut. 2003 June; 52(6): 905-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740352
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Hertig and beyond: a systematic and practical approach to the endometrial biopsy. Author(s): Crum CP, Hornstein MD, Nucci MR, Mutter GL. Source: Advances in Anatomic Pathology. 2003 November; 10(6): 301-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581820
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Heterogeneity of cag genotypes in Helicobacter pylori isolates from human biopsy specimens. Author(s): Tomasini ML, Zanussi S, Sozzi M, Tedeschi R, Basaglia G, De Paoli P. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 976-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624018
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High degree of mitochondrial 3243 mutation in gastric biopsy specimen in a patient with MELAS and diabetes complicated by marked gastrointestinal abnormalities. Author(s): Inoue K, Ikegami H, Fujisawa T, Kawabata Y, Shintani M, Nijima K, Masaya O, Nishino M, Itoi-Babaya M, Babaya N, Ogihara T. Source: Diabetes Care. 2003 July; 26(7): 2219. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832349
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High diagnostic accuracy of adrenal core biopsy: results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients. Author(s): Saeger W, Fassnacht M, Chita R, Prager G, Nies C, Lorenz K, Barlehner E, Simon D, Niederle B, Beuschlein F, Allolio B, Reincke M. Source: Human Pathology. 2003 February; 34(2): 180-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612887
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High-grade prostatic intraepithelial neoplasia on needle biopsy: risk of cancer on repeat biopsy related to number of involved cores and morphologic pattern. Author(s): Bishara T, Ramnani DM, Epstein JI. Source: The American Journal of Surgical Pathology. 2004 May; 28(5): 629-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15105651
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Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy? Author(s): Wee A, Nilsson B. Source: Acta Cytol. 2003 January-February; 47(1): 16-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12585026
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Histopathologic changes in parotid gland parenchyma after fine needle aspiration biopsy of a Warthin's tumour. A case report. Author(s): Starek I, Skalova A, Tichy T. Source: Pathology, Research and Practice. 2002; 198(12): 829-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608661
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Histopathological diagnosis of biopsy samples from early esophageal carcinoma. Author(s): Meneses-Garcia A, Kumagai J, Takizawa T, Koike M, Kawano T. Source: J Exp Clin Cancer Res. 2002 December; 21(4): 621-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636112
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How I do it--biopsy of axillary and internal mammary sentinel node for complete nodal staging in male breast cancer. Author(s): Gennari R, Ballardini B, Costa A. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2002 August; 28(5): 557-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12217311
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How many cases are enough for accreditation in sentinel lymph node biopsy in breast cancer? Author(s): Sanidas EE, de Bree E, Tsiftsis DD. Source: American Journal of Surgery. 2003 March; 185(3): 202-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620556
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How often does alpha-methylacyl-CoA-racemase contribute to resolving an atypical diagnosis on prostate needle biopsy beyond that provided by basal cell markers? Author(s): Zhou M, Aydin H, Kanane H, Epstein JI. Source: The American Journal of Surgical Pathology. 2004 February; 28(2): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15043314
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How to improve the specificity and sensitivity of biopsy technique in screening. Author(s): Ciatto S, Vis A, Finne P. Source: Bju International. 2003 December; 92 Suppl 2: 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983961
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Human papilloma virus testing in patient follow-up post cone biopsy due to highgrade cervical intraepithelial neoplasia. Author(s): Almog B, Gamzu R, Kuperminc MJ, Levin I, Fainaru O, Niv J, Bar-Am A. Source: Gynecologic Oncology. 2003 March; 88(3): 345-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648585
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IgA antibodies against tissue transglutaminase in the diagnosis of celiac disease: concordance with intestinal biopsy in children and adults. Author(s): Llorente MJ, Sebastian M, Fernandez-Acenero MJ, Prieto G, Villanueva S. Source: Clinical Chemistry. 2004 February; 50(2): 451-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752021
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Imaging-guided percutaneous splenic biopsy using a 20- or 22-gauge cutting-edge core biopsy needle for the diagnosis of malignant lymphoma. Author(s): Lieberman S, Libson E, Maly B, Lebensart P, Ben-Yehuda D, Bloom AI. Source: Ajr. American Journal of Roentgenology. 2003 October; 181(4): 1025-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500223
Studies
95
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Immunohistochemical analysis of adhesion molecule expression on muscle biopsy specimens from patients with juvenile dermatomyositis. Author(s): Sallum AM, Marie SK, Wakamatsu A, Sachetti S, Vianna MA, Silva CA, Kiss MH. Source: The Journal of Rheumatology. 2004 April; 31(4): 801-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15088312
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Impact of endoscopic ultrasound combined with fine-needle aspiration biopsy in the management of esophageal cancer. Author(s): Chang KJ, Soetikno RM, Bastas D, Tu C, Nguyen PT. Source: Endoscopy. 2003 November; 35(11): 962-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606021
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Importance of kidney biopsy in graft selection. Author(s): Vazquez Martul E, Veiga Barreiro A. Source: Transplantation Proceedings. 2003 August; 35(5): 1658-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962746
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Improved detection of clinically significant, curable prostate cancer with systematic 12-core biopsy. Author(s): Singh H, Canto EI, Shariat SF, Kadmon D, Miles BJ, Wheeler TM, Slawin KM. Source: The Journal of Urology. 2004 March; 171(3): 1089-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767277
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Inadvertent myocardial biopsy by a trapped Seldinger wire. Author(s): Harding J, Nevin M. Source: Anaesthesia. 2004 February; 59(2): 194-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14725531
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Indication and contraindication for hepatic resection for liver tumors without fineneedle biopsy: validation and extension of an Eastern approach in a Western community hospital. Author(s): Torzilli G, Olivari N, Del Fabbro D, Leoni P, Gendarini A, Palmisano A, Montorsi M, Makuuchi M. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2004 February; 10(2 Suppl 1): S30-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762836
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Initiation of glucocorticoid therapy: before or after temporal artery biopsy? Author(s): Younge BR, Cook BE Jr, Bartley GB, Hodge DO, Hunder GG. Source: Mayo Clinic Proceedings. 2004 April; 79(4): 483-91. Erratum In: Mayo Clin Proc. 2004 May; 79(5): 709. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15065613
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Interdisciplinary consensus on the use and technique of vacuum-assisted stereotactic breast biopsy. Author(s): Heywang-Kobrunner SH, Schreer I, Decker T, Bocker W. Source: European Journal of Radiology. 2003 September; 47(3): 232-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927668
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Intermittent-mode CT fluoroscopy-guided biopsy of the lung or upper abdomen with breath-hold monitoring and feedback: system development and feasibility. Author(s): Carlson SK, Felmlee JP, Bender CE, Ehman RL, Classic KL, Hu HH, Hoskin TL. Source: Radiology. 2003 December; 229(3): 906-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657321
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Intracellular signalling molecules as immunohistochemical markers of normal and neoplastic human leucocytes in routine biopsy samples. Author(s): Pozzobon M, Marafioti T, Hansmann ML, Natkunam Y, Mason DY. Source: British Journal of Haematology. 2004 February; 124(4): 519-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984504
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Intranodal myofibroblastoma: DNA image cytometry on aspiration biopsy material. Author(s): Ferrara G, Nigro M, Verrioli M. Source: Diagnostic Cytopathology. 2003 September; 29(3): 179-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951689
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Intraoperative ultrasonographically guided excisional biopsy or vacuum-assisted core needle biopsy for nonpalpable breast lesions. Author(s): Chen SC, Yang HR, Hwang TL, Chen MF, Cheung YC, Hsueh S. Source: Annals of Surgery. 2003 November; 238(5): 738-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578737
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Intratumor microvessel density in biopsy specimens predicts local response of hypopharyngeal cancer to radiotherapy. Author(s): Zhang SC, Miyamoto S, Kamijo T, Hayashi R, Hasebe T, Ishii G, Fukayama M, Ochiai A. Source: Japanese Journal of Clinical Oncology. 2003 December; 33(12): 613-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769838
Studies
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Is completion lymphadenectomy after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary? Author(s): Elias N, Tanabe KK, Sober AJ, Gadd MA, Mihm MC, Goodspeed B, Cosimi AB. Source: Archives of Surgery (Chicago, Ill. : 1960). 2004 April; 139(4): 400-4; Discussion 404-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078708
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Is it necessary to perform prospective randomized studies before sentinel node biopsy can replace routine axillary dissection? Author(s): Noguchi M. Source: Breast Cancer. 2003; 10(3): 179-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955029
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Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma (EJSO 2002; 28: 673--678). Author(s): Trost O, Danino AM, Dutronc Y, Dalac S, Lambert D, Malka G. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 October; 29(8): 699. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511622
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Is there a role for sentinel lymph node biopsy in the management of sarcoma? Author(s): Blazer DG 3rd, Sabel MS, Sondak VK. Source: Surgical Oncology. 2003 November; 12(3): 201-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957624
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Isolated supraclavicular lymph node recurrence after breast-conserving surgery and negative axillary sentinel node biopsy. Author(s): Agnese DM, Williams J, Burak WE Jr. Source: The Breast Journal. 2003 November-December; 9(6): 501-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616947
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Junior doctors' experience of percutaneous liver biopsy: a questionnaire survey. Author(s): Haniffa MA, Kumaran S, Tamin SS, Alexander GJ. Source: Clinical Medicine (London, England). 2002 July-August; 2(4): 379-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195871
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K-ras gene mutation in the diagnosis of ultrasound guided fine-needle biopsy of pancreatic masses. Author(s): Zheng M, Liu LX, Zhu AL, Qi SY, Jiang HC, Xiao ZY. Source: World Journal of Gastroenterology : Wjg. 2003 January; 9(1): 188-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508380
98
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Lack of association between ICAM-1 gene polymorphisms and biopsy-proven erythema nodosum. Author(s): Amoli MM, Ollier WE, Lueiro M, Fernandez ML, Garcia-Porrua C, GonzalezGay MA. Source: The Journal of Rheumatology. 2004 February; 31(2): 403-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760823
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Laparoscopic liver biopsy performed safely in a child with hepatic dysfunction: report of a case. Author(s): Kimura T, Nakajima K, Wasa M, Hasegawa T, Soh H, Mushiake S, Okada A. Source: Surgery Today. 2003; 33(9): 712-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928853
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Laparoscopic renal biopsy: a 9-year experience. Author(s): Shetye KR, Kavoussi LR, Ramakumar S, Fugita OE, Jarrett TW. Source: Bju International. 2003 June; 91(9): 817-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780840
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Laparoscopic ultrasonography and biopsy of hepatic tumors in 310 patients. Author(s): Berber E, Garland AM, Engle KL, Rogers SJ, Siperstein AE. Source: American Journal of Surgery. 2004 February; 187(2): 213-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769307
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Laparoscopy and guided liver biopsy in the diagnosis of cirrhosis: conventional technique vs. minilaparoscopy. Author(s): Orlando R, Lirussi F. Source: Endoscopy. 2003 December; 35(12): 1079-80; Author Reply 1080. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648425
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Large-gauge needle biopsy in diagnosing malignant breast neoplasia. Author(s): Fures R, Bukovic D, Lez C, Zadro M, Bukovic N, Smud D, Giudici E. Source: Coll Antropol. 2003 June; 27(1): 259-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974154
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Laser-assisted human embryo biopsy on the third day of development for preimplantation genetic diagnosis: two successful case reports. Author(s): Han TS, Sagoskin AW, Graham JR, Tucker MJ, Liebermann J. Source: Fertility and Sterility. 2003 August; 80(2): 453-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909515
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Leiomyosarcoma of the breast: a difficult diagnosis on fine-needle aspiration biopsy. Author(s): Jun Wei X, Hiotis K, Garcia R, Hummel Levine P. Source: Diagnostic Cytopathology. 2003 September; 29(3): 172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951688
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Lidocaine iontophoresis for local anesthesia before shave biopsy. Author(s): Zempsky WT, Parkinson TM. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 June; 29(6): 627-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786707
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Liver biopsy in co-infected patients. Author(s): Santos J, Palacios R. Source: Aids (London, England). 2004 January 23; 18(2): 354. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15075565
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Liver biopsy size matters in chronic hepatitis: bigger is better. Author(s): Scheuer PJ. Source: Hepatology (Baltimore, Md.). 2003 December; 38(6): 1356-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14647044
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Longitudinal nail biopsy: utility in 20-nail dystrophy. Author(s): Grover C, Khandpur S, Reddy BS, Chaturvedi KU. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 November; 29(11): 1125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641339
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Loss of expression of the putative tumor suppressor NES1 gene in biopsy-proven ductal carcinoma in situ predicts for invasive carcinoma at definitive surgery. Author(s): Yunes MJ, Neuschatz AC, Bornstein LE, Naber SP, Band V, Wazer DE. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 July 1; 56(3): 653-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788170
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Low AUA symptom score independently predicts positive prostate needle biopsy: results from a racially diverse series of 411 patients. Author(s): Porter CR, Kim J. Source: Urology. 2004 January; 63(1): 90-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751356
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Lung biopsy guidelines--for the obedience of fools and guidance of wise men. Author(s): Manhire AR, Richardson CM, Gleeson FV. Source: Thorax. 2003 November; 58(11): 913-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586037
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Lymph node status and survival in cutaneous malignant melanoma--sentinel lymph node biopsy impact. Author(s): Rutkowski P, Nowecki ZI, Nasierowska-Guttmejer A, Ruka W. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 September; 29(7): 611-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943629
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Lymphatic mapping and sentinel node biopsy during laparoscopic gastrectomy for early cancer. Author(s): Tonouchi H, Mohri Y, Tanaka K, Konishi N, Ohmori Y, Kobayashi M, Watanabe Y, Matsumura K, Takeda K, Kusunoki M. Source: Digestive Surgery. 2003; 20(5): 421-7. Epub 2003 July 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900533
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Lymphatic mapping and sentinel node biopsy in gastric cancer. Author(s): Song X, Wang L, Chen W, Pan T, Zhu H, Xu J, Jin M, Finley RK 3rd, Wu J. Source: American Journal of Surgery. 2004 February; 187(2): 270-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769318
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Lymphatic mapping and sentinel node biopsy using 99mTc tin colloid in gastric cancer. Author(s): Kim MC, Kim HH, Jung GJ, Lee JH, Choi SR, Kang DY, Roh MS, Jeong JS. Source: Annals of Surgery. 2004 March; 239(3): 383-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15075656
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Lymphomas diagnosed by percutaneous kidney biopsy. Author(s): Tornroth T, Heiro M, Marcussen N, Franssila K. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 November; 42(5): 960-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582040
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Mammary lesions diagnosed as "papillary" by aspiration biopsy: 70 cases with follow-up. Author(s): Simsir A, Waisman J, Thorner K, Cangiarella J. Source: Cancer. 2003 June 25; 99(3): 156-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811856
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Management of cervical intraepithelial neoplasia: the role of biopsy. Author(s): Fambrini M, Penna C, Fallani MG, Marchionni M. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 August; 82(2): 219-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873786
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Management of clinically node negative penile carcinoma: improved survival after the introduction of dynamic sentinel node biopsy. Author(s): Lont AP, Horenblas S, Tanis PJ, Gallee MP, van Tinteren H, Nieweg OE. Source: The Journal of Urology. 2003 September; 170(3): 783-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913697
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Massive bleeding from an arteriovenous malformation in the gastric fundus following gastric biopsy treated by embolisation. Author(s): Ibrahim AS, Allangawi MH, al-Muzrakchi AM. Source: Int J Clin Pract. 2003 May; 57(4): 354-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12800475
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Metastatic lobular breast carcinoma to an endometrial polyp diagnosed by hysteroscopic biopsy. Author(s): Alvarez C, Ortiz-Rey JA, Estevez F, de la Fuente A. Source: Obstetrics and Gynecology. 2003 November; 102(5 Pt 2): 1149-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607038
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Metastatic pattern and survival in disseminated conjunctival melanoma: implications for sentinel lymph node biopsy. Author(s): Tuomaala S, Kivela T. Source: Ophthalmology. 2004 April; 111(4): 816-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15051218
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Morphologic criteria using biopsy specimens to define the risk of gastric cancer in patients with Helicobacter pylori infection. Author(s): Fukuda S, Tanaka M, Shimoyama T, Sawaya M, Nakaji S, Munakata A. Source: Japanese Journal of Clinical Oncology. 2003 August; 33(8): 396-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523059
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Morphometric classification of hairy cell leukemia in bone marrow trephine biopsy. Author(s): Okon K, Szumera A, Papla B, Pietkun I, Zdunczyk A, Rucinska M, Skotnicki AB, Stachura J. Source: Anal Quant Cytol Histol. 2003 August; 25(4): 227-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12961830
102
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MR fluoroscopy-guided transthoracic fine-needle aspiration biopsy: feasibility. Author(s): Sakarya ME, Unal O, Ozbay B, Uzun K, Kati I, Ozen S, Etlik O. Source: Radiology. 2003 August; 228(2): 589-92. Epub 2003 June 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819336
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MR imaging-guided breast biopsy using a coaxial technique with a 14-gauge stainless steel core biopsy needle and a titanium sheath. Author(s): Lehman CD, Eby PR, Chen X, Dee KE, Thursten B, McCloskey J. Source: Ajr. American Journal of Roentgenology. 2003 July; 181(1): 183-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818854
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MRI-guided breast biopsy: clinical experience with 14-gauge stainless steel core biopsy needle. Author(s): Chen X, Lehman CD, Dee KE. Source: Ajr. American Journal of Roentgenology. 2004 April; 182(4): 1075-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15039191
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Multifocality and sentinel node biopsy in breast cancer. Author(s): Goyal A, Mansel RE. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2004 February; 30(1): 3-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736514
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Multiple measures of carcinoma extent versus perineural invasion in prostate needle biopsy tissue in prediction of pathologic stage in a screening population. Author(s): Bismar TA, Lewis JS Jr, Vollmer RT, Humphrey PA. Source: The American Journal of Surgical Pathology. 2003 April; 27(4): 432-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657927
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Muscle biopsy for malignant hyperthermia testing can be scheduled and performed in 6 weeks. Author(s): Rosenbaum HK. Source: Anesthesia and Analgesia. 2003 November; 97(5): 1549; Author Reply 1549. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570697
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Muscle biopsy investigations on neuromuscular insufficiency of the rotator cuff: a contribution to the functional impingement of the shoulder joint. Author(s): Irlenbusch U, Gansen HK. Source: Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons. [et Al.]. 2003 September-October; 12(5): 422-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564260
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Necessity of endometrial biopsy in women with enlarged uteri and a preoperative diagnosis of uterine leiomyomata. Author(s): Duplantier N, Finan MA, Barbe T. Source: J Reprod Med. 2003 January; 48(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611090
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Need for biopsy in hepatocellular carcinoma. Author(s): Llatjos M, Muns R, Tallada N. Source: Journal of Hepatology. 2002 December; 37(6): 874; Author Reply 875. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445435
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Needle localization for excisional biopsy of breast lesions: comparison of effect of use of full-field digital versus screen-film mammographic guidance on procedure time. Author(s): Yang WT, Whitman GJ, Johnson MM, Bolanos-Clark M, Kushwaha AC, Hunt KK, Dempsey PJ. Source: Radiology. 2004 April; 231(1): 277-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068954
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Negative 34betaE12 staining in a small focus of atypical glands on prostate needle biopsy: a follow-up study of 332 cases. Author(s): Halushka MK, Kahane H, Epstein JI. Source: Human Pathology. 2004 January; 35(1): 43-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745723
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Neuroendoscopic biopsy for intraventricular tumors. Author(s): Yurtseven T, Ersahin Y, Demirtas E, Mutluer S. Source: Minimally Invasive Neurosurgery : Min. 2003 October; 46(5): 293-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628246
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New fields of application of the sentinel lymph node biopsy in the pathologic staging of solid neoplasms: review of literature and surgical perspectives. Author(s): Gipponi M, Solari N, Di Somma FC, Bertoglio S, Cafiero F. Source: Journal of Surgical Oncology. 2004 March; 85(3): 171-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991890
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Nitrous oxide vs periprostatic nerve block with 1% lidocaine during transrectal ultrasound guided biopsy of the prostate: a prospective, randomized, controlled trial. Author(s): Manikandan R, Srirangam SJ, Brown SC, O'Reilly PH, Collins GN. Source: The Journal of Urology. 2003 November; 170(5): 1881-3; Discussion 1883. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532798
104
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Non-endoscopic gastric mucosal biopsy in dyspepsia. Author(s): Lutfi A, Khan MA, Zuberi SJ. Source: J Pak Med Assoc. 2003 September; 53(9): 432-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620321
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Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. Author(s): Rahman JE, Helou EF, Gelzer-Bell R, Thompson RE, Kuo C, Rodriguez ER, Hare JM, Baughman KL, Kasper EK. Source: Journal of the American College of Cardiology. 2004 February 4; 43(3): 410-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013123
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Nonsentinel lymph node status after positive sentinel lymph node biopsy in early breast cancer. Author(s): Saidi RF, Dudrick PS, Remine SG, Mittal VK. Source: The American Surgeon. 2004 February; 70(2): 101-5; Discussion 105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15011910
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Obesity influences outcome of sentinel lymph node biopsy in early-stage breast cancer. Author(s): Derossis AM, Fey JV, Cody HS 3rd, Borgen PI. Source: Journal of the American College of Surgeons. 2003 December; 197(6): 896-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644276
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Occult "micrometastases" in ductal carcinoma in situ: investigative implications for sentinel lymph node biopsy. Author(s): Weaver DL. Source: Cancer. 2003 November 15; 98(10): 2083-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14601075
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On the need of biopsy confirmation at suspected first recurrence of cancer. Author(s): Cavanna L, Vallisa D, Lazzaro A, Civardi G, Berte R, Moroni CF, Bernuzzi P, Arcari A, Anselmi E. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2004 April; 27(2): 212-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057166
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One 10-core prostate biopsy is superior to two sets of sextant prostate biopsies. Author(s): Fink KG, Hutarew G, Pytel A, Esterbauer B, Jungwirth A, Dietze O, Schmeller NT. Source: Bju International. 2003 September; 92(4): 385-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930426
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Opacified hemithorax with ipsilateral mediastinal shift after transthoracic needle biopsy. Author(s): Barker JM, Sahn SA. Source: Chest. 2003 December; 124(6): 2391-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665527
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Open lung biopsy in neonatal and paediatric patients referred for extracorporeal membrane oxygenation (ECMO). Author(s): Inwald D, Brown K, Gensini F, Malone M, Goldman A. Source: Thorax. 2004 April; 59(4): 328-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15047954
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Open-biopsy-forceps technique for endoscopic removal of distally migrated and impacted biliary metallic stents. Author(s): Matsushita M, Takakuwa H, Nishio A, Kido M, Shimeno N. Source: Gastrointestinal Endoscopy. 2003 December; 58(6): 924-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14652567
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Oral brush biopsy: false positives redux. Author(s): Slater LJ. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2004 April; 97(4): 419. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15134094
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Oral brush biopsy: the problem of false positives. Author(s): Rick GM. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 September; 96(3): 252. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515857
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Oral mucosal dysplastic lesions and early squamous cell carcinomas: underdiagnosis from incisional biopsy. Author(s): Pentenero M, Carrozzo M, Pagano M, Galliano D, Broccoletti R, Scully C, Gandolfo S. Source: Oral Diseases. 2003 March; 9(2): 68-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657031
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Patient perceptions of breast biopsy procedures for screen-detected lesions. Author(s): Geller BM, Oppenheimer RG, Mickey RM, Worden JK. Source: American Journal of Obstetrics and Gynecology. 2004 April; 190(4): 1063-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15118643
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Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma. Author(s): Fincher TR, McCarty TM, Fisher TL, Preskitt JT, Lieberman ZH, Stephens JF, O'Brien JC, Kuhn JA. Source: American Journal of Surgery. 2003 December; 186(6): 675-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672778
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Percutaneous biopsy of periarterial soft tissue cuffs in the diagnosis of pancreatic carcinoma. Author(s): O'Connell MJ, Paulson EK, Jaffe TA, Ho LM. Source: Abdominal Imaging. 2004 January-February; 29(1): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15160764
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Percutaneous musculoskeletal biopsy. Author(s): Choi JJ, Davis KW, Blankenbaker DG. Source: Semin Roentgenol. 2004 January; 39(1): 114-28. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976841
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Polymerase chain reaction of pleural biopsy is a rapid and sensitive method for the diagnosis of tuberculous pleural effusion. Author(s): Hasaneen NA, Zaki ME, Shalaby HM, El-Morsi AS. Source: Chest. 2003 December; 124(6): 2105-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665487
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Predictors of prostate cancer after initial negative systematic 12 core biopsy. Author(s): Singh H, Canto EI, Shariat SF, Kadmon D, Miles BJ, Wheeler TM, Slawin KM. Source: The Journal of Urology. 2004 May; 171(5): 1850-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076292
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Preliminary experience with a new method of endoscopic transbronchial real time ultrasound guided biopsy for diagnosis of mediastinal and hilar lesions. Author(s): Krasnik M, Vilmann P, Larsen SS, Jacobsen GK. Source: Thorax. 2003 December; 58(12): 1083-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645981
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Prion deposition in olfactory biopsy of sporadic Creutzfeldt-Jakob disease. Author(s): Tabaton M, Monaco S, Cordone MP, Colucci M, Giaccone G, Tagliavini F, Zanusso G. Source: Annals of Neurology. 2004 February; 55(2): 294-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755736
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Prognostic value of sentinel lymph node biopsy in the pathologic staging of colorectal cancer patients. Author(s): Bertoglio S, Sandrucci S, Percivale P, Goss M, Gipponi M, Moresco L, Mussa B, Mussa A. Source: Journal of Surgical Oncology. 2004 March; 85(3): 166-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991889
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Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study. Author(s): Ryder SD, Irving WL, Jones DA, Neal KR, Underwood JC; Trent Hepatitis C Study Group. Source: Gut. 2004 March; 53(3): 451-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960533
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Quantitative biopsy pathology for the prediction of pathologically organ-confined prostate carcinoma: a multiinstitutional validation study. Author(s): Haese A, Chaudhari M, Miller MC, Epstein JI, Huland H, Palisaar J, Graefen M, Hammerer P, Poole EC, O'Dowd GJ, Partin AW, Veltri RW. Source: Cancer. 2003 February 15; 97(4): 969-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569595
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Radio-guided occult lesion localization in patients undergoing breast-conserving surgery and sentinel node biopsy. Author(s): Ronka R, Krogerus L, Leppanen E, von Smitten K, Leidenius M. Source: American Journal of Surgery. 2004 April; 187(4): 491-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15041497
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Radioguided sentinel lymph node biopsy in patients with malignant cutaneous melanoma: the nuclear medicine contribution. Author(s): Mariani G, Erba P, Manca G, Villa G, Gipponi M, Boni G, Buffoni F, Suriano S, Castagnola F, Bartolomei M, Strauss HW. Source: Journal of Surgical Oncology. 2004 March; 85(3): 141-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991886
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Radioisotope lymph node mapping in nonsmall cell lung cancer: can it be applicable for sentinel node biopsy? Author(s): Ueda K, Suga K, Kaneda Y, Sakano H, Tanaka T, Hayashi M, Li TS, Hamano K. Source: The Annals of Thoracic Surgery. 2004 February; 77(2): 426-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759410
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Randomized trial of lidocaine vs lidocaine/bupivacaine periprostatic injection on longitudinal pain scores after prostate biopsy. Author(s): Lee-Elliott CE, Dundas D, Patel U. Source: The Journal of Urology. 2004 January; 171(1): 247-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665886
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Re: "Clinicopathologic findings from lacrimal sac biopsy specimens obtained during dacryocystorhinostomy". Author(s): Jordan DR. Source: Ophthalmic Plastic and Reconstructive Surgery. 2004 March; 20(2): 176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15083093
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Re: improved clinical staging system combining biopsy laterality and TNM stage for men with T1c and T2 prostate cancer: results from the search database. Author(s): Buyyounouski MK, Horwitz EM, Hanlon AL, Uzzo RG, Pollack A. Source: The Journal of Urology. 2004 March; 171(3): 1246-7; Author Reply 1247. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767321
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Re-evaluation of non-palpable scalene lymph node biopsy for the staging of nonsmall cell lung cancer. Author(s): Ohno K, Utsumi T, Sasaki Y, Suzuki Y. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2004 April; 25(4): 492-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037260
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Repeating the measurement of prostate-specific antigen in symptomatic men can avoid unnecessary prostatic biopsy. Author(s): Mishra VC, Motiwala HG. Source: Bju International. 2004 May; 93(7): 1116-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15142181
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Right ventricular endomyocardial biopsy findings in 25 patients with sick sinus syndrome. Author(s): Uemura A, Morimoto S, Hiramitsu S, Ohtsuki M, Kato S, Kato Y, Sugiura A, Miyagishima K, Hishida H. Source: Japanese Heart Journal. 2004 January; 45(1): 73-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14973352
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Role of sentinel lymph node biopsy in patients with thick (>4 mm) primary melanoma. Author(s): Jacobs IA, Chang CK, Salti GI. Source: The American Surgeon. 2004 January; 70(1): 59-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964550
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Safety of endobronchial biopsy in 170 children with chronic respiratory symptoms. Author(s): Salva PS, Theroux C, Schwartz D. Source: Thorax. 2003 December; 58(12): 1058-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645975
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Secondary operations are frequently required to complete the surgical phase of therapy in the era of breast conservation and sentinel lymph node biopsy. Author(s): Mullenix PS, Cuadrado DG, Steele SR, Martin MJ, See CS, Beitler AL, Carter PL. Source: American Journal of Surgery. 2004 May; 187(5): 643-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15135683
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Sentinel lymph node biopsy in breast cancer--experience with the combined use of dye and radioactive tracer at Aarhus University Hospital. Author(s): Lauridsen MC, Garne JP, Sorensen FB, Melsen F, Lernevall A, Christiansen P. Source: Acta Oncologica (Stockholm, Sweden). 2004; 43(1): 20-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068316
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Sentinel lymph node biopsy in rectal cancer--not yet ready for routine clinical use. Author(s): Bembenek A, Rau B, Moesta T, Markwardt J, Ulmer C, Gretschel S, Schneider U, Slisow W, Schlag Pm PM. Source: Surgery. 2004 May; 135(5): 498-505; Discussion 506-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15118586
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Sentinel lymph node biopsy is not accurate in predicting lymph node status for patients with cervical carcinoma. Author(s): Marchiole P, Buenerd A, Scoazec JY, Dargent D, Mathevet P. Source: Cancer. 2004 May 15; 100(10): 2154-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15139058
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Sentinel lymph node mapping and biopsy for ductal carcinoma in situ and other controversial indications. Author(s): Fuhrman GM. Source: The American Surgeon. 2004 May; 70(5): 403-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15156947
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Should a biopsy precede liver resection or transplantation for presumed hepatocellular carcinoma when the alfa fetoprotein is normal? Author(s): Shawcross DL, Naoumov N, Pachiadakis I, Mamais C, Williams R, Jalan R, Gillams A, Lees W. Source: Transplantation. 2004 February 27; 77(4): 637-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15084957
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Should tumor mitotic rate and patient age, as well as tumor thickness, be used to select melanoma patients for sentinel node biopsy? Author(s): Thompson JF, Shaw HM. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2004 March; 11(3): 233-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14993013
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Six additional systematic lateral cores enhance sextant biopsy prediction of pathological features at radical prostatectomy. Author(s): Singh H, Canto EI, Shariat SF, Kadmon D, Miles BJ, Wheeler TM, Slawin KM. Source: The Journal of Urology. 2004 January; 171(1): 204-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665877
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Subareolar sentinel node biopsy for multiple breast cancers. Author(s): Layeeque R, Henry-Tillman R, Korourian S, Kass R, Klimberg VS. Source: American Journal of Surgery. 2003 December; 186(6): 730-5; Discussion 735-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672787
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Technical advances in sentinel lymph node biopsy for breast cancer. Author(s): Tuttle TM. Source: The American Surgeon. 2004 May; 70(5): 407-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15156948
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Technical validation of cDNA based microarray as screening technique to identify candidate genes in synovial tissue biopsy specimens from patients with spondyloarthropathy. Author(s): Rihl M, Baeten D, Seta N, Gu J, De Keyser F, Veys EM, Kuipers JG, Zeidler H, Yu DT. Source: Annals of the Rheumatic Diseases. 2004 May; 63(5): 498-507. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15082479
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The biopsy. Author(s): Scarborough MT. Source: Instr Course Lect. 2004; 53: 639-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15116653
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The clinical significance of a small focus of well-differentiated carcinoma at prostate biopsy. Author(s): Hoedemaeker RF, Van der Kwast TH, Schroder FH. Source: Bju International. 2003 December; 92 Suppl 2: 92-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983963
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The effects of irradiation on cell migration from glioblastoma multiforme biopsy spheroids. Author(s): Kleynen CE, Stoter TR, Tadema TM, Stalpers LJ, Dirven CM, Leenstra S, Van Der Valk P, Slotman BJ, Sminia P. Source: Anticancer Res. 2003 November-December; 23(6C): 4907-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981944
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The incidence of prostate cancer in men with prostate specific antigen greater than 4.0 ng/ml: a randomized study of 6 versus 12 core transperineal prostate biopsy. Author(s): Emiliozzi P, Scarpone P, DePaula F, Pizzo M, Federico G, Pansadoro A, Martini M, Pansadoro V. Source: The Journal of Urology. 2004 January; 171(1): 197-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665875
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The safety and quality of endobronchial biopsy in children under five years old. Author(s): Saglani S, Payne DN, Nicholson AG, Scallan M, Haxby E, Bush A. Source: Thorax. 2003 December; 58(12): 1053-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645972
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The use of frozen section and immunohistochemistry for sentinel lymph node biopsy in breast cancer. Author(s): Chao C. Source: The American Surgeon. 2004 May; 70(5): 414-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15156949
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Three-dimensional cytomorphology in fine needle aspiration biopsy of subacute thyroiditis. Author(s): Chang TC, Lai SM, Wen CY, Hsiao YL. Source: Acta Cytol. 2004 March-April; 48(2): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085746
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Transrectal ultrasound-guided biopsy of the prostate gland: value of 12 versus 6 cores. Author(s): O'Connell MJ, Smith CS, Fitzpatrick PE, Keane CO, Fitzpatrick JM, Behan M, Fenlon HF, Murray JG. Source: Abdominal Imaging. 2004 January-February; 29(1): 132-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15160768
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Ubiquinol cytochrome c reductase (UQCRFS1) gene amplification in primary breast cancer core biopsy samples. Author(s): Ohashi Y, Kaneko SJ, Cupples TE, Young SR. Source: Gynecologic Oncology. 2004 April; 93(1): 54-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15047214
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Ultrasound-guided fine-needle aspiration biopsy in nonpalpable thyroid nodules: is it useful in infracentimetric nodules? Author(s): Kim SJ, Kim EK, Park CS, Chung WY, Oh KK, Yoo HS. Source: Yonsei Medical Journal. 2003 August 30; 44(4): 635-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950119
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Ultrasound-guided percutaneous liver biopsy: indications, risks, and technique. Author(s): Copel L, Sosna J, Kruskal JB, Kane RA. Source: Surg Technol Int. 2003; 11: 154-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12931297
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Understanding the role of sentinel lymph node biopsy in breast cancer and melanoma. Author(s): Blanchard E, Herman L, Larson L, Leger MM, McNellis R, Quigley T, Toth S, Van Dyke E. Source: Jaapa. 2003 December; 16(12): 49-50, 54. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14758688
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Upregulation of redox-regulating protein, thioredoxin, in endomyocardial biopsy samples of patients with myocarditis and cardiomyopathies. Author(s): Nimata M, Kishimoto C, Shioji K, Ishizaki K, Kitaguchi S, Hashimoto T, Nagata N, Kawai C. Source: Molecular and Cellular Biochemistry. 2003 June; 248(1-2): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12870673
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Upstaging of atypical ductal hyperplasia after vacuum-assisted 11-gauge stereotactic core needle biopsy. Author(s): Winchester DJ, Bernstein JR, Jeske JM, Nicholson MH, Hahn EA, Goldschmidt RA, Watkin WG, Sener SF, Bilimoria MB, Barrera E Jr, Winchester DP. Source: Archives of Surgery (Chicago, Ill. : 1960). 2003 June; 138(6): 619-22; Discussion 622-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799332
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Use of 18F-choline and 11C-choline as contrast agents in positron emission tomography imaging-guided stereotactic biopsy sampling of gliomas. Author(s): Hara T, Kondo T, Hara T, Kosaka N. Source: Journal of Neurosurgery. 2003 September; 99(3): 474-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959432
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Use of interphase fluorescence in situ hybridization in prostate needle biopsy specimens with isolated high-grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on follow-up biopsy. Author(s): Bastacky S, Cieply K, Sherer C, Dhir R, Epstein JI. Source: Human Pathology. 2004 March; 35(3): 281-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017583
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Use of myocardial biopsy catheter in retrieving "lost" intracardiac device. Author(s): Cheng TO. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2003; 30(2): 165. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809266
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Usefulness of endoscopic biopsy using immunostaining of p53 and Ki-67 in tumors of the ampulla of Vater. Author(s): Kubota K, Kakuta Y, Kawamura S, Saito S, Seki H, Kuniyoshi T. Source: Pathology International. 2003 June; 53(6): 361-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12787310
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Vacuum-assisted breast biopsy: a critical review. Author(s): Hoorntje LE, Peeters PH, Mali WP, Borel Rinkes IH. Source: European Journal of Cancer (Oxford, England : 1990). 2003 August; 39(12): 167683. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888361
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Validity of simple mucosal biopsy criteria combined with endoscopy predicting patients with ulcerative colitis ultimately requiring surgery: a multicenter study. Author(s): Tanaka M, Kusumi T, Oshitani N, Nishigami T, Iwao Y, Hatada Y, Sugita A, Yao T, Takano M, Iizuka B, Mukai M, Maeda K, Fukuda S, Morita T, Hara M, Saito H, Kudo H. Source: Scandinavian Journal of Gastroenterology. 2003 June; 38(6): 594-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825866
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Value of core needle biopsy in the diagnosis of soft tissue tumours. Author(s): Madhavan VP, Smile SR, Chandra SS, Ratnakar C. Source: Indian J Pathol Microbiol. 2002 April; 45(2): 165-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12696732
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Value of three-dimensional sonography in biopsy of focal liver lesions. Author(s): Polakow J, Janica J, Serwatka W, Ladny JR, Zukowska-Serwatka K. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2003; 10(1): 87-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827478
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Vascular parkinsonism in moyamoya: microvascular biopsy and imaging correlates. Author(s): Tan EK, Chan LL, Yu GX, Rumpel H, Wilder-Smith E, Wong MC. Source: Annals of Neurology. 2003 December; 54(6): 836-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681896
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Ventricular natriuretic peptide (BNP) in heart transplantation: BNP correlation with endomyocardial biopsy, laboratory and hemodynamic measures. Author(s): Hervas I, Arnau MA, Almenar L, Perez-Pastor JL, Chirivella M, Osca J, Bello P, Osa A, Marti JF, Vera F, Mateo A. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2004 January; 84(1): 138-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631384
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Verification bias and the prostate-specific antigen test--is there a case for a lower threshold for biopsy? Author(s): Schroder FH, Kranse R. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 393-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878747
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VIP and PACAP receptors coupled to adenylyl cyclase in human lung cancer: a study in biopsy specimens. Author(s): Busto R, Prieto JC, Bodega G, Zapatero J, Fogue L, Carrero I. Source: Peptides. 2003 March; 24(3): 429-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732341
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Visceral leshmaniasis diagnosed on duodenal biopsy in a child. Author(s): Boukthir S, Mejri A, M'rad S, Barsaoui S. Source: Acta Gastroenterol Belg. 2003 July-September; 66(3): 258-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618961
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Voiding impairment after prostate biopsy: does tamsulosin treatment before biopsy decrease this morbidity? Author(s): Bozlu M, Ulusoy E, Doruk E, Cayan S, Canpolat B, Schellhammer PF, Akbay E. Source: Urology. 2003 December; 62(6): 1050-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665353
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Wegener's granulomatosis diagnosed by testicular biopsy. Author(s): Agraharkar M, Gokhale S, Gupta R. Source: International Urology and Nephrology. 2002-2003; 34(4): 559-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14577505
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When is a diagnosis of sclerosing adenosis acceptable at core biopsy? Author(s): Gill HK, Ioffe OB, Berg WA. Source: Radiology. 2003 July; 228(1): 50-7. Epub 2003 May 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738875
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When is liver biopsy needed in the diagnosis of primary biliary cirrhosis? Author(s): Zein CO, Angulo P, Lindor KD. Source: Clin Gastroenterol Hepatol. 2003 March; 1(2): 89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017500
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When is sentinel node biopsy for breast cancer contraindicated? Author(s): Krontiras H, Bland KI. Source: Surgical Oncology. 2003 November; 12(3): 207-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957625
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When to biopsy and when to stop biopsying. Author(s): Djavan B, Remzi M, Marberger M. Source: The Urologic Clinics of North America. 2003 May; 30(2): 253-62, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12735502
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Whipple's disease: immunospecific and quantitative immunohistochemical study of intestinal biopsy specimens. Author(s): Lepidi H, Fenollar F, Gerolami R, Mege JL, Bonzi MF, Chappuis M, Sahel J, Raoult D. Source: Human Pathology. 2003 June; 34(6): 589-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827613
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Will subareolar injection be a standard technique for sentinel lymph node biopsy? Author(s): Yoshida K, Yamamoto N, Imanaka N, Togawa T, Miyauchi M, Miyazaki M. Source: Breast Cancer. 2002; 9(4): 319-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459713
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Will the spectrum of lesions prompting a "B3" breast core biopsy increase the benign biopsy rate? Author(s): Carder PJ, Liston JC. Source: Journal of Clinical Pathology. 2003 February; 56(2): 133-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560393
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Windows on renal biopsy interpretation: does mRNA analysis represent a new gold standard? Author(s): Striker LJ, Striker GE. Source: Journal of the American Society of Nephrology : Jasn. 2003 April; 14(4): 1096-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660345
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Women's choice between sentinel lymph node biopsy and axillary clearance. Author(s): Gan S, Magarey C, Schwartz P, Papadatos G, Graham P, Vallentine J. Source: Anz Journal of Surgery. 2002 February; 72(2): 110-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074061
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CHAPTER 2. NUTRITION AND BIOPSY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and biopsy.
Finding Nutrition Studies on Biopsy 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 “biopsy” (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 information is typical of that found when using the “Full IBIDS Database” to search for “biopsy” (or a synonym): •
Same-day lymphoscintigraphy and sentinel node biopsy for early breast cancer. Author(s): Breast Unit and Women's Health Centre, Royal Adelaide Hospital Cancer Centre, Adelaide University Department of Surgery, South Australia, Australia. Source: Sutton, R Kollias, J Prasad, V Chatterton, B Grantley Gill, P ANZ-J-Surg. 2002 August; 72(8): 542-6 1445-1433
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Transrectal core biopsy trauma may increase cell proliferation in prostate tumors. Author(s): Department of Pathology, Umea University, Umea, Sweden.
[email protected] Source: Bergh, A Bylund, A Lundin, E Hallmans, G Stattin, P Scand-J-Urol-Nephrol. 2002; 36(4): 311-3 0036-5599
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
Nutrition
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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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND BIOPSY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to biopsy. 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 biopsy 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 “biopsy” (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 biopsy: •
Hyperbaric oxygen therapy for air embolism complicating CT-guided needle biopsy of the lung. Author(s): Ashizawa K, Watanabe H, Morooka H, Hayashi K. Source: Ajr. American Journal of Roentgenology. 2004 June; 182(6): 1606-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15150026
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Is massage following dye injection necessary in sentinel node biopsy in breast cancer? Author(s): Shenoy V, Ravichandran D, Ralphs DN. Source: Breast (Edinburgh, Scotland). 2002 June; 11(3): 273-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14965682
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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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WebMDHealth: 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 biopsy; 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 Abnormal Pap Smear Source: Healthnotes, Inc.; www.healthnotes.com Alopecia Source: Integrative Medicine Communications; www.drkoop.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Ascariasis Source: Integrative Medicine Communications; www.drkoop.com Bone Cancer Source: Integrative Medicine Communications; www.drkoop.com Bone Marrow Disorders Source: Integrative Medicine Communications; www.drkoop.com
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Brain Cancer Source: Integrative Medicine Communications; www.drkoop.com Burns Source: Integrative Medicine Communications; www.drkoop.com Cervical Dysplasia Source: Integrative Medicine Communications; www.drkoop.com Chronic Myelogenous Leukemia Source: Integrative Medicine Communications; www.drkoop.com Cirrhosis Source: Integrative Medicine Communications; www.drkoop.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Fever of Unknown Origin Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Integrative Medicine Communications; www.drkoop.com Guinea Worm Disease Source: Integrative Medicine Communications; www.drkoop.com Hair Loss Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Hookworm Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Leukemia Source: Integrative Medicine Communications; www.drkoop.com Liver Disease Source: Integrative Medicine Communications; www.drkoop.com Loiasis Source: Integrative Medicine Communications; www.drkoop.com
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Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Lymphatic Filariasis Source: Integrative Medicine Communications; www.drkoop.com Lymphoma Source: Integrative Medicine Communications; www.drkoop.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Myelofibrosis Source: Integrative Medicine Communications; www.drkoop.com Myeloproliferative Disorders Source: Integrative Medicine Communications; www.drkoop.com Pinworm Source: Integrative Medicine Communications; www.drkoop.com Polycythemia Vera Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com River Blindness Source: Integrative Medicine Communications; www.drkoop.com Roundworms Source: Integrative Medicine Communications; www.drkoop.com Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Stomach Inflammation Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com
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Threadworm Source: Integrative Medicine Communications; www.drkoop.com Thrombocytosis Source: Integrative Medicine Communications; www.drkoop.com Trichinosis Source: Integrative Medicine Communications; www.drkoop.com Tuberculosis Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Visceral Larva Migrans Source: Integrative Medicine Communications; www.drkoop.com Whipworm Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Bioelectronic Diagnosis Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/b.html Chelation Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,679,00.html De La Warr System Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/d.html Radionics Alternative names: psionics Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/r.html Spirituality Source: Integrative Medicine Communications; www.drkoop.com
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Herbs and Supplements Aristolochia Alternative names: Snakeroot, Guaco; Aristolochia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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 BIOPSY Overview In this chapter, we will give you a bibliography on recent dissertations relating to biopsy. 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 “biopsy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on biopsy, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Biopsy 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 biopsy. 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: •
Prognosis in systemic lupus erythematosus the contribution of renal biopsy and variables that change through time by McLaughlin, John Ross; PhD from University of Toronto (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54638
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The relationship of endometrial biopsy and rectal palpation findings to reproductive performance in postpartum cows by Bonnett, Brenda Nora; PhD from University of Guelph (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL44904
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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. PATENTS ON BIOPSY 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.8 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 “biopsy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on biopsy, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Biopsy By performing a patent search focusing on biopsy, 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
8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on biopsy: •
Apoptotic bodies, monocyte derived cells containing the same, a process for their preparation and their uses as vaccines Inventor(s): Bartholeyns; Jacques (Bures-sur-Yvette, FR), Gregoire; Marc (Nantes, FR) Assignee(s): IDM Immuno -Design Molecules (Paris, FR), INSERM Institut National de la Sante et de la Recherche Medicale (Paris Cedex, FR) Patent Number: 6,703,016 Date filed: December 28, 2000 Abstract: The present invention relates to apoptotic bodies derived from human tumor cells or cell lines recovered from patient's tumor biopsy and induced to apoptotis, said apoptotic bodies having the following characteristics: they maintain plasma membrane integrity, they are vesicles above about 0,1.mu.m, they contain intact mitochondria and cleaved nuclear DNA originating from the tumor cells, they present unmasked tumor antigens on their membranes, they present specific tumor and MHC antigens from the patient. The invention also provides new monocytes derived cells, which can be used as anti-tumor vaccines after integration of apoptotic bodies. Apoptotic bodies are phagocytosed and processed by monocyte derived antigen presenting cells and potentiate the effective tumor antigenic presentation to the immune system. Excerpt(s): The present invention relates to new apoptotic bodies, monocyte derived cells containing the same, a process for their preparation and their uses as vaccines. In advanced cancer, tumor cells are notoriously poor immunogens in vivo. In vitro, the immune system can recognize and kill tumor cells. Tumor cells have antigens for T cells, as reported for melanoma.sup.1, but lack immunogenicity in vivo. Probably, tumor antigens are either masked, not presented by specialized cells or suppressed by the tumor milieu. The use of vaccines consisting of peptides.sup.2 or single transfected.sup.3, antigen presented by professional antigen presenting cells (APC).sup.4, caused limited benefits in antitumoral therapies.sup.5,6 because of the narrowness of specificity and immune escape. An alternative strategy is to use unfractionated or fractionated tumor cells.sup.7,8,9 limited to immunogenic tumors. Programmed Cell Death (PCD) is the most common form of eukaryotic cell death. The term of apoptosis, which is often equated with PCD, refers to morphological alterations exhibited by dying cells. In contrast to necrosis, apoptosis is an active process. Apoptosis occurs under normal and pathological physiological conditions, the cell being an active participant of its own "cellular suicide", and cells undergoing apoptosis show characteristic morphological and biochemical features. Web site: http://www.delphion.com/details?pn=US06703016__
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Arrangement for the examination of an object Inventor(s): Joensuu; Raimo (Oksasenkatu 7 A 53, FIN-00100, Helsinki, FI) Assignee(s): none reported Patent Number: 6,682,492 Date filed: April 26, 2001
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Abstract: An operation instrument for the examination of an object, for example a biopsy needle, a catheter, or a radioactive capsule intended for radiotherapy. The instrument comprises an active component which is adapted to be detected with a nuclear magnetic resonance method, such as magnetic imaging, in such a way that the active component contains a marker which carries NMR-active nuclei and, in interaction with the marker, an enhancer which causes the enhancement of an NMR signal by means of dynamic nuclear polarization as a result of saturating the electron spin system of the enhancer which causes the enhancement of an NMR signal by means of dynamic nuclear polarization as a result of saturating the electron spin system of the enhancer with an external energy, so-called saturation energy. The operation instrument comprises a marker container and a transfer linen for transferring the saturation energy into the enhancer. The marker is housed in a metal foil, and a boundary surface between the transfer line and the marker container is tapered. The transfer line is provided with an inner conductor extending into the marker container over a substantial distance into the interior of the container. Excerpt(s): The present invention relates to the examination of an object, such as a human body, for example, and possibly to the simultaneous guidance of a treatment procedure. The nuclear magnetic resonance phenomenon (NMR) has already been applied in medicine to magnetic resonance imaging (MRI) for more than ten years. The design of various pieces of magnetic imaging equipment and the use of various techniques have been dealt with in a number of books and the latest research results are currently published in several scientific journals focusing exclusively on that particular field. A common feature for all magnetic imaging devices is the positioning of an object to be imaged, often a patient, in a stationary magnetic field B.sub.0.uparw. which is produced by a magnet. In addition to this, the magnetic field is subjected to a linear magnetic-field change, a gradient, which is effected by means of a special gradient coil. The magnetic imaging devices are provided with three gradients G.sub.x, G.sub.y, and G.sub.z, which represent the change of a magnetic field in the direction of an x, y, and z axis, respectively. The gradients are used for encoding positional information from the magnetically resonating material, most commonly protons, of an object to be imaged, by frequency-modulating the resonance. The signal for magnetic imaging is produced by means of radio-frequency (RF) coils, which excite the resonance and function as a signal receiver. The signal is analyzed (Fourier-transformed) for its frequency content, thereby determining a signal distribution in the direction to be examined. The literature discloses a variety of methods for applying this basic technique for producing 2- or 3dimensional images by using special imaging sequences, which are all based on the encoding of an NMR signal effected by means of gradients in x, y, and z directions. Web site: http://www.delphion.com/details?pn=US06682492__ •
Automated biopsy instruments Inventor(s): Chau; Sonny (Gurnee, IL), Como-Rodriguez; Jan (Libertyville, IL), Kupec; Thomas (Gurnee, IL) Assignee(s): Allegiance Corporation (McGaw Park, IL) Patent Number: 6,626,850 Date filed: March 30, 1998 Abstract: The present invention provides automated biopsy instruments especially useful for improving minimally invasive medical procedures to obtain soft tissue biopsy samples. The biopsy instruments provide side-by-side actuators which retract a stylet
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and a cannula in specific sequences. The biopsy instruments may include a single spring or two springs to sequentially fire the stylet and the cannula. Excerpt(s): This invention generally relates to biopsy instruments. More specifically, this invention relates to automated biopsy instruments especially useful for improving minimally invasive medical procedures to obtain soft tissue biopsy samples. A soft tissue biopsy procedure is a medical procedure for removing a soft tissue sample from a human or animal. The tissue sample can be analyzed to assist a medical professional in formulating a diagnosis. The biopsy procedure is a minimally invasive procedure for obtaining the tissue sample. The biopsy procedure can be performed utilizing various techniques and devices. Typically, a biopsy device includes an inner stylet slidably positioned inside an outer cannula. The stylet is a solid, pointed needle having a tissue sampling recess, and the cannula is a hollow, open ended needle having a sharp tip. The stylet and the cannula are manipulated to capture a tissue sample in the sample recess. Existing biopsy devices include manual, semi-automated, and automated devices. Web site: http://www.delphion.com/details?pn=US06626850__ •
Biological filtration station Inventor(s): Critz; Carl H. (24 Tea Tree Ct., Danville, CA 94526), Hale; Joseph H. (14 Mayo Dr., Warren, RI 02885) Assignee(s): none reported Patent Number: 6,629,612 Date filed: March 30, 2001 Abstract: A filtration station for capturing small to medium sized tissue fragments in fluid for histological processing. The filtration station allows tissue to be filtered onto foam in a cassette or into a biopsy bag with speed, excellent tissue recovery and convenient fixative collection for recycling or disposal. The present invention combines two normally separate filtration stations into one station for more convenient filtration of tissue into two widely used filter media while also reducing exposure to harmful vapors. Excerpt(s): This invention relates to the general art of analysis of tissue samples, and in particular to obtaining, handling and processing small to medium sized tissue samples in fluid for histological processing. Various disease processes, particularly tumors, require a histologic diagnosis. Cell types of a tumor are generally determined by a pathologist's examination of a histologic sample of the tumor. There are a number of devices that have been fashioned to actually perform the act of taking tissue samples. In many cases, these samples are very small and difficult to retrieve and process. The small tissue fragments originating from various biopsy procedures are generally rinsed into a specimen container with a preservative effluent, such as 10% formalin, to prevent loss of the sample, dehydration of the sample, and contamination of the sample during harvesting, storage and transport. For actual histological diagnosis, the tissue specimen must be separated from the effluent. The smallness of the samples make it very difficult and time consuming to separate and process the samples in the laboratory. Upon separation, it is desirable to immobilize the pieces of tissue within some device such as sponge or in filter paper biopsy bag which resembles tea bag to prevent them from becoming lost during processing. Web site: http://www.delphion.com/details?pn=US06629612__
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Biopsy and coagulant device Inventor(s): Krause; William R. (Charlottesville, VA), Classe; Francis C. (New York, NY) Assignee(s): Bioengineering Consultants (Charlottesville, VA) Patent Number: 6,702,760 Date filed: November 6, 2001 Abstract: The biopsy device has a biopsy channel connected to an aspiration and collecting chamber and at least one application channel connected to a dispensing chamber integrally connected with the aspiration chamber. The application channel is formed by a tube centrically slipped over the biopsy channel wall. To enable the collection of tissue specimens without tissue specimens entering and obstructing the application cannula, the distal segment of the application channel forms a close fitting and concentric sheath around the biopsy channel. The proximal end of the application channel has a larger diameter than the distal end allowing for unobstructed flow of the application material past the biopsy channel wall upon retraction of the biopsy channel from the distal segment of the application channel. Excerpt(s): The present invention relates to a biopsy device that takes a biopsy sample of human or animal tissue and delivers a coagulant or other material to the biopsy incision track in order to plug the track and prevent bleeding. Excision biopsy of the liver has traditionally been the gold standard for assessing the extent of injury and determining prognosis in chronic viral hepatitis and liver cancer. A significant complication that frequently occurs is bleeding from the biopsy site. Significant hemorrhage occurs in 0.35 to 0.5% of all procedures while evidence of sub-clinical bleeding, as detectable by ultrasound 24 hours post biopsy, has been reported in up to 23% of patients. Smaller amounts of surface bleeding is almost universal and is frequently associated with mild to moderate pain. Excision biopsies from other organs, such as the lungs, also exhibit a relatively high complication rate due to hemorrhagic incidents and pneumothorax. Also with kidney biopsies and biopsies of other organs, perfuse bleeding is considered the most important complication. Web site: http://www.delphion.com/details?pn=US06702760__
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Biopsy device with adjustable sampling Inventor(s): Bauer; Alberto (Pieve di Cento, IT) Assignee(s): Allegiance Corporation (Mcgaw Park, IL) Patent Number: 6,749,576 Date filed: February 3, 2003 Abstract: The invention relates to a biopsy device having the ability to adjust the size of the sample to be removed. The biopsy device includes biopsy needle assembly and cannula insertion guide co-axially aligned therewith such that longitudinal adjustment of the cannula insertion guide likewise adjusts the exposure of the stylet and cutting edge of the biopsy needle assembly thereby changing the size of the resulting sample. A longitudinal adjusting element is positioned between and connects the cannula insertion guide and housing of the device. The invention is particularly useful in biopsy procedures where improved control over sample size and cutting stroke are desirable. Excerpt(s): The invention relates to a device for tissue removal in biopsy procedures. In particular, the invention relates to a manually operated biopsy device containing an
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adjustable biopsy needle. Biopsy needle devices with handpieces containing an actuating apparatus which activates the motion of a biopsy needle are known. For example, U.S. Pat. No. 4,958,625 to Bates et al. discloses a biopsy device containing a handpiece and stylet which projects independently of a cannula and wherein the handpiece contains an attachment means for the cannula. The insertion guide used in such systems includes a cannula guide made up of a hollow small tube in which the proximal end bears a trigger, and is equipped with an attachment means, as well as a luer lock for a syringe to introduce a medicament to the site after tissue removal. Procedures using actuated biopsy needles typically involve first inserting the biopsy needle and cannula insertion guide into the patient's body by positioning the distal end of the needle in proximity to the object to be sampled. Upon determining the desired position by magnetic resonance (CAT scan) or other technique, the stylet and cannula cutting edge are sequentially activated to obtain the sample. Once the sampling step has been performed, the attachment means are released and the biopsy needle withdrawn from the cannula insertion guide to check the sample. If the sample is incorrect or otherwise insufficient, a new biopsy needle is inserted into the cannula insertion guide and the sampling sequence is repeated. After obtaining the desired sample, a medicament can be administered to the site by applying a syringe to the insertion guide. Web site: http://www.delphion.com/details?pn=US06749576__ •
Biopsy localization method and device Inventor(s): Dubrul; William Richard (Redwood CIty, CA), Fulton, III; Richard Eustis (Grand Junction, CO) Assignee(s): Artemis Medical, Inc. (Hayward, CA) Patent Number: 6,699,205 Date filed: July 6, 2001 Abstract: A biopsy localization device made according to the invention includes a bioabsorbable element (34), such as a dehydrated collagen plug, delivered in a predelivery state to a soft tissue biopsy site (18) of a patient by an element delivery device (32). The bioabsorbable element preferably swells to fill the biopsied open region (26) and preferably is palpably harder than the surrounding soft tissue at the biopsy site. The bioabsorbable element permits the biopsy site to be relocated by palpation to eliminate the need to use metallic clips during biopsies and often eliminates the need for a return to the radiologist for pre-operative localization. In addition, the bioabsorbable element can be used as a therapeutic tool for treatment of the diseased lesion and for hemostasis. Excerpt(s): Locating the previously biopsied area after surgical excision type of biopsy is usually not a problem because of the deformity caused by the surgery. However, if the biopsy had been done with an image directed needle technique, as is common, help in relocating the biopsy site is usually needed. One procedure to permit the biopsy site to be relocated by the radiologist during preoperative localization is to leave some of the suspicious calcifications; this has its drawbacks. Another way to help the radiologist relocate the biopsy site involves the use of a small metallic surgical clip, such as those made by Biopsys. The metallic clip can be deployed through the biopsy needle, and is left at the biopsy site at the time of the original biopsy. With the metallic clip as a guide, the radiologist typically inserts a barbed or hooked wire, such as the Hawkins, Kopans, Homer, Sadowski, and other needles, back into the patient's breast and positions the tip of the wire at the biopsy site using mammography to document the placement. The
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patient is then taken to the operating room with the needle apparatus sticking out of the patient's breast. While the clip provides a good indication of the biopsy site to the radiologist during preoperative localization, the clip remains permanently within the 80% of patients with benign diagnoses. Also, because the clip is necessarily attached to a single position at the periphery of the biopsy site, rather than the center of the biopsy site, its location may provide a misleading indication of the location of diseased tissue during any subsequent medical intervention. In addition, the soft nature of breast tissue permits the tip of the barbed or hooked needle to be relatively easily dislodged from the biopsy site. The clip is also relatively expensive. Another localization method involves the use of laser light from the tip of a optical fiber connected to a laser. A pair of hooks at the tip of the optical fiber secures the tip at the biopsy site; the glow indicates the position of the tip through several centimeters of breast tissue. This procedure suffers from some of the same problems associated with the use of barbed or hooked wires. Another preoperative localization procedure injects medical-grade powdered carbon suspension from the lesion to the skin surface. This procedure also has certain problems, including the creation of discontinuities along the carbon trail. Web site: http://www.delphion.com/details?pn=US06699205__ •
Biopsy needle for continuous sample removal Inventor(s): Finer; Richard (551 Alta Vista Dr., Sierra Madre, CA 91024-1412) Assignee(s): none reported Patent Number: 6,730,045 Date filed: June 22, 2001 Abstract: Described herein is a biopsy needle comprising a hollow outer tube at the end of which is a rectangular opening having sharpened edges. In preferred embodiments, the needle has one lumen formed by the needle or two lumens, formed either by a second hollow member positioned within the needle, or a ------- semi-circular tube inserted within the needle. To remove tissue using the needle, one inserts it into a patient's body, applies suction to the single or double lumens and then rotates the needle. Tissue is drawn into the needle lumen for subsequent evaluation by a Pathologist. Excerpt(s): Embodiments of the present invention are directed to a biopsy needle for removal of tissue from a body for examination outside of the body. A biopsy needle is used to obtain a sample of tissue from the body (usually from the human body, but often from the body of a non-human animal, as well) for diagnosis of disease or other examination. The sample obtained should be uniform and substantial enough to permit one to examine its structure and composition. When the sample is used for diagnosing disease, the sample should be representative of the tissue from which the sample is removed. If the sample is obtained with the proper technique and a correct instrument, it will be large and uniform enough to make diagnostically relevant findings from it. The challenge in biopsy needle design is principally to meet two conflicting goals: 1) provide a needle that is large enough to obtain a sample of sufficient size; and 2) provide a needle that is small enough to minimize trauma to the patient. Minimizing trauma means more than minimizing pain (about which the patient cares a great deal, of course): a smaller incision in the body heals more quickly, bleeds less, minimizes infection, and reduces scarring. Current biopsy design meets these goals with varying degrees of success; many designs meet one goal but at significant expense to the other.
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Web site: http://www.delphion.com/details?pn=US06730045__ •
Biopsy needle instrument Inventor(s): Hamann; David L. (4248 Kirby Ave., Cincinnati, OH 45223), Kaplan; Leopold S. (172 Linda La., Edison, NJ 08820), Kelly; Lawrence J. (1934 Resor Rd., Fairfield, OH 45014) Assignee(s): none reported Patent Number: 6,689,072 Date filed: November 13, 2001 Abstract: An automated fine needle biopsy device is described for extracting tissue from the body predominantly in suspected cases of breast cancer. However, it can be used in other parts of the body accessible to needle biopsy. The device causes a fine needle, which is attached to the device, to reciprocate and/or rotate at the same time causing tissue to enter the needle. The depth and number of the thrusts can be pre-programmed, and the force behind each thrust is constant. Suction may or may not be used. The tissue extracted is subsequently expelled onto glass slides for microscopic interpretation. This device and method offer a vast improvement over the present method for fine needle biopsy wherein it is performed manually and in a very haphazard way. Excerpt(s): The present invention relates in general to the field of medical biopsy instruments, and more particularly, to such instruments for use in fine needle biopsy of human or animal tissue for medical diagnostics and the like. Biopsy instruments are often used to obtain tissue samples for microscopic examination to test for malignancy or other diseases and abnormalities. Generally, biopsies may be guided by either stereotactic means, CAT scan or ultrasound means. Image-guided biopsy procedures are particularly useful for non-surgical diagnosis of benign and malignant masses. The biopsy itself may be either a core biopsy or a fine needle aspiration biopsy. For example, an instrument for performing percutaneous biopsy procedures and collection of soft tissue is disclosed in Ritchant, et al., U.S. Pat. No. 5,649,547. Other currently used biopsy instruments and methods include those disclosed in Siczek, et al., U.S. Pat. No. 5,415,169 and Assa, U.S. Pat. No. 5,240,011, Siczek, et al. and Assa each disclose a motorized biopsy needle positioner employed in a mammographic needle biopsy system for receiving coordinate information representative of an identified point of interest within the patient's captive breast under examination and automatically positioning a biopsy needle in accordance with the coordinate information to permit insertion of the biopsy needle to the identified point of interest. Web site: http://www.delphion.com/details?pn=US06689072__
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Biopsy sampler Inventor(s): Diamond; Bruce H. (Wellesley, MA), Roberts; Troy W. (Pepperell, MA), Shaw; William J. (Cambridge, MA) Assignee(s): SciMed Life Systems, Inc. (Maple Grove, MN) Patent Number: 6,692,445 Date filed: July 16, 2001
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Abstract: The invention features an assembly for taking a biopsy sample from a site within the body of a patient. The assembly includes a resecting device having a cutter near its distal end for resecting and containing a tissue sample and a sheath exterior to the resecting device and sized to be present within the body with the resecting device. The sheath includes an electrode element electrically isolated from the resecting device and disposed on the sheath's outer surface for cauterizing tissue. The electrode element may reside on the outer sheath, the distal end or both the outer sheath and the distal end of the assembly. The resecting device and the sheath cooperate to permit sequential resecting of a tissue sample from a resecting site and cauterizing of the site with the cutter sufficiently spaced from the electrode element to avoid heat damage to the tissue sample. Excerpt(s): This invention relates to biopsy sampling. There are many biopsy procedures in which tissue samples are taken for later histology. In "cold" biopsy procedures, surgical forceps are inserted within, for example, an endoscope, and are used to resect (i.e., cut) a tissue sample from, for instance, the biliary tree or colon. The forceps, and, hence, the tissue sample, are then removed from the patient through the endoscope. Extensive bleeding can occur as a result of cold resecting, which can lead to dangerous blood loss levels. Hence, after the tissue sample is removed, another device can be inserted into the patient through the endoscope to stop the bleeding. These devices include tamponade devices which apply pressure to the bleeding site to stop the bleeding, devices which apply alcohol to the bleeding site to stop the bleeding, and electro-cautery devices which apply radio frequency (RF) energy to one or more electrodes (monopolar or bipolar) in contact with the bleeding site to cauterize the tissue and stop the bleeding. Following resecting, time is required to remove the forceps and tissue sample and insert a device to stop the bleeding. During this time, the resecting site continues to bleed. Web site: http://www.delphion.com/details?pn=US06692445__ •
Biopsy system Inventor(s): Viola; Frank (Sandy Hook, CT) Assignee(s): Tyco Healthcare Group LP (Norwalk, CT) Patent Number: 6,712,773 Date filed: September 11, 2000 Abstract: A biopsy system for retrieving biopsy tissue samples from different regions of the body is disclosed. The biopsy system includes a single use loading unit having a trocar assembly and a knife assembly. A trocar driver is operably connected to the trocar assembly and is actuable to move a trocar between retracted and advanced positions. The trocar driver is disengaged from the trocar assembly prior to firing the trocar into a target tissue mass to reduce drag on the trocar during firing. A knife driver is operably connected to the knife assembly such that when actuated, a knife is both rotatably and axially advanced about the trocar. Excerpt(s): This disclosure relates to an apparatus and method for the biopsy of tissue specimens and, more particularly, to a single insertion, multiple sample percutaneous biopsy system and method of use. It is often necessary to sample tissue in order to diagnose and treat patients suspected of having cancerous tumors, pre-malignant conditions and other diseases or disorders. Typically, in the case of suspected cancerous tissue, when the physician establishes by means of procedures such as palpation, x-ray
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or ultrasound imaging that suspicious conditions exist, a biopsy is performed to determine whether the cells are cancerous. Biopsy may be done by an open or percutaneous technique. Open biopsy removes the entire mass (excisional biopsy) or a part of the mass (incisional biopsy). Percutaneous biopsy on the other hand is usually done with a trocar-like instrument and may be either a fine trocar aspiration (FNA) or a core biopsy. In FNA biopsy, individual cells or clusters of cells are obtained for cytologic examination and may be prepared such as in a Papanicolaou smear. In core biopsy, as the term suggests, a core or fragment tissue is obtained for histologic examination which may be done via frozen section or paraffin section. In more recent developments percutaneous techniques have been used to remove the entire mass during the initial procedure. The type of biopsy utilized depends in large part on the circumstances present with respect to the patient and no single procedure is ideal for all cases. Core biopsy, however, is extremely useful in a number of conditions and is being used more frequently. Web site: http://www.delphion.com/details?pn=US06712773__ •
Bone marrow biopsy needle Inventor(s): Clark; Grant A. (Bristol, WI), Krueger; John (Milwaukee, WI) Assignee(s): Allegiance Corporation (McGaw Park, IL) Patent Number: 6,730,043 Date filed: March 5, 2001 Abstract: The present invention provides a bone marrow biopsy device 10 that includes a handle, an outer cannula, a stylet, and an inner member. The outer cannula is secured in the handle. The outer cannula defines a distal tip that is tapered to provide a distal cutting edge. The stylet is designed to be inserted in the outer cannula. The stylet defines a sharp distal tip. The inner member is designed to be inserted in the outer cannula. The inner member defines a cutting finger. Excerpt(s): The present invention relates to medical instruments utilized in securing marrow tissue samples from bone structures. A biopsy medical instrument is an instrument which is designed to take samples of tissue. Typically, a biopsy device that is utilized to obtain samples from bone consists of a hollow cannula that is surrounding a stylet. The stylet includes a sharp distal tip which extends outwardly from the cannula when the stylet is secured inside the cannula. The combined cannula and stylet is used to penetrate through the outer layer of the bone, called the cortex, which is considerably harder than the trabecular bone layer and the tissue within the bone that is sampled, referred to as the marrow. Once the stylet is removed and the cannula is extended further into the medular cavity, thereby capturing marrow tissue for a sample. The architecture of the tissue sample that is removed by the biopsy device is critical in several respects. Initially, the size of the sample is important, with larger tissue sample sizes representing better samples for subsequent testing to be performed on the tissue. However, the larger the cannula and stylet that are inserted into the bone, the more pain is generated at the site of the penetration for the patient. In addition, it is important that the sample be taken without damaging the marrow tissue. However, in removing the tissue sample the tissue must be excised from the remaining tissue. This removal can result in compromising the tissue sample by damaging the tissue sample. Web site: http://www.delphion.com/details?pn=US06730043__
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Breast biopsy system and methods Inventor(s): Burbank; Fred H. (San Juan Capistrano, CA), Jones; Michael L. (Capistrano Beach, CA), Lubock; Paul (Laguna Niguel, CA) Assignee(s): SenoRx, Inc. (Aliso Viejo, CA) Patent Number: 6,699,206 Date filed: October 11, 2001 Abstract: An apparatus and method are provided for precisely isolating a target lesion in a patient's body tissue, resulting in a high likelihood of"clean" margins about the lesion when it is removed for diagnosis and/or therapy. This approach advantageously will often result in the ability to both diagnose and treat a malignant lesion with only a single percutaneous procedure, with no follow-up percutaneous or surgical procedure required, while minimizing the risk of migration of possibly cancerous cells from the lesion to surrounding tissue or the bloodstream. In particular, the apparatus comprises a biopsy instrument having a distal end adapted for entry into the patient's body, a longitudinal shaft, and a cutting element disposed along the shaft. The cutting element is actuatable between a radially retracted position and a radially extended position. Advantageously, the instrument is rotatable about its axis in the radially extended position to isolate a desired tissue specimen from surrounding tissue by defining a peripheral margin about the tissue specimen. Once the tissue specimen is isolated, it may be segmented by further manipulation of the cutting element, after which the tissue segments are preferably individually removed from the patient's body through a cannula or the like. Alternatively, the specimen may be encapsulated and removed as an intact piece. Excerpt(s): The present invention relates to methods and devices for removing tissue samples, and more specifically to improved instruments and methods for acquiring soft body tissue. It is often desirable and frequently necessary to sample or remove a portion of tissue from humans and other animals, particularly in the diagnosis and treatment of patients with cancerous tumors, pre-malignant conditions, and other diseases or disorders. Typically, in the case of cancer, particularly cancer of the breast, there is a great emphasis on early detection and diagnosis through the use of screening modalities, such as physical examination, and particularly mammography, which is capable of detecting very small abnormalities, often nonpalpable. When the physician establishes by means of a mammogram or other screening modality, such as ultrasound, that suspicious circumstances exist, a biopsy must be performed to capture tissue for a definitive diagnosis as to whether the suspicious lesion is cancerous. Biopsy may be done by an open or percutaneous technique. Open biopsy, which is an invasive surgical procedure using a scalpel and involving direct vision of the target area, removes the entire mass (excisional biopsy) or a part of the mass (incisional biopsy). Percutaneous biopsy, on the other hand, is usually done with a needle-like instrument through a relatively small incision, blindly or with the aid of an artificial imaging device, and may be either a fine needle aspiration (FNA) or a core biopsy. In FNA biopsy, individual cells or clusters of cells are obtained for cytologic examination and may be prepared such as in a Papanicolaou smear. In core biopsy, as the term suggests, a core or fragment of tissue is obtained for histologic examination which may be done via a frozen section or paraffin section. Web site: http://www.delphion.com/details?pn=US06699206__
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Cancer treatments Inventor(s): Dalgleish; Angus George (London, GB), Smith; Peter Michael (London, GB), Sutton; Andrew Derek (London, GB), Walker; Anthony Ian (London, GB) Assignee(s): Onyvax Limited (London, GB) Patent Number: 6,699,483 Date filed: September 7, 2001 Abstract: The invention relates to a product comprised of specific combinations of cell lines intended for use as an allogeneic immunotherapy agent for the treatment of prostate cancer in humans. The heterogeneity of the immunotherapeutic matches the heterogeneity of the antigenic profile in the target prostate cancer and immunises the recipients with many of the potential TAA and TSA which are expressed at various stages of the disease. The invention discloses a vaccine comprising a combination of three different cell lines prepared from primary or metastatic prostate cancer biopsy material. The cell lines are lethally irradiated utilising gamma irradiation at 50-300 Gy to ensure that they are replication incompetent. Excerpt(s): This invention is concerned with agents for the treatment of primary, metastatic and residual cancer in mammals (including humans) by inducing the immune system of the mammal or human afflicted with cancer to mount an attack against the tumour lesion. In particular, the invention pertains to the use of whole-cells, derivatives and portions thereof with or without vaccine adjuvants and/or other accessory factors. More particularly, this disclosure describes the use of particular combinations of whole-cells and derivatives and portions thereof that form the basis of treatment strategy. It is known in the field that cancerous cells contain numerous mutations, qualitative and quantitative, spatial and temporal, relative to their normal, non-cancerous counterparts and that at certain periods during tumour cells' growth and spread a proportion of these are capable of being recognised by the hosts' immune system as abnormal. This has led to numerous research efforts world-wide to develop immunotherapies that harness the power of the hosts' immune system and direct it to attack the cancerous cells, thereby eliminating such aberrant cells at least to a level that is not life-threatening (reviewed in Maraveyas, A. & Dalgleish, A. G. 1977 Active immunotherapy for solid tumours in vaccine design in The Role of Cytokine Networks, Ed. Gregoriadis et al., Plenum Press, New York, pages 129-145; Morton, D. L. and Ravindranath, M. H. 1996 Current concepts concerning melanoma vaccines in Tumor Immunology--Immunotherapy and Cancer Vaccines, ed. Dalgleish, A. G. and Browning, M., Cambridge University Press, pages 241-268. See also other papers in these publications for further detail). Efforts to stimulate the immune system non-specifically date back over a century to the pioneering work of William Coley (Coley, W. B., 1894 Treatment of inoperable malignant tumours with toxins of erisipelas and the Bacillus prodigosus. Trans. Am. Surg. Assoc. 12: 183). Although successful in a limited number of cases (e g. BCG for the treatment of urinary bladder cancer, IL-2 for the treatment of melanoma and renal cancer) it is widely acknowledged that non-specific immunomodulation is unlikely to prove sufficient to treat the majority of cancers. Whilst non-specific immune-stimulants may lead to a general enhanced state of immune responsiveness, they lack the targeting capability and also subtlety to deal with tumour lesions which have many mechanisms and plasticity to evade, resist and subvert immune-surveillance. Web site: http://www.delphion.com/details?pn=US06699483__
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Combination of a vaginal speculum with a single-lens colposcope Inventor(s): Borodulin; German (583 46th Ave., San Francisco, CA 94121), Diokno; Ananias (480 Hillspur Rd., Ann Arbor, MI 48105), Shkolnik; Alexander (485 Dartmouth Ave., San Carlos, CA 94070) Assignee(s): none reported Patent Number: 6,712,761 Date filed: June 4, 2002 Abstract: The invention relates to a combination of a vaginal speculum with a singlelens colposcope for use in a screening process for detecting mucosal abnormalities of cervical intraepithelial neoplasia or invasive cancer, e.g., in the vaginal cavity or on the external parts of the genitalia, as an addition to a Pap Smear screening process. The vaginal speculum is identical to a conventional speculum in its shape, dimensions, and function and differs from a conventional instrument only by having on the inner surface of the lower blade a small projection with a slot for guiding a single-loop colposcope. The latter consists of a tubular rod that can be slidingly inserted into the aforementioned slot and support on its distal end an optical lens. The lens may have a central opening for insertion of surgical instruments, e.g., a biopsy sampler. The proximal end of the tubular rod may support a rubber bulb for suction fluids from the distal end of the lower blade via the tubular rod. In use, the colposcope is inserted into the vaginal speculum through the guide slot so that the physician can manipulate with the colposcope by moving it in axial direction for focusing the lens and by turning the rod to the left or to the right for observing an area of interest. The vaginal speculum and the colposcope can be molded from plastic and can be disposable. Excerpt(s): The present invention relates to the field of medical devices for conducing close range physical medical examinations, in particular to colposcopes used for conducting gynecological and urological examinations. Two methods are used for earlier detection of cervical cancer and pre-cancer: cytology and colposcopy. Cytology is a screening method that is practical and economical, while colposcopy is a diagnostic method for clinical diagnosis of patients with abnormal cytology. Each method has its practical limitations and strength in cancer detection, and both methods complement each other. Currently a standard gynecological exam comprises the use of a speculum, visual examination of the vaginal interior cavity and related structures without any use of magnification, pulpation of the pelvic region and a Pap smear. If the abnormalities are not detected visually, they may be detected by the Pap smear or Pap test. The word "Pap" is short for Papanicolaou, which is the last name of the doctor who studied earlier detection of changing cervical cells. When conducting Pap smear screenings, the gynecologist gently scrapes and collects exfoliated cells from the surface of the cervix by a thin wooden stick and a tiny brush and places them on slides that are sent to a cytologist for further examination. Web site: http://www.delphion.com/details?pn=US06712761__
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Dual mode real-time screening and rapid full-area, selective-spectral, remote imaging and analysis device and process Inventor(s): Deweert; Michael James (Kailua, HI), Seiple, Jr.; Robert Benton (Kailua, HI), Sweat; Joseph Allen (Honolulu, HI), Walton; David George Shibasaki (Honolulu, HI), Wolters; Rolf Holger (Honolulu, HI) Assignee(s): STI Medical Systems, Inc. (Honolulu, HI) Patent Number: 6,678,398 Date filed: March 12, 2003 Abstract: The invention provides a device and process for real-time screening of areas that can be identified as suspicious either through image segmentation utilizing image processing techniques or through treatment with an exogenous fluorescent marker that selectively localizes in abnormal areas. If screening detects a suspicious area, then the invention allows acquiring of autofluorescence images at multiple selected narrow differentiating spectral bands so that a "virtual biopsy" can be obtained to differentiate abnormal areas from normal areas based on differentiating portions of autofluorescence spectra. Full spatial information is collected, but autofluorescence data is collected only at the selected narrow spectral bands, avoiding the collection of full spectral data, so that the speed of analysis is increased. Excerpt(s): This invention relates to a device and process that provides, in a screening mode, real-time screening and remote imaging, and in an analysis mode, rapid full-area, selective-spectral remote imaging and analysis. More specifically, this invention relates to a device for allowing real-time detection and rapid remote analysis of surfaces with differentiating spectral properties, such as potentially cancerous regions in the cervix, intestine, lungs or other organs. Cancers, especially cancers in the intestine, cervix, lungs, and other hollow organs, need to be detected early for effective treatment. For example, intestinal cancers typically start with polyps, either protruding (pedunculated tubular adenomas) or flat (sessile villous adenomas). These polyps sometimes convert into cancer. Therefore, the detection or removal of polyps by colonoscopy significantly reduces the risk of getting colon cancer. Traditionally, polyps are detected using devices that allow a physician to visually examine the interior of the intestine. However, because of the large interior surface area of the intestine, such examinations need to be carried out at a rapid rate so that the maximum area of the intestine can be examined in a minimum amount of time. Further, the amount of time for such examinations must be minimized in order to minimize the expenses and physical impact of such examinations. It is also more difficult to detect flat polyps (sessile villous adenomas) with such examinations. Two major types of procedures for intestinal examination are sigmoidoscopy and colonoscopy. In these procedures, a device for viewing the interior of a hollow organ, usually an endoscope, is inserted into the intestine through the anus. The endoscope usually includes input from a light source and includes lenses at the end of a long flexible cable. An imaging bundle of coherently bundled optical fibers is usually provided inside the cable to transmit an image with a resolution determined by the number of fibers in the bundle. The field of view of an endoscope can be 45 to 140 degrees, depending on the lenses selected. Some endoscopes also have a biopsy channel in the cable that allows the examining physician to extract a tissue sample, such as a portion of a polyp, for later analysis, such as by a biopsy (or even to extract an entire polyp). In sigmoidoscopy, the patient is conscious during the examination, and therefore, the time for the examination must be minimized to minimize the patient's discomfort during the procedure. Further, sigmoidoscopy does not screen the entire length of the intestine because a sigmoidoscope does not pass beyond a 120-degree bend
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in the intestine called the left colic (splenic flexure). In a colonoscopy, the entire length of the intestine can be screened, but the patient must be fully anesthetized, which introduces all the attendant risks of anesthetization. Traditional visual analysis of polyps and other colonic lesions requires training and experience. Because polyps are small, and not all polyps are cancerous, it is helpful to somehow mark pre-cancerous polyps or other abnormal tissues to enhance viewing and detection while screening. It is desirable to reduce the overall number of biopsies because there is an increased risk of morbidity with each additional biopsy. Web site: http://www.delphion.com/details?pn=US06678398__ •
Endoscope with objective lens drive mechanism Inventor(s): Mitsumori; Naotake (Saitama, JP) Assignee(s): Fuji Photo Optical Co., Ltd. (Saitama, JP) Patent Number: 6,641,530 Date filed: April 30, 2002 Abstract: An endoscope with an objective lens drive mechanism for an objective lens system. The insertion instrument of the endoscope is provided with an angle section on the proximal side of the rigid tip end section for flexibly bending at least in upward and downward directions. Provided on an end face of a casing of a rigid tip end section of the insertion instrument are at least a illumination window, an observation window and an exit opening of a biopsy channel. An objective lens system includes a fixed lens mounted on a fixed lens frame, and at least a movable lens mounted on a movable lens frame. For rationally laying out internal components, the interior of the casing of the rigid tip end section is divided into right and left subsections along a center line of upward and downward flexures of the angle section. The observation window is located across the center line of upward and downward flexures to occupy part of both of the right and left subsections. The exit opening of the biopsy channel is located in one of the right and left subsections, while a lens drive shaft of the objective lens drive mechanism is located in the other one of the right and left subsections. An offset arm which is extended out from the movable lens frame is engaged with the lens drive shaft through a translating means which converts forward and reverse rotations of the lens drive shaft into back and forth linear movements of the movable lens frame. Connect to the lens drive shaft is a control cable which is constituted by a flexible transmission shaft encased in a flexible sleeve, the fore end of which is fixedly connected to the casing of the rigid tip end section. Excerpt(s): This invention relates to an endoscope for medical use, incorporating an objective lens drive mechanism in association with an optical objective lens system on its insertion instrument, and more particularly to an endoscope with an objective lens drive mechanism permitting to shift the position of at least one lens element of an optical objective lens system in the direction of its optical axis by remote control to vary at least observation depth, image magnification scale or view field angle. In general, endoscopes which are used for medical purposes are largely constituted by a manipulating head assembly to be gripped by an operator to control the operation of the endoscope, an insertion instrument extended out on the front side of the manipulating head assembly for insertion into a body cavity, and a universal cable led out from the manipulating head assembly for connection to a light source. In terms of construction and function, the insertion instrument is composed of a rigid tip end section, an angle section and a flexible rod section, from its fore distal end to proximal end. The flexible rod section,
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which occupies a major portion of the entire length of the insertion instrument, is arranged to be flexible in arbitrary directions along a path of insertion which may contain bends. The rigid tip end section is provided with at least an illumination window and an observation window, along with an outlet opening of a biopsy instrument channel which is usually provided in the insertion instrument for the purpose of insertion of forceps or other instruments. The angle section is flexible by remote control from the side of the manipulating head assembly. Accordingly, the rigid tip end section can be turned into an arbitrary direction by bending the angle section by remote control. A light emitting end of a light guide, which consists of a bundle of fiber optics, is disposed in the illumination window on the rigid tip end section of the insertion instrument. The light guide is passed through the insertion instrument and assembled into the universal cable which is led out from the manipulating head assembly as mentioned above. Further, an objective lens system is mounted on an image pickup assembly block within the rigid tip end section of the insertion instrument, along with a solid-state image sensor device which is located at the focus of the objective lens system. Normally, the image pickup assembly block is located substantially at a central position in a cross-sectional area of the rigid tip end section. On the other hand, it is usually the case that an illumination window is provided at one or a plural number of positions in the vicinity of an observation window at the distal end of the image pickup assembly block. Accordingly, the center of observation view field is located substantially at a central position of the insertion instrument, and the illumination window or windows are arranged to irradiate the entire view field including center portions thereof. Web site: http://www.delphion.com/details?pn=US06641530__ •
Excisional biopsy devices and methods Inventor(s): Lee; Roberta (Redwood City, CA), Vetter; James W. (Portola Valley, CA) Assignee(s): Rubicor Medical, Inc. () Patent Number: 6,702,831 Date filed: January 31, 2002 Abstract: An excisional biopsy device includes a tubular member having a window near a distal tip thereof; a cutting tool, a distal end of the cutting tool being attached near the distal tip of the tubular member, at least a distal portion of the cutting tool being configured to selectively bow out of the window and to retract within the window; and a tissue collection device externally attached at least to the tubular member, the tissue collection device collecting tissue excised by the cutting tool as the biopsy device is rotated and the cutting tool is bowed. An excisional biopsy method for soft tissue includes the steps of inserting a generally tubular member into the tissue, the tubular member including a cutting tool adapted to selectively bow away from the tubular member and an external tissue collection device near a distal tip of the tubular member; rotating the tubular member; selectively varying a degree of bowing of the cutting tool; collecting tissue severed by the cutting tool in the tissue collection device; and retracting the tubular member from the soft tissue. The tubular member may include an imaging transducer and the method may include the step of displaying information received from the transducer on a display device and the step of varying the degree of bowing of the cutting tool based upon the displayed information from the imaging transducer. Alternatively, the imaging transducer may be disposed within a removable transducer core adapted to fit within the tubular member.
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Excerpt(s): The present invention pertains to the field of soft tissue excisional biopsy devices and methods. In particular, the present invention relates to the field of devices and methods for excising suspicious lesions from soft tissue, such as breast tissue. Breast cancer is a major threat and concern to women. Early detection and treatment of suspicious or cancerous lesions in the breast has been shown to improve long term survival of the patient. The trend is, therefore, to encourage women not only to perform monthly self-breast examination and obtain a yearly breast examination by a qualified physician, but also to undergo annual screening mammography commencing at age 40. Mammography is the only screening modality available today that can detect small, nonpalpable lesions. These nonpalpable lesions may appear as opaque densities relative to normal breast parenchyma and fat or as clusters of microcalcifications. The conventional method for diagnosing, localizing and excising nonpalpable lesions detected by mammography generally involves a time-consuming, multi-step process. First, the patient goes to the radiology department where the radiologist finds and localizes the lesion either using mammography or ultrasound guidance. Once localized, a radio-opaque wire is inserted into the breast. The distal end of the wire may include a small hook or loop. Ideally, this is placed adjacent to the suspicious area to be biopsied. The patient is then transported to the operating room. Under general or local anesthesia, the surgeon performs a procedure called a needle-localized breast biopsy. In the needlelocalized breast biopsy, the surgeon, guided by the wire previously placed in the patient's breast, excises a mass of tissue around the distal end of the wire. The specimen is sent to the radiology department where a specimen radiograph is taken to confirm that the suspicious lesion is contained within the excised specimen. Meanwhile, the surgeon, patient, anesthesiologist and operating room staff, wait in the operating room for confirmation of that fact from the radiologist before the operation is completed. The suspicious lesion should ideally be excised in toto with a small margin or rim of normal breast tissue on all sides. Obtaining good margins of normal tissue is extremely dependent upon the skill and experience of the surgeon, and often an excessively large amount of normal breast tissue is removed to ensure that the lesion is located within the specimen. This increases the risk of post-operative complications, including bleeding and permanent breast deformity. As 80% of breast biopsies today are benign, many women unnecessarily suffer from permanent scarring and deformity from such benign breast biopsies. Web site: http://www.delphion.com/details?pn=US06702831__ •
Firing mechanism for use in a surgical biopsy device Inventor(s): Garrison; William A. (Springdale, OH), Stephens; Randy R. (Fairfield, OH) Assignee(s): Ethicon Endo-Surgery, Inc. (Cincinnati, OH) Patent Number: 6,730,044 Date filed: September 28, 2001 Abstract: The invention described herein is an image-guided, vacuum assisted, percutaneous, coring, cable driven breast biopsy instrument which may be conveniently mounted to an x-ray machine. The biopsy instrument described herein incorporates incorporates a firing mechanism to rapidly advance the biopsy probe into the breast. Excerpt(s): The present invention relates, in general, to an improved surgical biopsy device and, more particularly, to an improved firing mechanism for use in a surgical biopsy device. Generally there are two ways to percutaneously obtain a tissue sample from within the body, aspiration or core sampling. Aspiration of the tissue through a
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fine needle requires the tissue to be fragmented into small enough pieces to be withdrawn in a fluid medium. Application is less intrusive than other known sampling techniques, but one can only examine cells in the liquid (cytology) and not the cells and the structure (pathology). In core biopsy, a core or fragment of tissue is obtained for histologic examination which may be done via a frozen or paraffin section. The type of biopsy used depends mainly on various factors and no single procedure is ideal for all cases. A number of core biopsy instruments which may be used in combination with imaging devices are known. Spring powered core biopsy devices are described and illustrated in U.S. Pat. Nos. 4,699,154, 4,944,308, and Re. 34,056. Aspiration devices are described and illustrated in U.S. Pat. Nos. 5,492,130; 5,526,821; 5,429,138 and 5,027,827. Web site: http://www.delphion.com/details?pn=US06730044__ •
Guide and position monitor for invasive medical instrument Inventor(s): Chin; Donald (Palo Alto, CA), Lin; Shengtz (Cupertino, CA), Maroc; Karen D. (San Jose, CA), Wang; Shih-Ping (Los Altos, CA), Zhang; Siqing (Sunnyvale, CA) Assignee(s): U-Systems, Inc. (San Jose, CA) Patent Number: 6,695,786 Date filed: March 18, 2002 Abstract: An instrument guide is described for mounting an invasive instrument such as a biopsy needle to an imaging probe, controlling its position, monitoring its position, and/or predictively displaying its position on a user display of the medical imaging system. A plurality of substantially rigid segments are hingeably connected to the probe, to an instrument handle, and to each other such that movement of the biopsy needle is restricted to within the imaged plane. However, substantial freedom of movement within the imaged plane is provided such that the instrument may be inserted into the patient over a wide range of angles. In one preferred embodiment, angle detectors are provided at each segment intersection and measurements provided for computing and displaying the instrument position and orientation on the user display. The instrument guide/position monitor is preferably made with low-cost components such that it is disposable after a single use. A predictive user display is provided in which the throw of a spring-loaded instrument is shown on the user display, the throw corresponding to the space that the instrument will occupy after a spring trigger is activated. Excerpt(s): This patent specification relates to medical procedures such as ultrasoundassisted biopsies in which an invasive medical instrument such as a biopsy needle is guided by a medical imaging system such as an ultrasound system. More particularly, it relates to a low-cost apparatus for mounting the instrument to an imaging probe, controlling its position, monitoring its position, and/or predictively displaying its position on a user display of the medical imaging system. Ultrasound imaging systems have become increasingly popular for use in medical applications because they are noninvasive, easy to use, capable of real-time operation, and do not subject patients to the dangers of electromagnetic radiation. Instead of electromagnetic radiation, an ultrasound imaging system transmits sound waves of very high frequency (e.g., 1 MHz to 15 MHz) into the patient and processes echoes from structures in the patient's body to derive and display information relating to these structures. Although the preferred embodiments are described infra with respect to an ultrasound imaging environment, it is to be appreciated that they are also applicable in the context of other medical imaging environments including computerized tomography (CT), magnetic resonance imaging (MRI), and other environments. Among other useful applications, ultrasound imaging
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systems are used in invasive surgical procedures such as biopsies. In such a use, the ultrasound imaging system is used to locate a region of interest in the patient, such as a tumor, and to assist the doctor or other medical professional (hereinafter "user") in guiding a biopsy needle to the tumor. As known in the art, ultrasound imaging systems generally only provide an image of a single plane within the patient as determined by the position and orientation of the ultrasound probe head. In particular, the imaged plane is usually a plane defined by the intersection of two lines, the first line being along a transducer array surface of the probe head, the second line being perpendicular to the first line along a center axis of the probe head. It is necessary to keep the biopsy needle positioned within the imaged plane in order for it to remain visible on the ultrasound monitor during the procedure. Web site: http://www.delphion.com/details?pn=US06695786__ •
Imageable biopsy site marker Inventor(s): Burbank; Fred H. (San Juan Capistrano, CA), Forcier; Nancy (Laguna Niguel, CA), Jones; Michael L. (Capistrano Beach, CA), Lubock; Paul (Laguna Niguel, CA) Assignee(s): SenoRx, Inc. (Aliso Viejo, CA) Patent Number: 6,662,041 Date filed: October 31, 2001 Abstract: A biopsy site marker comprises small bodies or pellets of gelatin which enclose substantially in their interior a radio (X-ray) opaque object. The gelatin pellets are deposited into the biopsy site, typically a cylindrical opening in the tissue created by the recent use of a vacuum assisted large core biopsy device, by an applicator device that includes an elongated cylindrical body that forms a flexible tube and a piston slidable in the tube. One end of the tube is placed into the biopsy site. Typically, several gelatin pellets, only some of which typically do, but all of which may contain the radio opaque object, are deposited sequentially into the site through the tube. The radio opaque objects contained in the gelatin bodies are of a non-biological configuration and readily identifiable as man -made object, so that in observation by typical mammography equipment they do not assume the shape of a line, whereby they are readily distinguishable from granules and lines of calcification. Excerpt(s): The present invention is in the field of markers to be employed at biopsy sites to permanently mark the site, and to methods and apparatus for applying the permanent marker. More particularly, the present invention relates to a marker that is optimally adapted for marking biopsy sites in human breast tissue with permanently placed markers that are detectable by X-ray. In modern medical practice small tissue samples, known as biopsy specimens, are often removed from tumors, lesions, organs, muscles and other tissues of the body. The removal of tissue samples may be accomplished by open surgical technique, or through the use of a specialized biopsy instruments such as a biopsy needle. A well known state-of-the-art instrument that is often used in connection with the practice of the present invention is known as the "vacuum assisted large core biopsy device". After a tissue sample has been removed, it is typically subjected to diagnostic tests or examinations to determine cytology, histology, presence or absence of chemical substances that act as indicators for disease states, or the presence of bacteria or other microbes. The above mentioned and other diagnostic tests and examinations per se are well known in the art and need not be described here. It is sufficient to note that the information obtained from these
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diagnostic tests and/or examinations is often of vital importance for the well-being of the patient and is used to make or confirm diagnoses and often to formulate treatment plans for the patient. As is known, obtaining a tissue sample by biopsy and the subsequent examination are frequently, almost invariably, employed in the diagnosis of cancers and other malignant tumors, or to confirm that a suspected lesion or tumor is not malignant, and are frequently used to devise a plan for the appropriate surgical procedure or other course of treatment. Web site: http://www.delphion.com/details?pn=US06662041__ •
Method and apparatus for sonographic examination, biopsy, and excision Inventor(s): Dubinsky; Theodore J. (7409 - 34th Ave. NW., Seattle, WA 98117) Assignee(s): none reported Patent Number: 6,669,643 Date filed: October 13, 2000 Abstract: Method and apparatus for internal examination of human and other subjects employing special catheters and biopsy wires, in combination with sonographic or fluoroscopic transducers, to provide unprecedented accuracy, economy, and efficiency in internal examination, diagnosis, biopsy, and surgical removal of lesions, tumors, polyps, etc. from bodies. In one aspect the invention provides an apparatus for use in combination with a sonographic transducer for examination and performing biopsies within a vaginal and uterine chamber of a human female and other bodies, whereby the apparatus is comprised of a substantially tubular catheter and any of a wide variety of biopsy devices adapted for disposition on or within the catheter. In another aspect, the invention provides a method of using sonographic or fluoroscopic imaging in combination with the apparatus to examine the cavities under study and to guide the apparatus during a biopsy procedure. Excerpt(s): The invention relates to method and apparatus for sonographic or fluoroscopic examination, biopsy, and excision; more particularly, it relates to method and apparatus for sonographic examination, biopsy, and excision within multichambered cavities of human and other bodies. It is well established that the examination of body cavities is an important part of human and animal health care. Through examination of the interior of body cavities a wide variety of undesirable health conditions may be diagnosed and treated. For example, the examination of the interior of human and animal mouths for rotting and other conditions in teeth has long been practiced. A more difficult proposition, however, has been the examination of more remote or obstructed body cavities. For example, it has only recently become possible to examine the uterus of a human female without cutting the woman open and removing it. Moreover, a survey of the state of the art reveals that there is room for much improvement in the examination and treatment of body cavities, including the retrieval of biopsy samples. An excellent example of the need for improvement in procedures and apparatus for the examination of interior body cavities is the current state of the art in uterine examination and biopsy. It has been shown that peri-and postmenopausal vaginal bleeding (PMB) is one of the most frequent reasons for postmenopausal women to seek medical attention. In the United States, such bleeding accounts for approximately 5% of all gynecologic visits; and conservative estimates predict that over the next ten years at least one million women a year within the U.S. will develop PMB. Historically, women found to suffer from PMB were subjected to hysterectomies: the complete surgical removal of the uterus. As in the case of any major
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surgery, however, hysterectomy has associated risks. Yet at one time hysterectomy was the most commonly performed surgical procedure in the United States. Web site: http://www.delphion.com/details?pn=US06669643__ •
Method for detecting and excising nonpalpable lesions Inventor(s): Harms; Steven E. (Little Rock, AR), Klimberg; V. Suzanne (Little Rock, AR), Korourian; Sohelia (Little Rock, AR) Assignee(s): University of Arkansas (Little Rock, AR) Patent Number: 6,714,808 Date filed: October 3, 2001 Abstract: A novel method of hematoma-directed ultrasound guided excisional breast biopsy is disclosed. In one aspect of the inventon, the hematoma is produced by an injection of the patient's own blood into a pre-selected area to target a lesion. Detection of the targeted lesion and hematoma is achieved with MRI. In a second aspect of the invention, the hematoma is produced by stereotactic core needle breast biopsy in a preselected area, and the targeted lesion and hematoma are detected using intraoperative ultrasound. The method avoids many of the disadvantages associated with traditional needle localized breast biopsy. The method can also be used to guide the excision of lesions visualized by MRI, ultrasound, mammography, PET scanning, and scintimammography. The method may be used in any organ and, in particular, the breast. Excerpt(s): The present invention relates generally to a method for detecting and excising nonpalpable lesions and, more particularly, to a hematoma-directed ultrasound guided excisional breast biopsy. Increased screening mammography has led to over 1,000,000 breast biopsies performed yearly in the United States. An increasing number of these biopsies are for nonpalpable mammographic abnormalities and less than onethird are visible with ultrasound. Available options for biopsy of these mammographic abnormalities have included needle localization excisional breast biopsy (NLBB) or percutaneous stereotactic core needle breast biopsy (SCNBB). Magnetic resonance imaging (MRI) of the breast has allowed for the visualization of lesions previously undetected by mammography. Despite the availability of MRI guided needle localization techniques at medical institutions, the patient is still subjected to the disadvantages and complications inherent to this method of biopsy. Although NLBB most often results in the successful removal of the targeted lesion in mammographically detected lesions, the miss rate varies from 0 to 22% [Snider HC et al., Intraoperative ultrasound localization of nonpalpable breast lesions, Ann Surg Oncol 6(3):308-314 (1999); Rissanen T J et al., Wire localized biopsy of breast lesions: a review of 425 cases found in screening or clinical mammography, Clin Radiol 47:14-22 (1993); Hasselgren P O et al., Breast biopsy with needle localization: accuracy of specimen x-ray and management of missed lesions, Surgery 114:836-42 (1993); and Homer M J et al., Prebiopsy needle localization: methods, problems, and expected results, Radiol Clin North Am 30(1):139-153 (1992)]. The rate is unknown for MRI NLBB, where even thinner wires are used and where the technology is not universally available. Web site: http://www.delphion.com/details?pn=US06714808__
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Method for stimulating an immune response Inventor(s): Cezayirli; Cem (801 Princeton Ave. Suite 310, Birmingham, AL 35211), Silvers; Mel (18970 NE. 21st Ave., North Miami Beach, FL 33179) Assignee(s): none reported Patent Number: 6,645,487 Date filed: December 20, 2000 Abstract: A method is described whereby dendritic cells derived from the CD34+ and CD 34-hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection. Excerpt(s): In recent years there have been numerous advances in the level of understanding of how cancer cells grow inside a host. Generally, it is known that where a tumor or cancer becomes manifest, either there is a deficiency in the host's immune system and/or the tumor cells secrete or express agents which block the normal response of the host's immune system. In any event, there is a failure on the part of the host's immune system to recognize the presence of the cancer cell as "non-self". Because of this failure, the tumor cell and its progeny are allowed to grow without the benefit of predatory attack from the host's immune system cells which are normally responsible for detection of abnormal conditions. Primarily, the immune cells responsible for such predatory attack are the white blood cells of the CD34 lineage including the lymphocyte-activated killer macrophages and the T8 killer cells. Cells derived from CD34 lineage naturally become differentiated to ten or more mature cell types dedicated to specific functions. The functionality is believed to be determined by factors, such as cytokines, leading to the next differentiated stage. Although seemingly much is known of specific hematopoietic cells which have become differentiated into identifiable discrete cell types, little is known about the physiologic control mechanisms involved in such differentiation process. Thus, contemporary research has centered primarily on examination of specifically known cell types and the cell surface "markers" recognizable at each such differentiation stage. Conspicuously lacking in the art has been clearly useful information or understanding of physiological events taking place within the cells as they metamorphosized from one state to the next differentiated state. Consistent with the current state of understanding such cell differentiation is the methodology utilized by leading physicians and researchers in treatment protocols for cancerous diseases. Over the past several decades, cancer treatment methodologies have centered on conventional therapies such as surgical excision, radiation, and the injection of potent chemical agents. Such methodologies have well recognized limitations and have, in many cases, been proved to cause much additional pain and suffering to the patient as well as unreliable long-term effectiveness. Web site: http://www.delphion.com/details?pn=US06645487__
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Modular biopsy and microwave ablation needle delivery apparatus adapted to in situ assembly and method of use Inventor(s): Bush; M. Elizabeth (Fremont, CA), Moorman; Jack W. (Los Gatos, CA) Assignee(s): Vivant Medical, Inc. (Mountain View, CA) Patent Number: 6,652,520 Date filed: October 18, 2001 Abstract: A modular biopsy, ablation and track coagulation needle apparatus is disclosed that allows the biopsy needle to be inserted into the delivery needle and removed when not needed, and that allows an inner ablation needle to be introduced and coaxially engaged with the delivery needle to more effectively biopsy a tumor, ablate it and coagulate the track through ablation while reducing blood loss and track seeding. The ablation needle and biopsy needle are adapted to in situ assembly with the delivery needle. In a preferred embodiment, the ablation needle, when engaged with the delivery needle forms a coaxial connector adapted to electrically couple to an ablating source. Methods for biopsying and ablating tumors using the device and coagulating the track upon device removal are also provided. Excerpt(s): The present invention relates generally to a modular biopsy, ablation and delivery needle apparatus that allows a biopsy needle to be inserted into a delivery needle, and, absent the biopsy needle, allows an inner ablation needle to be introduced and engaged with the delivery needle to form a microwave antenna. The present invention also relates to methods for biopsying and ablating tumors and coagulating the insertion track using the modular apparatus. In the U.S., the lifetime chance of developing an invasive cancer is 46% for men and 38% for women. Cancer is the second leading cause of death in the U.S. and is a major cause of death worldwide. In the U.S. in 1998, there were an estimated 564,800 deaths due to cancer with 1,228,600 new cases of invasive cancer diagnosed. Over 40% of the deaths are associated with primary and metastatic liver cancer. Outside the U.S., primary liver cancer (hepatocellular carcinoma) accounts for one of the largest cancer-related mortalities in the world (about 1,250,000 per year) in adults. In Japan, liver cancer is the third most common cause of death in men. Web site: http://www.delphion.com/details?pn=US06652520__
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MRI compatible surgical biopsy device Inventor(s): Huitema; Thomas W. (Cincinnati, OH), Pyzoha; Jessica M. (Cincinnati, OH), Vander Wende; James W. (Woodstock, VT) Assignee(s): Ethicon Endo-Surgery, Inc. (Cincinnati, OH) Patent Number: 6,626,849 Date filed: December 12, 2001 Abstract: A biopsy device which is compatible for use with a magnetic resonance imaging machine. The device includes a non-metallic elongated substantially tubular needle having a distal end for insertion within tissue, a proximal end, and a longitudinal axis therebetween. The needle includes right and left members on either side of the longitudinal axis, where the right and left members each have upper and lower ends including a series of alternating male and female portions. The male portions of the right member mate with the female portions of the left member, and the male portions of the
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left member mate with the female portions of the right member to securely attach the two members together. The device further includes a port on the elongated needle for receiving a tissue sample. Excerpt(s): The present invention relates, in general, to devices for tissue sampling and, more particularly, to improved biopsy probes for acquiring subcutaneous biopsies and for removing lesions. Generally there are two ways to percutaneously obtain a portion of tissue from within the body, by aspiration or by core sampling. Aspiration of the tissue through a fine needle requires the tissue to be fragmented into small enough pieces to be withdrawn in a fluid medium. The method is less intrusive than other known sampling techniques, but one can only examine cells in the liquid (cytology) and not the cells and the structure (pathology). In core sampling, a core or fragment of tissue is obtained for histologic examination, genetic tests, which may be done via a frozen or paraffin section. The type of biopsy used depends mainly on various factors present in the patient, and no single procedure is ideal for all cases. However, core biopsies seem to be more widely used by physicians. Recently, core biopsy devices have been combined with imaging technology to better target the lesion. A number of these devices have been commercialized. One such commercially available product is marketed under the trademark name MAMMOTOME.TM., Ethicon Endo-Surgery, Inc. An embodiment of such a device is described in U.S. Pat. No. 5,526,822 issued to Burbank, et al., on Jun. 18, 1996, and is hereby incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06626849__ •
MRI-guided interventional mammary procedures Inventor(s): Tsekos; Nikolaos V. (Creve Coeur, MO) Assignee(s): Regents of the University of Minnesota (Minneapolis, MN) Patent Number: 6,675,037 Date filed: September 29, 1999 Abstract: The combination of contrast enhanced magnetic resonance imaging (MRI) and MR-guided subcutaneous core biopsy can be used as a robust approach for the diagnosis and treatment of breast cancer. MRI provides the means to accurately position and monitor interventional procedures such as biopsy, removal of tissue or other transcanular procedures. MRI may also be used in this invention to position and monitor the progress of breast conserving therapies (BCT), such as laser photo-ablation, cryoablation and localized hyperthermia. The general practice of this invention is to provide a remotely controlled apparatus for MR-guided interventional procedures in the breast. The apparatus allows the practice of a method that provides flexibility in conditioning the breast, i.e. orientation and degree of compression, and in setting the trajectory of the intervention. To that end, a robust conditioning/positioning device, fitted with the appropriate degrees of freedom, enhances the efficacy and efficiency of breast interventions by providing the flexibility in planning and executing an appropriate procedure strategy that better suits interventional procedures, either those in current use or yet to be developed. The novelty and potential commercial success of the device originates from its high maneuverability to set and perform the procedure strategy and its adaptability to accommodate an array of interventional probes. Remote control of this device can allow planning the operation and performing the relevant tasks in a short period, for example, within the contrast window provided by a single injection of a contrast agent, and this feature can be operator-independent.
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Excerpt(s): The present invention relates to Magnetic Resonance Imaging-Guided (MRIGuided) medical procedures, particularly MRI-Guided interventional procedures and therapies that are performed on the breasts or mammaries of patients. The diagnosis and treatment of breast cancer is a major health care issue which affects the lives of more than 180,000 women annually, only considering the United States. While, early detection and treatment of breast cancer is a major factor for efficient patient management, there is significant technical space available for developing a highly efficient approach for diagnosing and characterizing breast cancer. Although numerous studies manifest an almost 100% sensitivity of MRI for the detection of breast cancer, the studies also demonstrate a widely varying specificity. These findings result in a patient management dilemma when lesions are detected with MRI and those lesions have not been seen with other gold standard modalities. MRI-Guided biopsy or MRI-Guided wire localization therefore will be important in integrating MRI into breast cancer management. Furthermore, it is reasonable to suggest that the combination of MRI diagnostic imaging, for example contrast agent perfusion, with MRI guided subcutaneous core biopsy may provide an improved method for the detection and characterization of breast cancer. In addition, breast conserving therapies (BCT), such as laser photo-ablation therapy, are under evaluation. These approaches require accurate positioning and monitoring of their effect (e.g. tissue temperature) during insertion and during the actual procedure. Visualization can be achieved in real-time with MRI systems. Thus an apparatus to position interventional devices and monitor their operation under MRI guidance would be likely to improve the success of diagnostic and therapeutic procedures. Several MRguided free-hand or stereotaxic apparatus have been implemented for interventions of the breast, such as preoperative localization, fine needle aspiration biopsy and core biopsy (U. Fischer, et al., "MR Imaging-Guided Biopsy Breast Intervention: Experience with Two Systems" Radiology 192, 876-881, (1994); U. Fischer, et al., "MR-Guided Biopsy of Suspected Breast lesions with a Simple Stereotaxic Add-On Device for Surface Coils" Radiology 200, 651-658 (1996)), (C. K. Cuhl, et al., "Interventional Breast MR Imaging: Clinical Use of a Stereotaxic Localization and Biopsy Device" Radiology 204, 667-675 (1997); S. H. Heywang-Kobrunner, et al., "Prototype Breast Coil for MR-Guided needle Localization" J. Comp. Assist. Tomogr. 18, 876-881 (1994)) and (S. GreensteinOrel, et al., "MR Imaging-Guided Localization and Biopsy of Breast Lesions: initial Experience" Radiology, 193, 97-102 (1994); E. K. Insko, et al., "Multicoil Array for High Resolution Imaging of the Breast" Magn. Reson. Med. 37, 778-784 (1997)). The design and the operation of these devices are tailored for use inside the limited space of an MRI scanner, and a short contrast window (5 to 10 min). Such studies have demonstrated the feasibility of combining MRI, as a diagnostic modality, with MR-guided interventions of the breast. The common features of such devices are: (a) compression of the breast for better fixation, with one or two plates and (b) use of an arrangement of puncture channel (mesh) to correctly place the interventional probe. Despite their success, there are some limitations in these designs, particularly when they are compared with the non-MR stereotaxic devices. First, most of the devices provide compression along a specific orientation, usually medial-lateral, which may not be the optimal one, as for example for transversing the shortest path in the tissue or to reach areas such as the axilla. Second, in most of the devices the probe is directed by means of a mesh, and thus it can be only inserted perpendicular to the compression plates or with a slight "freehand" angulation. This may not be the optimal approach, for example, when attempting to access tissue close to the chest wall, at the axilla or to avoid obstructions such as implants. The two single plate systems have the same limitations and in addition there is the potential for accidental rib puncture or highly invasive operations behind the nipples. The operation of the above devices requires the patient to be removed from the magnet, the probe inserted and then re-imaged, with the possibility that another
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insertion may be required to correct the initial one. This practice increases the length of the operation, and may not be always feasible due to the limited number of allowed injections of contrast material and the short duration of the contrast window. Web site: http://www.delphion.com/details?pn=US06675037__ •
Multiple bit, multiple specimen endoscopic biopsy forceps Inventor(s): Treat; Michael R. (New York, NY) Assignee(s): The Trustees of Columbia University in the City of New York (New York, NY) Patent Number: 6,632,182 Date filed: April 24, 2000 Abstract: A flexible or rigid endoscope biopsy device provides for the taking of multiple biopsy specimens from different sites, and for separating and storing these specimens in a partitioned container. The distal end of this device consists of a grasper which can bite or cut off a bit of tissue. The proximal end of the inner tubing is connected via the handle end of the device to a multi-chambered specimen storage device, which is itself connected to suction. The storage device has several chambers, each of which may be lined up with the inner tubing, by rotating the top of the storage device. After some or all of the storage subpartitions have been filled with specimens, the storage device can be detached from the inner tubing and handle of the device and labeled and sent directly to the pathology lab. Excerpt(s): The invention relates to the field of endoscopic biopsy devices for use in obtaining samples of tissue. More particularly, this invention relates to the field of endoscopic biopsy devices, both flexible and rigid, for use in obtaining multiple samples of tissue without the need for withdrawal and reinsertion of the device during the procedure. An endoscope is a long, narrow instrument which is provided with a means of visualization of the tissue, and also with a means of obtaining tissue biopsy or other manipulations of tissue. The endoscope may be flexible or rigid. The means of visualization may be fiberoptic imaging or by means of a small video chip which is mounted in the distal end of the endoscope. The means of obtaining the biopsy specimen is via a long narrow channel (the "instrument channel" or "biopsy channel") which is within the body of the endoscope. Through this instrument channel a biopsy forceps is passed, which forceps is a long and narrow instrument that can fit through the channel and which has jaws or another cutting or tearing device at its distal end. The jaws device can be actuated by a lever or trigger at the proximal end (the handle) of the biopsy device. The biopsy forceps itself can be rigid in the case of rigid endoscopes or flexible in the case of flexible endoscopes. A typical example of a flexible endoscope would be a colonoscope for examining the colon, a gastroscope for examining the stomach and upper intestine and a bronchoscope for examining the pulmonary bronchi. A typical diameter for the instrument channel of a colonoscope or gastroscope would be around 2.8 mm or slightly larger. For a bronchoscope, since the endoscope itself is narrower, the biopsy channel would be around 2 mm in diameter. Biopsy instruments compatible with these scopes must obviously be narrow enough to comfortably fit in the channel and must also be flexible, since these are all examples of flexible endoscopes. Web site: http://www.delphion.com/details?pn=US06632182__
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Observation window washing device of endoscope Inventor(s): Akiba; Haruo (Ibaraki, JP) Assignee(s): Fuji Photo Optical Co., Ltd. (Saitama, JP) Patent Number: 6,638,214 Date filed: April 2, 2002 Abstract: A notched void portion 29 is provided in a rigid casing block 20 of a rigid tip end section 2c of an endoscopic insertion instrument 2. For spurting a cleaning fluid toward an observation window 11, a cleaning supply passage is constituted by a cleaner nozzle 13, a connector pipe 27 and a flexible tube 26. A cleaner nozzle 13 is partly fitted in the notched void portion 29 which is formed in the rigid casing block 20. The connector pipe 27 is formed in a staggered shape having an angularly bent intermediate pipe section 27c between straight and parallel front and rear pipe sections 27a and 27b. The straight front pipe section 27a is at least partly fitted in the rigid casing block 20 and its fore distal end portion is fitted in the cleaner nozzle 13 over a predetermined length. On the other hand, the flexible tube is fitted on a rear end portion of the straight rear pipe section 27b the position of which is offset radially inward relative to the straight front pipe section 27a by the angularly bent intermediate pipe section 27c to avoid interference with biopsy channel 24, light guides 24 and wiring cable 17 which are threaded through a foremost angle ring 40 of an angle section 2b of the insertion instrument 2. Excerpt(s): This invention relates to a device for cleaning an endoscopic observation window which is provided at a distal end of an elongated insertion instrument of a medical endoscope, and more particularly to an endoscopic observation window cleaning device which is particularly suitable for application to a medical endoscope having a narrow insertion instrument of a reduced diameter for insertion into a body cavity. Generally, endoscopes which are in use in medical fields are largely composed of a manipulating head assembly to be gripped and manipulated by an operator, an elongated insertion instrument extended out on the front side of the manipulating head assembly for insertion into a body cavity, and a universal cable led out from the manipulating head assembly for connecting same to a light source (or to a light source and a processor). The insertion instrument is provided with at least an illumination window and an observation window on a distal end face. It is usually the case that the illumination window is provided either at one or two positions on the distal end face. A diffuser lens is fitted in each illumination window in front of a light emitting end of a light guide which is connected to a light source. On the other hand, an optical objective lens system is fitted in the observation window, and a solid-state image sensor device is located at the focus of the objective lens system. Further, an outlet of a biopsy channel is opened in the distal end face of the insertion instrument. Therefore, when a diseased portion is spotted as a result of an endoscopic examination, forceps or other biopsy or surgical instruments are passed through the biopsy channel and projected into the body cavity to make a necessary treatment. Further, the endoscope is provided with the socalled observation window cleaning device thereby to spurt a cleaning fluid toward the observation window in case it is contaminated with body fluids or the like. Normally, the observation window cleaning device is provided on the distal end face of the insertion instrument, and largely composed of a jet nozzle for spurting a cleaning fluid, a mixture of a cleaning liquid and compressed air, toward the observation window, and a cleaning fluid supply passage which supplies the cleaning fluid to the jet nozzle. The cleaning fluid supply passage is extended through the insertion instrument and into the universal cable via the manipulating head assembly.
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Optical needle guide for ultrasound guided needle biopsy Inventor(s): Paladini; Gianluca (Princeton, NJ), Sauer; Frank (Princeton, NJ) Assignee(s): Siemens Corporate Research, Inc. (Princeton, NJ) Patent Number: 6,702,749 Date filed: July 24, 2002 Abstract: An optical guide for a biopsy needle includes a light projector for producing a line image on a patient's skin surface, wherein the light projector is adapted for mounting on an ultrasound transducer such that the line image corresponds with an intersection of the transducer ultrasound plane with the skin surface. Excerpt(s): The present invention relates to the field of medical biopsy and, more particularly, to needle biopsy. For a typical needle biopsy, a biopsy needle has to be inserted into an anatomical target to remove a tissue sample. Ultrasound guidance using ultrasound imaging is routinely used as, for example, for breast needle biopsy. The real-time ultrasound images allow the operating physician to locate the target and to monitor the needle position. The ultrasound imaging apparatus is well-known and descriptions can be found in articles, texts, and the trade literature. Generally the procedure is performed "in-plane". With the ultrasound transducer being in a position where the target is visible in the image, the insertion point of the needle is chosen on the intersection of the ultrasound plane and the patient's skin surface. The needle is oriented so that it lies in this plane and points towards the target. When the needle is now inserted, it will appear in the ultrasound image, and its progress along its path towards the target can be monitored. Web site: http://www.delphion.com/details?pn=US06702749__
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Over the wire breast biopsy system Inventor(s): Fontenot; Mark G. (229 Marilyn Dr., Lafayette, LA 70503) Assignee(s): none reported Patent Number: 6,716,180 Date filed: March 12, 2002 Abstract: Systems comprising a wire and an excision instrument particularly intended for breast biopsy are provided. The excision instrument has a fixed or attachable blade for taking a sample. Excerpt(s): The present invention relates to method and devices for removing a predetermined amount of breast tissue for the purposes of treatment and/or microscopic examination. Wire needle localization (WNL) is a surgical technique frequently invoked by surgeons to biopsy lesions in the breast discovered as a result of mammography or other breast screening methods. Patients undergoing WNL are placed on a radiographic table usually located in the radiology suite. The breast is placed between two compression plates, arranged moveably in relation to one another, for fixing the breast therebetween. The compression plates have through holes which permit the introduction of a biopsy needle into the breast and proximate to the breast lesion under radiographic guidance. Once the needle is placed in the desired position in
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the breast, a thin, stiff wire with a distal retaining hook is inserted through the lumen of the needle. As the wire emerges from the distal aspect of the needle, the distal hook of the wire engages the breast tissue proximate to the breast lesion. The needle is withdrawn leaving the hook wire proximate to the lesion. The position of the wire relative to the lesion is verified radiographically. Radiographic views of the wire in the breast are taken and brought to the operating so as to allow the surgeon to plan the surgical biopsy procedure. The patient is transferred to the operating room. The surgeon plans his approach to surgically retrieving and adequate tissue specimen after physically examining and reviewing the radiographs of the breast with the wire placed in proximity to the breast lesion. The wire serves as a marker which can be palpated by the surgeon at the time of and during surgery which serves as a marker during surgery. Local anesthetic is administered in and around the proposed surgical area. An incision is made and the surgeon dissects around the wire. During the dissection, the surgeon continuously palpates the location of the wire in order to orient the dissection and determine that amount of tissue to be harvested or biopsied. Web site: http://www.delphion.com/details?pn=US06716180__ •
Perfusion sensitive biopsy extractor Inventor(s): Bowman; Harry Frederick (Needham, MA), Martin; Gregory T. (Cambridge, MA) Assignee(s): Thermal Technologies, Inc. (Cambridge, MA) Patent Number: 6,632,183 Date filed: February 12, 2001 Abstract: A technique for quantifying perfusion and removing a biopsy sample at a site in a living body wherein an instrument having a perfusion sensor is introduced into the body at a site to be investigated to there interrogate the tissue. The biopsy specimen is collected when the perfusion sensor produces a signal indicative of perfused, viable tissue. Excerpt(s): This invention relates to a method and apparatus for quantifying blood flow in tissue and specifically for quantifying blood flow in tissue at a location within the body where therapy or diagnosis is required. The ability to quantify tissue blood flow permits the physician to plan and schedule specific therapies designed for a patient's particular condition. For example, blood flow is a carrier of therapeutic agents throughout the body. The ability to quantify blood flow at a site within the body where drug therapy is required will permit the physician to evaluate the extent to which therapeutic agents introduced into the circulatory system will actually reach and affect the site to be treated. One clinical area in which the current invention is useful is in the treatment of cancer, particularly those cancer cases that are treated non-surgically. Almost all cancers treated non-surgically will undergo therapies whose efficacy is strongly related to tissue and tumor blood flow. A number of anti-cancer agents depend on the circulatory system for delivery to the target tissue. Blood flow, the carrier of therapeutic agents to the tumor, also acts as a carrier of oxygen. Increased blood supply increases tissue oxygenation and the concentration of chemotherapeutic agents. Correspondingly, the concentration of oxygen at the site and the concentration of chemotherapeutic agents are enhancers of the effectiveness of therapies such as radiation therapy and chemotherapy. In the treatment of tumors, various techniques have been used to increase the blood flow and thereby increase the oxygen supply to the site in the tumor being treated. Efforts to increase blood flow to tumors include the use
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of vasoactive drugs, viscosity modifiers and local hyperthermia therapy. In these attempts, circulation is affected systemically but there is always a question of the extent to which circulation in the specific site to be treated is affected. The need to increase blood flow to diseased tissue is associated with a corresponding need to measure or quantify blood flow at the treatment site. Web site: http://www.delphion.com/details?pn=US06632183__ •
Retractable brush for use with endoscope for brush biopsy Inventor(s): Frist; Stephen (Suffern, NY), Rutenberg; Mark (Suffern, NY) Assignee(s): CDx Laboratories, Inc. (Suffern, NY) Patent Number: 6,676,609 Date filed: December 17, 2002 Abstract: A retractable brush structure is attached to a cylindrical rigid rod which in the closed position passes through a channel in an endoscope. After the brush passes through the endoscope, the brush moves against the tissue in order to remove cells from an area under examination. The brush is withdrawn from the endoscope and sample tissue is removed from said brush for examination after it is withdrawn from the endoscope. Excerpt(s): The present invention is directed to a method and apparatus for obtaining transepithelial specimens of body surfaces using a non-lacerating technique. Specifically, the invention is directed to retractable tools such as a brush, used with endoscopes, for sampling epithelium from lesions found from the nose to the throat and in similar body tissues. The invention is also directed to an improved apparatus for nonlacerational testing of lesions that involve the epithelium of the nasopharynx, hypopharynx, pharynx, trachea, larynx, and the upper esophagus. In metaplastic glandular epithelium as in native tissue, the invention using a brush biopsy must be certain to conduct a biopsy not merely a superficial cytology. In squamous epithelium, it is determined that the base membrane is reached and basal cells are being viewed and are included in the brush biopsy. The transepithelial specimen sought to be examined in this C-I-P patent application is metaplastic glandular epithelium. A disaggregated specimen of the whole tissue comprises at least glandular cells plus basement membrane fragments plus elements of the lamina propria will be picked up by the brush biopsy. Such disaggregated specimen is retrieved with the brush biopsy. Web site: http://www.delphion.com/details?pn=US06676609__
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Surgical biopsy instrument Inventor(s): Abrahams; Yusuf ("Lake View", Sandy Lane, Northwood, Middlesex, GB HA6 3ES), George; Samuel (4 Ronneby Close, Weybridge, Surrey, GB KT13 9SB) Assignee(s): none reported Patent Number: 6,730,085 Date filed: August 23, 2001 Abstract: A cervical biopsy instrument comprises a shaft defining a longitudinal axis and having a proximal end and a distal end; an arm extending laterally from the shaft; a cutting portion of cutting wire being supported at an outer end by the arm and being
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inclined relative to the longitudinal axis; and means for adjusting and setting the inclination and/or length of the cutting portion. This enables a single instrument to deal effectively with differently-sized, shaped and positioned cervical lesions, while tailoring the profile of the excision to the lesion concerned.In the embodiments described, two opposed arms support two cutting portions, requiring 180.degree. of angular movement during excision as opposed to the 360.degree. movement of the prior art. The arms are mounted on a carriage for longitudinal adjustment, and can be bent individually to vary their length and hence the width of cut, which may be asymmetric. A centering means such as a collar is provided to ensure accurate centering within patulous cervical canals. Excerpt(s): This invention relates to the surgical biopsy excision of tissues, particularly but not exclusively the excision of abnormal lining in the uterine cervix. Cancer of the uterine cervix, or cervical cancer, usually progresses slowly over an extended period from the first appearance of pre-cancerous abnormalities. With today's sophisticated screening programs involving regular smear testing, colposcopy and so on, this gradual progression presents an opportunity for many patients entirely to avoid cervical cancer if they can benefit from preventative intervention. Even for those who do not, there is a good prognosis if the cancer is detected and treated early enough. Before malignant cells are found, the tissues of the cervix go through changes in which abnormal cells begin to appear, initially on the epithelial tissue on the surface of the cervix. This precancerous condition is known as dysplasia or cervical intraepithelial neoplasia (CIN). Web site: http://www.delphion.com/details?pn=US06730085__ •
Tissue site markers for in VIVO imaging Inventor(s): Burbank; Fred H. (Laguna Niguel, CA), De Santis; Stephen A. (Laguna Niguel, CA), Jones; Michael L. (Capistrano Beach, CA), Louw; Frank (Carlsbad, CA), Lubock; Paul (Laguna Niguel, CA), Quick; Richard L. (Mission Viejo, CA) Assignee(s): SenoRx, Inc. (Aliso Viejo, CA) Patent Number: 6,725,083 Date filed: November 20, 2000 Abstract: The invention is directed biopsy site markers and methods of marking a biopsy site, so that the location of the biopsy cavity is readily visible by conventional imaging methods, particularly by ultrasonic imaging. The biopsy site markers of the invention have high ultrasound reflectivity, presenting a substantial acoustic signature from a small marker, so as to avoid obscuring diagnostic tissue features in subsequent imaging studies, and can be readily distinguished from biological features. The several disclosed embodiments of the biopsy site marker of the invention have a high contrast of acoustic impedance as placed in a tissue site, so as to efficiently reflect and scatter ultrasonic energy, and preferably include gas-filled internal pores. The markers may have a non-uniform surface contour to enhance the acoustic signature. The markers have a characteristic form which is recognizably artificial during medical imaging. The biopsy site marker may be accurately fixed to the biopsy site so as to resist migration from the biopsy cavity when a placement instrument is withdrawn, and when the marked tissue is subsequently moved or manipulated. Excerpt(s): In diagnosing and treating certain medical conditions, it is often desirable to perform a biopsy, in which a specimen or sample of the suspicious tissue is removed for pathological examination, tests and analysis. As is known, obtaining a tissue sample by biopsy and the subsequent examination are typically employed in the diagnosis of
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cancers and other malignant tumors, or to confirm that a suspected lesion or tumor is not malignant. The information obtained from these diagnostic tests and/or examinations is frequently used to devise a therapeutic plan for the appropriate surgical procedure or other course of treatment. In many instances, the suspicious tissue to be sampled is located in a subcutaneous site, such as inside a human breast. Such removal of tissue samples may be accomplished by open surgical technique, or through the use of a specialized biopsy instrument and techniques. To minimize surgical intrusion into patient's body, it is often desirable to insert a small instrument, such as a biopsy needle, into the body for extracting the biopsy specimen while imaging the procedure using fluoroscopy, ultrasonic imaging, x-rays, MRI or any other suitable form of imaging technique. Examination of tissue samples taken by biopsy is of particular significance in the diagnosis and treatment of breast cancer. In the ensuing discussion, the biopsy and treatment site described will generally be the human breast, although the invention is suitable for marking biopsy sites in other parts of the human and other mammalian body as well. Periodic physical examination of the breasts and mammography are important for early detection of potentially cancerous lesions. In mammography, the breast is compressed between two plates while specialized x-ray images are taken. If an abnormal mass in the breast is found by physical examination or mammography, ultrasound may be used to determine whether the mass is a solid tumor or a fluid-filled cyst. Solid masses are usually subjected to some type of tissue biopsy to determine if the mass is cancerous. Web site: http://www.delphion.com/details?pn=US06725083__ •
Vibration assisted needle device Inventor(s): Damadian; Jevan (East Northport, NY), Gelbien; Mark (Levittown, NY), Votruba; Jan (Brookhaven, NY), Votruba; Michael (Ada, MI) Assignee(s): Fonar Corporation (Melville, NY) Patent Number: 6,702,761 Date filed: March 6, 2001 Abstract: A vibration assisted needle device is disclosed for use in medical procedures, such as needle aspiration biopsies. Reciprocation of the needle, such as a biopsy needle, eases the advance of the needle through tissue, penetration of the site of interest and the collection of sample at a site of interest. The device comprises a housing defining a chamber, a needle support external to the chamber for supporting a needle and a mechanism in the chamber for causing reciprocatory motion of the needle support. The needle support is preferably external to the housing. A syringe support may be connected to the housing for supporting a syringe. The reciprocatory mechanism may comprise means for converting rotational motion into reciprocating motion, such as a bearing or a rotor with a circumferential, angled groove on its surface, coupled to the needle support. The bearing or the rotor may be driven by a rotational motor, preferably located outside of the housing, or by a hydraulically driven turbine within the housing. Alternatively, the reciprocatory mechanism means may comprise a stationary solenoid and a movable solenoid for being coupled to the needle. Preferably, a second stationary solenoid is provided and the moving solenoid is between the two stationary solenoids. Energization of the stationary solenoid or solenoids by an alternating current, for example, and energization of the movable solenoid by a direct current, or vice a versa, attracts and repulses the movable solenoid, causing reciprocation of the needle. Methods and systems using the vibration assisted needle device are also disclosed.
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Excerpt(s): A needle device, and more particularly, a biopsy needle device which is driven to vibrate in a direction along the axis of the needle to ease passage of the needle through tissue and the collection of a sample at a site of interest. When an abnormal area of tissue, such as a tumor, is discovered by non-invasive means, a tissue diagnosis is often required in order to determine the appropriate treatment. This requires that an adequate sample of tissue be removed from the patient for histopathological analysis. The tissue may be obtained in a variety of ways, such as surgical excision, fine needle aspiration biopsy or large needle core biopsy. Fine needle aspiration biopsy, using needles with diameters of 20-22 Gauge, is minimally invasive. Typically, a biopsy needle with a stylet is inserted into the abnormal tissue, under the guidance of an imaging modality, such as ultrasound or magnetic resonance imaging ("MRI"). The stylet is then removed. A syringe is attached to the needle, suction is applied through the syringe and then the needle is manually thrust into and out of the tissue to capture and remove cellular material. However, rather than cutting the tissue to enable collection in the needle bore, the thin needle tends to displace the tissue, especially rigid malignant tissue. Therefore, only a small number of cells may be obtained. Even after repeated attempts, a sufficient amount of tissue might not be obtained. Displacement of tissue also alters the frame of reference defined by the imaging modality. Web site: http://www.delphion.com/details?pn=US06702761__ •
Vitro and in vivo models for screening compounds to prevent glucocorticoid-induced bone destruction Inventor(s): Bellido; Teresita (Little Rock, AR), Jilka; Robert L. (Little Rock, AR), Manolagas; Stavros C. (Little Rock, AR), Weinstein; Robert S. (Little Rock, AR) Assignee(s): Board of Trustees of the University of Arkansas (Little Rock, AR) Patent Number: 6,660,468 Date filed: October 7, 1999 Abstract: The present invention demonstrates that glucocorticoid-induced bone disease is due to changes in the birth and death rate of bone cells using a murine model of glucocorticoid excess as well as bone biopsy specimens obtained from patients with glucocorticoid-induced osteoporosis. This invention demonstrates that glucocorticoid administration increases apoptosis of mature osteoblasts and osteocytes and decreases bone formation rate and bone mineral density accompanied by defective osteoblastogenesis and osteoclastogenesis in the bone marrow. Excerpt(s): The present invention relates generally to bone physiology. More specifically, the present invention relates to in vitro and in vivo models for screening compounds to prevent glucocorticoid-induced bone destruction. The adverse effects of hypercortisolism on bone have been recognized for over 60 years (1), but the precise cellular and molecular basis of these changes has remained elusive. Today, the iatrogenic form of the disease has become far more common than Cushing's syndrome and glucocorticoid-induced osteoporosis is now third in frequency following postmenopausal and senile osteoporosis (2). Bone loss due to glucocorticoid excess is diffuse, affecting both cortical and cancellous bone, but has a predilection for the axial skeleton. Spontaneous fractures of the vertebrae or ribs are, therefore, often presenting manifestations of the disorder (3,4). A cardinal feature of glucocorticoid-induced osteoporosis is decreased bone formation (5). In addition, patients receiving long-term glucocorticoid therapy sometimes develop collapse of the femoral head (osteonecrosis), but the mechanism underlying this is uncertain (6). Decreased bone formation, and in
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situ death of isolated segments of the proximal femur suggest that glucocorticoid excess may alter the birth and death of bone cells. Defective osteoblastogenesis has been reported to be linked to reduced bone formation and age-related osteopenia in the SAMP6 mouse (7). Besides the relationship between aberrant osteoblast production and osteoporosis, it has been recently shown that a significant proportion of osteoblasts undergo apoptosis (8), which raises the possibility that the premature or more frequent occurrence of osteoblast apoptosis could contribute to incomplete repair of resorption cavities and loss of bone. Web site: http://www.delphion.com/details?pn=US06660468__
Patent Applications on Biopsy As of December 2000, U.S. patent applications are open to public viewing.9 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 biopsy: •
Apparatus and method for catheter guidance control and imaging Inventor(s): Shachar, Yehoshua; (Santa Monica, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040019447 Date filed: July 15, 2003 Abstract: A system whereby a magnetic tip attached to a surgical tool is detected, displayed and influenced positionally so as to allow diagnostic and therapeutic procedures to be performed rapidly, accurately, simply, and intuitively is described. The tools that can be so equipped include catheters, guidewires, and secondary tools such as lasers and balloons, in addition biopsy needles, endoscopy probes, and similar devices. The magnetic tip allows the position and orientation of the tip to be determined without the use of x-rays by analyzing a magnetic field. The magnetic tip further allows the tool tip to be pulled, pushed, turned, and forcefully held in the desired position by applying an appropriate magnetic field external to the patient's body. A Virtual Tip serves as an operator control. Movement of the operator control produces corresponding movement of the magnetic tip inside the patient's body. Additionally, the control provides tactile feedback to the operator's hand in the appropriate axis or axes if the magnetic tip encounters an obstacle. The output of the control combined with the magnetic tip position and orientation feedback allows a servo system to control the external magnetic field by pulse width modulating the positioning electromagnet. Data concerning the dynamic position of a moving body part such as a beating heart offsets the servo systems response in such a way that the magnetic tip, and hence the secondary tool is caused to move in unison with the moving body part. The tip position and orientation information and the dynamic body part position information are also utilized to provide a display that allows three dimensional viewing of the magnetic tip position and orientation relative to the body part.
9
This has been a common practice outside the United States prior to December 2000.
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Excerpt(s): The present application claims priority from U.S. Provisional Patent Application No. 60/396,302, filed Jul. 16, 2003, titled "CATHETER GUIDANCE CONTROL AND IMAGING APPARATUS AND METHOD," the entire contents of which is hereby incorporated by reference. The present invention relates to systems and techniques for guiding, steering, and advancing invasive medical devices such as catheters and catheter-type devices. In general, catheterization is performed by inserting an invasive device into an incision or a body orifice. Secondary tools such as guidewires and balloons are often advanced along the primary catheter to the area where the medical procedure is to be performed. These procedures rely on manually advancing the distal end of the invasive device by pushing, rotating, or otherwise manipulating the proximal end that remains outside of the body. Real-time x-ray imaging is a common method for determining the position of the distal end of the invasive device during the procedure. The manipulation continues until the distal end reaches the destination area where the diagnostic or therapeutic procedure is to be performed. This technique requires great skills on the part of the operator that can only be achieved after a protracted training period and extended practice. A high degree of manual dexterity is also required. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Apparatus for transcutaneous biopsy of rigid tissues in particular osteomedullary tissue Inventor(s): Burgio, Vito Lelio; (Roma, IT), Casula, Gianfranco; (Rho (Milano), Giusti, Dario; (Roma, IT) Correspondence: William Collard; Collard & Roe, P.C.; 1077 Northern Boulevard; Roslyn; NY; 11576; US Patent Application Number: 20040059252 Date filed: June 27, 2003 Abstract: The apparatus (1) for transcutaneous biopsy of rigid tissues comprises hollow needle means (2) provided with tapered distal end (3), blocking means (10) suitable for being inserted into said hollow needle means (2) in order to block a sample of said tissue at the interior of said hollow needle (2), said blocking means (10) comprising blade means (11; 13), handle means (6) associated with a proximal end of said hollow needle (2), said blocking means (10) is coupled with advancing means (9) suitable for advancing said blocking means (10) inside said hollow needle means (2) between a first rear position and a second forward position. Excerpt(s): The present invention relates to an apparatus for transcutaneous biopsy of rigid tissues, in particular osteomedullary tissue, i.e. an apparatus for taking, from the body of a patient, a sample of said tissue, suitable for being submitted to examination. From the prior art apparatuses are known for transcutaneous biopsy of rigid tissues comprising a needle consisting of a hollow cylinder provided with handle at the proximal end, with the distal end tapered and provided with cutting edge. A hollow, cylindrical rod is suitable for being inserted into the needle, said hollow, cylindrical rod being provided with a small handle at its proximal end and ending, at the distal end, with a curved blade, or a pair of facing, curved blades, separated from each other by a pair of opposed, longitudinal notches. In order to take from the body of the patient a sample of tissue to be analysed, first of all the needle is inserted into the region of the body of the patient, from which the sample is intended to be taken, the needle being inserted with the aid of a mandrel provided with penetrating tip and suitable for being
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inserted into the needle. Once the tip of the needle has reached the region from which the sample must be taken, the mandrel is extracted and the needle is further pushed into the tissue. During this manoeuvre, a cylindrical sample of tissue penetrates into the needle, said sample being still connected with the surrounding tissue at one of its own ends. At this point, the aforementioned hollow, cylindrical rod is inserted into the needle and, during such operation, the end of the rod shaped as a blade, or a pair of opposed blades, interposes between the sample of tissue and the internal wall of the needle. If the end of the hollow, cylindrical rod is shaped as a single, curved blade, the tapered tip of the needle causes a deformation of the blade which is deflected towards the axis of the needle and applies a pressure against the sample of tissue, so as to block it by friction on the internal wall of the needle. When the end of the hollow, cylindrical rod is shaped as a pair of opposed blades, the tapered tip of the needle causes a deforms the blades and press them between the internal surface of the needle and the external surface of the sample of tissue, thus causing a coupling by friction between sample of tissue, cylindrical blades and internal surface of the needle, said coupling blocking the sample of tissue at the inside of the needle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Assessment of liver fibrosis scoring with serum marker algorithms Inventor(s): Arthur, Michael J.; (West Wellow, GB), Becka, Michael; (Ense, DE), Burchardt, Elmar-Reinhold; (Schwerte, DE), Burt, Alastair D.; (Fairmoor Morphet, GB), Gehrmann, Mathias; (Leverkusen, DE), Hennig, Guido; (Koln, DE), Knorr, Andreas; (Erkrath, DE), Kroll, Werner; (Solingen, DE), Pinzani, Massimo; (Scandicci, IT), Schuppan, Detlef; (Bubenreuth, DE), Unger, Sylvia; (Heidelberg, DE), Volker, Michael; (Koln, DE) Correspondence: Bayer Corporation; Law & Patents; 511 Benedict Avenue; Tarrytown; NY; 10591; US Patent Application Number: 20040053242 Date filed: October 7, 2003 Abstract: The present invention concerns a method for diagnosing liver fibrosis wherein two or more diagnostic markers are measured and the measurements are correlated by a mathematic algorithm characterized in that the diagnostic markers are selected from the group N-terminal procollagen III propeptide (PIIINP), Collagen IV/, Collagen VI, Tenascin, Laminin, Hyaluronan, MMP-2, TIMP-1 and MMP-9/TIMP complex. The algorithm can be used to predict the histological score of a liver biopsy. Excerpt(s): Progressive fibrotic diseases of the liver are a major cause of morbidity and mortality throughout the world. Recent scientific advances demonstrate that the pathogenic process of fibrosis in liver is critically dependent on proliferation and activation of hepatic stellate cells (also called lipocytes, fat-storing or Ito cells) which synthesize and secrete excess extracellular matrix proteins (1). Moreover it is evident that this process is common to liver disease of all aetiologies. Of particular importance are chronic viral hepatitis B and C and alcoholic liver disease as well as autoimmune and genetic liver diseases, all of which lead to clinical problems via the common final pathway of progressive liver fibrosis, with the eventual development of cirrhosis. An important concept is the distinction between hepatic fibrosis and cirrhosis. Hepatic fibrosis is a reversible accumulation of extracellular matrix in response to chronic injury in which nodules have not yet developed, whereas cirrhosis implies an irreversible process, in which thick bands of matrix fully encircle the parenchyma, forming nodules.
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Consequently, any therapy must be directed towards patients with reversible disease (fibrosis), which will require early identification and monitoring of those at risk (2). Severity and progression of liver fibrosis are difficult to assess, with liver biopsy currently remaining the most reliable clinical method. The qualitative evaluation of hepatic fibrosis by biopsies is limited by interobserver variability. Biopsies are clearly inadequate for the early clinical phase of drug development, where there is an imperative to-employ less invasive methods that identify effective compounds within a commercially acceptable time frame, usually measured in weeks to a maximum of three months of experimental therapeutic exposure. Further disadvantages are the low diagnostic specificity and the risk of bleeding. Therefore there is a need for surrogate markers of liver fibrosis. Serum tests allow a non-invasive assessment of fibrogenesis and fibrolysis in the liver and can be done repeatedly and at short time intervals (3). Serum tests measuring the dynamic processes of extracellular matrix synthesis (fibrogenesis) and extracellular matrix degradation (fibrolysis) reflect the amount of extracellular matrix present, the degree of fibrosis or the ongoing process of architectural change of the liver (4). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biopsy apparatus Inventor(s): Butcher, Charles; (Carmel, IN), Hancock, John P.; (Fishers, IN), Mark, Joseph L.; (Indianapolis, IN), Miller, Michael E.; (Trafalgar, IN) Correspondence: Rader, Fishman & Grauer Pllc; 39533 Woodward Avenue; Suite 140; Bloomfield Hills; MI; 48304-0610; US Patent Application Number: 20040049128 Date filed: August 12, 2003 Abstract: A disposable tissue removal device comprises a "tube within a tube" cutting element mounted to a handpiece. The inner cannula of the cutting element defines an inner lumen and terminates in an inwardly beveled, razor-sharp cutting edge. The inner cannula is driven by both a rotary motor and a reciprocating motor. At the end of its stroke, the inner cannula makes contact with the cutting board to completely sever the tissue. An aspiration vacuum is applied to the inner lumen to aspirate excised tissue through the inner cannula and into a collection trap that is removably mounted to the handpiece. The rotary and reciprocating motors are hydraulically powered through a foot pedal operated hydraulic circuit. The entire biopsy device is configured to be disposable. In one embodiment, the cutting element includes a cannula hub that can be connected to a fluid source, such as a valve-controlled saline bag. Excerpt(s): The present application is a continuation-in-part of U.S. application Ser. No. 09/707,022 filed on Nov. 6, 2000 in the name of inventor Michael E. Miller and assigned to the assignee of the present application. This invention relates to biopsy instruments and methods for taking a biopsy. More specifically, this invention relates to disposable biopsy devices for removing several tissue samples using a single insertion. In the diagnosis and treatment of breast cancer, it is often necessary to remove multiple tissue samples from a suspicious mass. The suspicious mass is typically discovered during a preliminary examination involving visual examination, palpitation, X-ray, MRI, ultrasound imaging or other detection means. When this preliminary examination reveals a suspicious mass, the mass must be evaluated by taking a biopsy in order to determine whether the mass is malignant or benign. Early diagnosis of breast cancer, as
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well as other forms of cancer, can prevent the spread of cancerous cells to other parts of the body and ultimately prevent fatal results. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biopsy device Inventor(s): Sayet, Peter H.; (Fort Lauderdale, FL), Sutherland, Lloyd A.; (Boca Raton, FL), Wolfe, Michael; (Newton, MA) Correspondence: Gregory A. Nelson, ESQ.; Akerman, Senterfitt & Eidson, P.A.; 222 Lakeview Avenue, Suite 400; P.O. Box 3188; West Palm Beach; FL; 33402-3188; US Patent Application Number: 20040006284 Date filed: July 2, 2002 Abstract: A biopsy device includes a housing and at least one biopsy mechanism moveably connected to the housing. The biopsy can be provided on a biopsy arm. An actuator moves the biopsy arm and operates the biopsy mechanism. The biopsy arms with the biopsy mechanisms are preferably removable from the housing, such that the housing can be used again for subsequent biopsy procedures. Excerpt(s): This invention relates generally to medical instrumentation, and more particularly to biopsy devices. Biopsy devices are used to obtain tissue samples, usually for purposes of performing testing on these samples. In order to obtain a biopsy sample, the biopsy device must be inserted into the body to reach the tissue for which the biopsy is to be taken. The device must be positioned next to the tissue, the sample taken, and the device removed. Some biopsy protocols require multiple samples to be taken. In the case of a body canal, samples from different positions on the circumference of the canal are sometimes required for each axial position along the canal length. This can require multiple devices if sterility and sample integrity are to be maintained, or multiple procedures if more than one biopsy site is required to be sampled. It is difficult to maintain the stability and position of a biopsy device upon insertion into the body. Biopsy procedures usually involve small incisions such that manipulation of the device at the point of the biopsy is not directly possible. It is possible for the biopsy sample to become dislodged from the biopsy device during removal of the device from the body. Secure retention of the sample is necessary to avoid repeating the process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Biopsy device handle assembly Inventor(s): Groenke, Gregory C.; (Gurnee, IL), Krueger, John; (Milwaukee, WI) Correspondence: Kimberly Diliberti, Paralegal; Allegiance Corporation; 1430 Waukegan Road; Mcgaw Park; IL; 60085; US Patent Application Number: 20040077973 Date filed: October 22, 2002 Abstract: The invention described herein relates to a handle assembly for biopsy devices, such as bone biopsy core sampling devices and bone marrow aspiration devices, which comprise an outer cannula and stylet component structure. The handle assembly permits securing and removal of the inner stylet from the inside of the outer cannula by virtue of separating top and bottom portions of the handle, and at the same
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time enhances the comfort and maneuverability of the entire device during its use. In particular, the invention provides a biopsy device comprising a handle assembly, said handle assembly comprising at least two separable handle components together forming a generally elongated arcuate handle. The assembled handle comprises a generally elongate arcuate handle wherein the outward curve is at the top portion and the inward curve is at the bottom portion. The handle assembly comprises four concave arcuate indentations located on the side of the handle and defining corresponding arcuate regions of the outer perimeter of the top portion upper and lower surfaces and the bottom portion upper and lower surfaces. The exterior surface of the handle assembly is smooth and rounded for ergonomic comfort. Excerpt(s): The invention relates to biopsy devices useful during medical procedures. In particular, the invention pertains to a handle assembly for use in conjunction with bone biopsy devices. Biopsy devices which can be used to obtain tissue samples from harder tissues, such as bone, are well known in the art. Bone biopsy devices can contain a structure which can penetrate through the cortex of bone and obtain a "core" sample of the harder bone tissue and softer marrow tissue within from the sampling site. One common structure which is present on certain bone biopsy devices is a cannula and inner stylet or trocar assembly. In these devices, the stylet or trocar is initially secured within an outer cannula and has a sharpened tip which is used to bore into the bone to access the sampling site. Another variety of biopsy devices involve those which use aspiration to obtain liquid samples from a tissue site, such as contents found in bone marrow. A variety of devices having the stylet-and-cannula structure have been developed. Furthermore, a variety of approaches have also been developed in an attempt to make the use of such devices more accurate and comfortable for the practitioner. The comfort and ergonomics of such devices is especially important given the pressure and forces, both rotationally as well as longitudinally, which is applied by the user to the device during the penetration and sampling steps. Various biopsy device handle configurations are described by Ausherman et al. U.S. Pat. No. 4,793,363, Mehl U.S. Pat. No. 4,469,109, Tretinyak U.S. Pat. No. 4,630,616, Mathis et al. U.S. Pat. No. 6,221,029, Fleming, III et al. U.S. Pat. No. 6,302,852, Fleming, III U.S. Pat. No. 6,312,394, and Lee U.S. Pat. No. 4,655,226. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biopsy devices and methods Inventor(s): Selis, James E.; (Birmingham, MI) Correspondence: Dobrusin & Thennisch PC; 401 S Old Woodward Ave; Suite 311; Birmingham; MI; 48009; US Patent Application Number: 20040097981 Date filed: July 31, 2003 Abstract: An improved system for mammography analysis and methods of using the same. In one aspect, a clip comprises a first portion and at least one additional second portion connected to the first portion, the first and second portions adapted for elastic deformation for engaging tissue. In anther aspect, an improved actuator for performing a breast biopsy is used to deploy a clip. In yet another aspect of the invention, there is contemplated a system for marking an evacuated breast cyst. Excerpt(s): The present application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/400,113 (filed Aug. 1, 2002), the contents of which
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are hereby incorporated by reference in their entirety. The present invention relates to devices and methods for performing biopsies, and more particularly to breast implantation clips for use as markers in mammography. Percutaneous biopsy of the breast is a well-accepted alternative to open surgical biopsy with needle localization for those lesions seen by mammography or ultrasound but not able to be felt by the surgeon. When percutaneous biopsy is performed, it is frequently necessary to place a metal clip at the site of biopsy. This is done for several reasons. For example, the lesion biopsied might be partially or entirely removed. If the lesion is proven to be malignant, it is necessary to subsequently do a wide excisional biopsy after needle localization to remove any residual malignancy. The clip makes the site of biopsy apparent, assuring accurate localization. In addition, if something is seen on both mammography and ultrasound, it is not always certain that the lesions are one and the same. A biopsy under ultrasound guidance with placement of a clip allows confirmation by mammography that the lesion is the same or different than the one seen on the mammogram. Further, the presence of a clip seen on a mammogram alerts the radiologist that a biopsy has been performed, prompting the radiologist to more closely evaluate the site of biopsy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biopsy marker delivery system Inventor(s): Kim, Steven; (Los Altos, CA), Zarins, Sascha; (San Jose, CA) Correspondence: Morrison & Foerster Llp; 425 Market Street; San Francisco; CA; 941052482; US Patent Application Number: 20040049126 Date filed: August 11, 2003 Abstract: An apparatus for delivering subcutaneous cavity marking devices. More particularly, the delivery devices may be used with biopsy systems permitting efficient placement of a biopsy marker within a cavity. The device may include an intermediate member which assists in deployment of the marking device. The devices may also include a deployment lock to prevent premature deployment of a biopsy marker. The invention may further include the capability to match an orientation of a biopsy probe which has been rotated upon procurement of a biopsy sample. Excerpt(s): This invention is directed to delivery devices for delivering subcutaneous cavity marking devices. More particularly, the delivery device may be used with biopsy systems permitting efficient placement of a biopsy marker within a cavity. The device may include an intermediate member which assists in deployment of the marking device. The device may also include a deployment lock to prevent premature deployment of a biopsy marker. The invention may further include the capability to match an orientation of a biopsy probe that has been rotated upon procurement of a biopsy sample. Over 1.1 million breast biopsies are performed each year in the United States alone. Of these, about 80% of the lesions excised during biopsy are found to be benign while about 20% of these lesions are malignant. In the field of breast cancer, stereotactically guided and percutaneous biopsy procedures have increased in frequency as well as in accuracy as modern imaging techniques allow the physician to locate lesions with ever-increasing precision. However, for any given biopsy procedure, a subsequent examination of the biopsy site is very often desirable. There is an important need to determine the location, most notably the center, as well as the orientation and periphery of the subcutaneous cavity from which the lesion is removed.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biopsy needle Inventor(s): Angel, Luis F.; ( San Antonio, TX) Correspondence: Eric B. Meyertons; Meyertons, Hood, Kivlin, Kowert & Goetzel, P.C.; P.O. Box 398; Austin; TX; 78767-0398; US Patent Application Number: 20040019297 Date filed: March 20, 2003 Abstract: A biopsy needle assembly may include a sample needle, an actuator and a cutter. A sample needle may include a sample opening. A tissue sample may be positioned in the sample opening when the sample needle is inserted into tissue of a patient. The actuator may be activated to move the cutter relative to the sample needle and separate sample tissue in the sample opening from adjacent tissue. The biopsy needle assembly may be removed from the patient and the sample may be removed from the sample opening. In some embodiments, the sample needle may be inserted in tissue through an instrument (e.g., an endoscope). The biopsy needle assembly may include a sheath that inhibits a sample needle and a cutter from contacting the instrument when the biopsy needle is inserted in the instrument. Excerpt(s): This application claims priority to Provisional Patent Application No. 60/365,989 entitled "BIOPSY NEEDLE" filed on Mar. 20, 2002. The present invention generally relates to a biopsy needle for obtaining tissue samples. Embodiments of the invention relate to a biopsy needle for obtaining samples from within a patient through an endoscope or other instrument. A biopsy procedure may be performed to determine if suspect cells are diseased or cancerous. The biopsy procedure may involve obtaining a tissue sample and/or body fluids from a patient. Tests performed on the tissue sample and/or body fluids may provide information for diagnosis of the patient's condition. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Biopsy site marker and process and apparatus for applying it Inventor(s): Burbank, Fred H.; (San Juan Capistrano, CA), Forcier, Nancy; (Laguna Niguel, CA), Jones, Michael L.; (Capistrano Beach, CA), Lubock, Paul; (Laguna Niguel, CA) Correspondence: Edward J. Lynch; Duane Morris Llp; Spear Tower, Suite 2000; One Market; San Francisco; CA; 94105; US Patent Application Number: 20040101479 Date filed: October 10, 2003 Abstract: A biopsy site marker comprises small bodies or pellets of gelatin which enclose substantially in their interior a radio (X-ray) opaque object. The gelatin pellets are deposited into the biopsy site, typically a cylindrical opening in the tissue created by the recent use of a vacuum assisted large core biopsy device, by an applicator device that includes an elongated cylindrical body that forms a flexible tube and a piston slidable in the tube. One end of the tube is placed into the biopsy site. Typically, several gelatin pellets, only some of which typically do, but all of which may contain the radio
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opaque object, are deposited sequentially into the site through the tube. The radio opaque objects contained in the gelatin bodies are of a non-biological configuration and readily identifiable as man-made object, so that in observation by typical mammography equipment they do not assume the shape of a line, whereby they are readily distinguishable from granules and lines of calcification. Excerpt(s): The present invention is in the field of markers to be employed at biopsy sites to permanently mark the site, and to methods and apparatus for applying the permanent marker. More particularly, the present invention relates to a marker that is optimally adapted for marking biopsy sites in human breast tissue with permanently placed markers that are detectable by X-ray. In modern medical practice small tissue samples, known as biopsy specimens, are often removed from tumors, lesions, organs, muscles and other tissues of the body. The removal of tissue samples may be accomplished by open surgical technique, or through the use of a specialized biopsy instruments such as a biopsy needle. A well known state-of-the-art instrument that is often used in connection with the practice of the present invention is known as the "vacuum assisted large core biopsy device". After a tissue sample has been removed, it is typically subjected to diagnostic tests or examinations to determine cytology, histology, presence or absence of chemical substances that act as indicators for disease states, or the presence of bacteria or other microbes. The above mentioned and other diagnostic tests and examinations per se are well known in the art and need not be described here. It is sufficient to note that the information obtained from these diagnostic tests and/or examinations is often of vital importance for the well-being of the patient and is used to make or confirm diagnoses and often to formulate treatment plans for the patient. As is known, obtaining a tissue sample by biopsy and the subsequent examination are frequently, almost invariably, employed in the diagnosis of cancers and other malignant tumors, or to confirm that a suspected lesion or tumor is not malignant, and are frequently used to devise a plan for the appropriate surgical procedure or other course of treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Calibration method for an automated surgical biopsy device Inventor(s): Burdorff, Mark A.; (Loveland, OH), Dlugos, Daniel F.; (West Chester, OH), Gleason, Scott A.; (Oshkosh, WI), Hibner, John A.; (Mason, OH), Schmidt, Brian W.; (Neenah, WI) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040054299 Date filed: May 2, 2003 Abstract: A method is provided for calibrating a surgical biopsy system. The biopsy system includes a biopsy instrument and control unit. The biopsy instrument includes a piercer, rotatable cutter, and a port for receiving tissue samples. The method comprises the steps of translating the cutter distally until the translation of the cutter is stopped at an extended position and recording the extended position. The cutter is then translated from the extended position proximally until the translation of the cutter is stopped at a retracted position proximal to the extended position. The retracted position is recorded. The method further comprises the step of rotating the cutter to a rotation speed while the cutter is located at the retracted position and, if determined that the rotation speed is
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within a predetermined rotation speed range, a feedback signal is provided on the display allowing the operator to progress to the next procedural step. Excerpt(s): This application is related to the following co-pending U.S. patent application: Ser. No. 08/825,899 filed on Apr. 2, 1997. This application is further related to the following co-pending U.S. patent applications, which are hereby incorporated herein by reference: Ser. No. 09/543,122 filed on Oct. 23, 1998; Ser. No. 09/466,391 filed Dec. 17, 1999; Ser. No. 09/466,491 filed Dec. 17, 1999. The present invention relates, in general, to a method of calibrating a biopsy system and, more particularly, to a method of calibrating the translation and rotation of a cutter in a biopsy instrument. The method may further be used to determine the correct selection of probe size for the software installed in the control unit. The diagnosis and treatment of patients with cancerous tumors, pre-malignant conditions, and other disorders has long been an area of intense investigation. Non-invasive methods for examining tissue include palpation, X-ray, magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound imaging. When a physician suspects that tissue may contain cancerous cells, a biopsy may be done using either an open procedure or a percutaneous procedure. For an open procedure, a scalpel is used to create a large incision in the tissue to provide direct viewing and access to the tissue mass of interest. The entire mass (excisional biopsy) or a part of the mass (incisional biopsy) may then be removed. In most percutaneous biopsy procedures, a needle-like instrument is inserted through a very small incision to access the tissue mass of interest and obtain a tissue sample for later examination and analysis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cloning and characterization of a novel BK channel isoform highly expressed in glioma cells Inventor(s): Liu, Xiaojin; (Boston, MA), Sontheimer, Harald W.; (US) Correspondence: Bradley Arant Rose & White, Llp; Intellectual Property DepartmentNwj; 1819 Fifth Avenue North; Birmingham; AL; 35203-2104; US Patent Application Number: 20040081973 Date filed: February 27, 2003 Abstract: Described is the cloning and functional characterization of a novel splice variant of hSlo, the gene encoding the.alpha.-subunit of IbTX sensitive human BK channels. The novel isoform of BK channels, which was termed gBK, contains a 63 amino acid insert at splice site 2, which differs by 33 amino acids from its nearest relative hbr5. gBK channels were over-expressed in glioma cells as evident from examination of human biopsy specimens. Moreover, gBK channel expression correlated positively with the relative degrees of malignancy of the tumor tissues. Heterologous expression of gBK in oocytes revealed that the pharmacological and biophysical properties of gBK are consistent with the properties of native BK currents in glioma cells. Furthermore, even when compared with its most homologous form hbr5, gBK showed distinct properties, including slowed channel activation and importantly, enhanced Ca.sup.2+ sensitivity at physiologically relevant [Ca.sup.2+].sub.i values. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/360,384, filed Feb. 28, 2003. The present disclosure relates generally to K.sup.+ channels. Specifically, the present disclosure relates to the identification and characterization of a novel BK channel from human glial tissue. There are a variety of K.sup.+ channels subtypes involved in human physiology. These K.sup.+ channels
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regulate a myriad of processes, ranging from regulation of the heartbeat to control of the excitability of nerve cells. Several classes of K.sup.+ channels have been described based on their pharmacological properties and electrophysiological properties, and include the voltage gated K.sup.+ channels, the ATP-regulated K.sup.+ channels, Ca.sup.+-activated K.sup.+ channels, Na.sup.+-activated K.sup.+ channels, and K.sup.+ channels activated in response to specific compounds. An important member of the K.sup.+ channel family includes the voltage-dependent large-conductance Ca.sup.2+-activated K.sup.+ channels (BK channels). Intracellular calcium concentration [Ca.sup.2+]i and membrane potential regulate the BK channels. As an example, BK channels are opened to allow K.sup.+ efflux in response to an increase in intracellular Ca.sup.2+ concentration. Therefore, modulation of BK channel activity impacts various pathways that depend on an influx of calcium through voltage dependent pathways. The BK channels are widely expressed in excitable and nonexcitable cells. BK channels can be composed of either an.alpha.-subunit homodimer, or a heterodimer comprising an.alpha.-subunit and a.beta.-subunit. BK channels from most mammalian neurons are not thought to be associated with a.beta.-subunit. BK channels exhibit diverse electrophysiological properties, which are in part due to alternative splicing of their.alpha.-subunits. Regulation by the.beta.-subunit may also play a role in BK channel function. BK channels, resemble a unique class of ion channels that couple intracellular chemical signaling to electric signaling (McManus, 1991). BK currents have been implicated in growth control of glial cells and BK channels with novel biophysical properties have been characterized in human glioma cells. BK channels have been indicated to regulate neuronal firing (MacDermott and Weight, 1982; Robitaille and Charlton, 1992; Robitaille et al., 1993; Poolos and Johnston, 1999; Golding et al., 1999), endocrine cell secretion (Marty, 1989; Lingle et al., 1996), and smooth muscle tone (Nelson and Quayle, 1995; Brenner et al., 2000). In nonexcitable cells, such as epithelial, endothelial, or glial cells, BK channels may contribute to diverse biological functions ranging from osmoregulation (Turnheim et al., 1989), cell proliferation (Wiecha et al., 1998), to cell migration (Soroceanu et al., 1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Computer aided treatment planning Inventor(s): Chen, Dongqing; (Port Jefferson Station, NY), Kaufman, Arie E; (Plainview, NY), Kreeger, Kevin; (East Stauket, NY), Li, Bin; (Centereach, NY), Liang, Zhengrong; (Stony Brook, NY), Roque, Clemente T; (Stony Brook, NY), Smouha, Eric E; (Northport, NY), Wax, Mark R; (Greenlawn, NY) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20040015070 Date filed: February 19, 2003 Abstract: A method of computer aided treatment planning is performed by generating and manipulating a three dimensional (3D) image of a region which includes at least one anatomical structure for which treatment, such as surgery, biopsy, tissue component analysis, prosthesis implantation, radiation, chemotherapy and the like, is contemplated. A virtual intervention, which simulates at least a portion of the contemplated treatment, is performed in the 3D image. The user can then determine the effect of the intervention and interactively modify the intervention for improved treatment results. Preferably, a warning is automatically provided if the intervention posses a risk of detrimental effect. The user can navigate through the contemplated
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region in the 3D image and assess the results. The treatment plans can be saved for comparison and post treatment evaluation. Excerpt(s): The present invention relates generally to surgical planning and more particularly relates to a system and method of using three dimensional interactive computer visualization in surgical planning, optimization and evaluation. In many areas of medical treatment, it would be beneficial for a medical practitioner to be able to visualize a region for which treatment is contemplated and to accurately simulate the contemplated treatment. By visualizing the effect of the simulated treatment and altering the proposed treatment to optimize the results in a virtual setting, results can be improved and risks associated with the actual treatment can be reduced. This is particularly true in the case of invasive procedures such as surgery, biopsies and prosthesis implantation. The virtual setting would serve both as a tool for the guidance for actual treatment and as a "gold standard" for evaluation of the actual treatment and for follow up management. The ear is a specialized organ for which the computer aided treatment planning is expected to play a valuable role. The ear is an internal organ that is difficult to examine because it is encased in the temporal bone. The ear also contains important anatomic structures, including the hearing bones (ossicles), inner ear organs of hearing and balance, and facial nerve. Congenital aural atresia (CAA) is a congenital developmental anomaly of the middle ear that manifests with varying degrees of external auditory canal stenosis or atresia, ossicular derangements, poorly developed mastoid and tympanic cavities. This disease results in conductive hearing loss which can be severe. In some cases, however, CAA can be treated surgically. However, because of the complex anatomy of the ear and the risks associated with this surgical procedure, such as facial paralysis, thorough surgical planning is required to assess and maximize the likelihood of successful surgery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
DIAGNOSTIC NEEDLE ARTHROSCOPY AND LAVAGE SYSTEM Inventor(s): Kadan, Jeffrey S.; (Redondo Beach, CA) Correspondence: David O'reilly; Suite 200; 1800 Bridgegate Street; Westlake Village; CA; 91361; US Patent Application Number: 20040082915 Date filed: February 21, 2003 Abstract: A system for performing diagnostic needle arthroscopy and lavage through a single port of entry into the joint compartment. The system is comprised of a handpiece having valves for irrigation and suctioning, a diagnostic cannula attached to the handpiece. The system includes a mobile cart, camera, a high-resolution monitor and an air compressor to power individually controlled irrigation pumps to deliver irrigation fluid to a handpiece and a vacuum suction console to collect fluid. The system also includes a biopsy cannula that can be exchanged for the diagnostic cannula using an exchange rod. The biopsy cannula is comprised of a pair of piggyback cannulas, one for visualization, diagnosis, irrigation and suction while the other is for insertion of a biopsy instrument or surgical devices. The biopsy instrument is comprised of a thin shaft connected to forceps at a distal end for performing surgical procedures. Excerpt(s): This application is a Continuation-In-Part of Application Ser. No. 10/165,691 filed Jun. 7, 2002 and a Continuation of application Ser. No. 09/570,324, filed May 12, 2000, and application Ser. No. 09/495,601 filed Feb. 1, 2000. This invention relates to
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systems to perform arthroscopies of joints such as the knee and more particularly relates to a diagnostic needle arthroscopy and lavage, (DNAL) system for performing arthroscopies through a single port. Arthroscopy is a surgical procedure in which an endoscope (arthroscope) is inserted into a joint. Fluid is then injected into the joint to slightly distend the joint and allow visualization of structures within the joint. Surgery is usually viewed on a monitor so that the whole operating team can visualize the surgical procedure that is being performed. The arthroscopy procedure falls into two types; operative and diagnostic. Operative arthroscopy is more interventional, utilizing larger devices and multiple ports to accomplish a variety of procedures designed to repair internal derangement or tears of intra-articular structures. Diagnostic arthroscopy is less invasive, requiring smaller devices and a single port of entry into the joint. Operative arthroscopes are typically four (4) mm in diameter. The operative arthroscopic procedure is often conducted under general anesthesia and is used to examine and treat the inside of the joint for damaged tissue. Most common types of surgery using operative arthroscopic procedures includes the removal or repair of torn meniscus (cartilage), ligament reconstruction, removal of loose debris and trimming or shaving damaged cartilage. Diagnostic arthroscopy is done under local anesthetic only and is most often accompanied by a thorough rinsing out of the joint (lavage). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Dual action aspiration biopsy needle Inventor(s): Fisher, John S.; (Belleair, FL) Correspondence: Smith & Hopen PA; 15950 Bay Vista Drive; Suite 220; Clearwater; FL; 33760 Patent Application Number: 20030236471 Date filed: September 23, 2002 Abstract: A dual action biopsy needle scrapes tissue of cellular thickness from a lesion during forward and rearward reciprocations of the needle along its longitudinal axis of symmetry. A first sharp edge, formed by a beveled distal end of the needle, scrapes tissue during proximal-to-distal travel of the needle. A second sharp edge is provided by a transversely disposed slot formed in the needle near the first sharp edge. The second sharp edge scrapes tissue during distal-to-proximal travel of the needle. In a first embodiment, the second sharp edge is coincident with an exterior surface of the needle. In a second embodiment, the second sharp edge is elevated with respect to the exterior surface and in a third embodiment the second sharp edge is recessed. Additional embodiments include a second slot, a channel, and a hinge for enabling pivotal movement of the second and third sharp edges. Excerpt(s): This disclosure is a continuation-in-part of a disclosure of the same title and same inventor, bearing application Ser. No. 09/682,252, filed Aug. 9, 2001. This invention relates, generally, to aspiration biopsy needles. More particularly, it relates to an aspiration biopsy needle having an enhanced cellular material collection capability. There are three main types of biopsy procedures. In a first type, a conventional surgical incision is made and the patient's body is opened so that a surgeon may retrieve one or more large pieces of the tumor or lesion to be tested for malignancy. This type of biopsy is very invasive, expensive to perform, and requires a considerable recovery time. Inventive endeavors in the field have resulted in two improved procedures that substantially reduce the invasiveness of the biopsy procedure, as well as the expense of the procedure and the length of the recovery time.
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Endoscope sheath assemblies having an attached biopsy sampling device Inventor(s): Martone, Stephen; (Westford, MA), Oneda, Katsumi; (Alpine, NJ) Correspondence: Dorsey & Whitney Llp; Intellectual Property Department; Suite 3400; 1420 Fifth Avenue; Seattle; WA; 98101; US Patent Application Number: 20040059253 Date filed: January 4, 2002 Abstract: Apparatus and methods for obtaining biopsy samples using an endoscope assembly are disclosed. In one embodiment, an assembly adapted for use with an endoscopic insertion tube includes a sheath having a body portion adapted to at least partially encapsulate a distal portion of the insertion tube, and a biopsy sampling device attached to the sheath and including a collection member proximate an end of the body portion. The biopsy sampling device may be attached to the body portion of the sheath, or alternately, may be attached to an enclosed distal end of the sheath. The assembly may also include a cover attached to the sheath and positionable proximate the biopsy sampling device. An actuation member may be attached to the cover and may extend along the sheath, allowing the operator to actuate the cover between a covered position and a collecting position. Excerpt(s): The present invention is directed toward apparatus and methods for obtaining biopsy samples using an endoscope, and more specifically, to endoscope sheath assemblies having an attached biopsy sampling device. Endoscopes are widely used for a variety of medical procedures. To improve their performance, endoscopes have been optimized in various ways to best accomplish their purpose. Examples of specialized endoscopes include angioscopes, colonoscopes, bronchoscopes, and arthroscopes. During a medical procedure, a surgical instrument 50 having a biopsy sampling device 52 is inserted into the proximal end 48 of the channel 46, and slid through the channel 46 until the biopsy sampling device 52 emerges at the working end 26. A variety of biopsy sampling devices 52 are known, including forceps (e.g. U.S. Pat. No. 5,820,630 issued to Lind), loop and cup devices (e.g. U.S. Pat. No. 5,417,697 issued to Wilk et al., U.S. Pat. No. 5,741,271 issued to Nakao et al.), and cylindrical cutting devices (e.g. U.S. Pat. No. 4,651,753 issued to Lifton). In alternate embodiments, the biopsy sampling device 52 may be inserted through one or more channels that are integrated into the insertion tube 22 of the endoscope 20, as described, for example, in the abovereferenced patents to Silverstein and Nakao et al. After a biopsy sample is obtained, the biopsy sampling device 52 containing the biopsy sample may be withdrawn through the channel 46, or alternately, the entire insertion tube 22 may be withdrawn from the patient's body with the biopsy sampling device 52 remaining in position near the working end 26. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Fluid pressure-actuated medical device Inventor(s): Ward, Tim E.; (Bedford, NH) Correspondence: Testa, Hurwitz & Thibeault, Llp; High Street Tower; 125 High Street; Boston; MA; 02110; US Patent Application Number: 20040064067 Date filed: October 1, 2002 Abstract: An apparatus and method are described for actuating a minimally invasive medical device using fluid pressure. The invention involves a medical device that includes a fluid source, such as a compressible bladder that may apply positive fluid pressure into a sheath to controllably deploy an end-effector from a distal end of the sheath. In some embodiments, the fluid source may apply negative fluid pressure into the sheath to controllably retract the end-effector into the distal end of the sheath. Typical end-effectors for use with the medical device of the invention include biopsy devices and retrieval devices, including basket-type retrieval devices and grasper retrieval devices. Generally, the fluid that is used to actuate the device may be a liquid or a gas, including air. Excerpt(s): The invention generally relates to a minimally invasive medical device for use in procedures such as retrieval or biopsy. More particularly, the invention relates to a minimally invasive medical device that is actuated through application of fluid or air pressure. Current minimally invasive medical devices for use in operations such as retrieval or biopsy are typically operated by mechanical means, using a pull wire. Typically, a distal end of the pull wire connects to an end-effector, such as a basket-type retrieval device, a grasper, a biopsy device, etc. Generally, the proximal end of the pull wire is connected to a control or actuation mechanism in the handle of the medical device. The pull wire typically transmits movement in a control or actuation mechanism in the handle of the device to the end-effector. Through use of such a pull wire, or a series of pull wires, the end-effector can be controlled to extend from the end of a sheath, retract into the sheath, cut away a sample for a biopsy, or to take other actions that are typically performed by devices such as graspers, basket-type retrieval devices or biopsy devices. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Genotyping by in situ PCR amplification of a polynucleotide in a tissue biopsy Inventor(s): Kwon, Jai W.; (South Pasadena, CA) Correspondence: Park & Sutton Llp; 3255 Wilshire Blvd; Suite 1110; Los Angeles; CA; 90010; US Patent Application Number: 20040038213 Date filed: August 6, 2002 Abstract: Reagents and method for genotyping mice and other animals by in situ Polymerase Chain Reaction amplification of a target polynucleotide in the tissue biopsy. The reagent is comprised of non-ionic detergents, a protease, a buffering agent, a metal ion cofactor, a chelating agent and a salt. The method is comprised of taking a tissue biopsy; admixing it with the reagent; a Lysing Cycle, an inactivation cycle, an amplification step and a detection step.
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Excerpt(s): This invention pertains generally to the art of releasing polynucleotides from cells and more particularly to genotyping through in situ Polymerase Chain Reaction amplification of a target gene allele in a tissue biopsy. Genetically altered mice have been used to study gene function and human disease. Over the past decade, thousands of new mouse strains have been developed which will eventually cover all of the genes in a mouse. Genetically altered mice have provided researchers and the medical community with an immense new resource of biological tools and information. Morris Alpert called the development of knock out mice the most significant advance in research of the twentieth century. A research study typically involves lots of 500 genetically altered mice and each mouse needs to be genotyped. In genotyping, a tail biopsy is commonly used as a source of chromosomes (DNA). To facilitate detecting a gene allele in the biopsy, it is common practice to amplify a portion of the chromosome containing the gene allele using Polymerase Chain Reaction amplification (see, R. K. Saiki et al., "Primer-directed Enzymatic Amplification of DNA With A Thermostable DNA Polymerase," Science, pp. 487-491 (1988) (incorporated by reference).) The amplified fragment is then detected by methods such as hybridization to a polynucleotide array on a slide, a dot blot, a Southern blot, and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunogenic compositions to the CCK-B/gastrin receptor and methods for the treatment of tumors Inventor(s): Caplin, Martyn; (London, GB), Grimes, Stephen; (Davis, CA), Michaeli, Dov; (Larkspur, CA), Watson, Susan A.; (Edwalton, GB) Correspondence: White & Case Llp; Patent Department; 1155 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20040001842 Date filed: December 19, 2002 Abstract: The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a gastrin receptor immunomimic peptide conjugated to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the gastrinreceptor (GR) in gastrin responsive malignant or premalignant tumor, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The invention also comprises specific antibodies against the gastrin-receptor for passive immunization. Furthermore, the invention comprises cytotoxic molecule derivatized anti-GR antibodies. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention. Active and passive immunization can be combined providing an immune response against GR, G17 and/or G17-Gly. Excerpt(s): This application is a continuation in-part of Ser. No. 09/076,372, which claims the benefit under 35 U.S.C.sctn. 119(e), of U.S. Provisional Application No. 60/046,201 filed on May 12, 1997. Gastrin is a peptide hormone which occurs in two forms, tetratriacontagastrin (G34) and heptadecagastrin (G17), and is synthesized and secreted by specialized cells, G cells, that are located in the stomach antrum. The hormone is secreted into the circulating blood and binds to specific cells in the stomach, namely, enterochromaffin-like (ECL) and parietal cells, that indirectly or directly affect stomach acid output. Historically, gastrin hormones have been associated with the stimulation of gastric acid secretion (Edkins, J. S. 1905). (The full citations for the
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references cited herein are provided in the Reference section preceding the claims.) In recent years, evidence has accumulated that gastrin may act as a trophic factor within the gastrointestinal tract (Johnson, L. 1997) and that it can promote the growth of gastrointestinal cancers (Watson et al. 1989, Dickinson, C. J. 1995), as well as nongastrointestinal cancers including small cell carcinoma of the lung (Rehfeld et al. 1989). In the post-translational processing of gastrin, it is the "mature" carboxy-amidated form that binds to a cholecystokinin B/gastrin receptor with high affinity via its five carboxyterminal amino acids (Kopin et al. 1992). The CCK-B/gastrin receptor (GR) is a transmembrane protein which is coupled via a G protein to intracellular signal transduction pathways that in turn control the expression of various genes. The CCK-B/gastrin receptor belongs to a family of G protein-coupled receptors with seven transmembrane domains with equal affinity for both CCK and gastrin (Soll et al. 1984). This receptor was named a CCK type-B receptor because it was found predominantly in the brain (Wank et al. 1992). The receptor was subsequently found to be identical to the peripheral CCK/gastrin receptor (GR) in the parietal and ECL cells of the stomach (Nakata et al. 1992). This receptor has been well characterized in a number of normal (Fourmy et al. 1984, Grider et al. 1990) and tumor tissues (Singh et al. 1990, Watson et al. 1993), and extensively studied using the rat pancreatic adenocarcinoma cell line AR42J (Scemama et al. 1987). The AR42J GR cDNA has been cloned and sequenced, and it is more than 90% homologous in DNA sequence to the GR in rat and human brain, and more than 84% homologous in sequence to the canine parietal cell GR cDNA (Wank, S. A. 1995), demonstrating a high sequence homology even between species. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunological test and diagnostic kit for prostate adenocarcinoma Inventor(s): Charrier, Jean-Philippe; (Ecully, FR) Correspondence: James C Lydon; Suite 100; 100 Daingerfield Road; Alexandria; VA; 22314; US Patent Application Number: 20040038321 Date filed: December 12, 2002 Abstract: This invention concerns a test method for the purposes of diagnosis, prognosis or therapeutic monitoring in male patients with adenocarcinoma of the prostate or benign prostatic hyperplasia, which does not require a biopsy of prostate tissue, and which exploits the combination of at least one tissue-specific marker and at least one marker for inflammation in order to arrive at a diagnosis.The invention also concerns a process using such a method, an immunological test to implement such a process, and a diagnostic kit.The invention is applied to the diagnosis of adenocarcinoma of the prostate and benign prostatic hyperplasia. Excerpt(s): This invention concerns a screening or diagnostic method for the detection of prostate cancer (i.e. adenocarcinoma of the prostate, usually abbreviated to PCa) and benign prostatic hyperplasia (abbreviated to BPH) in patients, a method which does not involve the taking of a biopsy. More generally, the invention concerns a test method for the purposes of diagnosis, prognosis or therapeutic monitoring of cancer in human patients. By diagnosis, it is meant that the marker reveals whether or not the patient is suffering from a certain disease. By prognosis, it is meant that the marker reveals the seriousness of the disease. The prognosis can guide the therapeutic strategy. Finally, by therapeutic monitoring, it is meant that the marker can be used to follow the efficacy of treatment. If the chosen treatment strategy is failing (as revealed by the marker), the
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patient can be offered an alternative. Prostate-specific antigen (PSA) is synthesized by epithelial cells of the human prostate gland, probably in the form of an inactive zymogen (Lundwall et al. FEBS LeH 1987) and is secreted in the seminal fluid in an active form (Lilja, J. Clin Invest 1985). The biological activity of PSA in seminal fluid consists of controlled proteolysis of the most abundant proteins secreted by the seminal vesicles (Lilja, J. Clin Invest 1985; Lilja et al. J. Clin Invest 1987; Mc Gee et al. Biol. Reprod. 1988). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Kit for obtaining an endoarterial biopsy sample Inventor(s): Mann, David Marshall; (San Diego, CA) Correspondence: David Mann; 4720 Everts ST; San Diego; CA; 92109; US Patent Application Number: 20040031721 Date filed: April 30, 2003 Abstract: A kit for obtaining an endoarterial biopsy sample from a patient comprising: (i) packaging material enclosing one or more kit components; (ii) wherein the kit components comprise one or more of the following: a) an endoarterial biopsy catheter; b) Percutaneous Access Needle; c) Short Introducer Sheath with Dilator & Guidewire; d) Floppy Guidewire; e) Endhole Catheter with inflation syringe; f) Stiff Guidewire; g) Flushing Syringes; h) Long Introducer Sheath with Dilator; i) Biopsy specimen removal tool; j) Biopsy Cassettes; k) Specimen Containers; l) Connective Tubing; m) Vacuum Gauges & Canisters; and, n) Vacuum pump. Excerpt(s): The present invention relates to a kit for obtaining an endoarterial biopsy sample from a patient comprising a package and a catheter for harvesting an endoarterial biopsy sample. Cardiovascular catheterization procedures often require a plurality of instruments and equipment to successfully complete the procedure. In view of the number and variety of procedures performed in a modern catheterization facility, there is a need for an improved method of supplying all necessary articles to perform any particular type of cardiovascular catheterization in an efficient and organized fashion. U.S. Pat. Nos. 5,406,959 and 5,287,857, both of which are herein incorporated by reference in their entirety, describe a new variety of catheters which can be used to obtain an endoarterial biopsy sample of one or more interior layers of a patient's selected artery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Localization mechanism for an MRI compatible biopsy device Inventor(s): C. Tinsley, John III; (Cincinnati, OH), Thompson, Eric W.; (Pleasant Plain, OH), Tsonton, Mark; (Loveland, OH) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040077972 Date filed: October 18, 2002 Abstract: A localization mechanism, or fixture, is used in conjunction with a breast coil for breast compression and for guiding a core biopsy instrument during prone
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stereotactic biopsy procedures in both open and closed Magnetic Resonance Imaging (MRI) machines. The localization fixture can include a breast compression plate and a biopsy probe support plate for supporting a biopsy probe for movement along multiple perpendicular axes. The position of both the breast compression plate and the biopsy probe support plate can be adjustable along an axis which is generally parallel to a probe needle. Excerpt(s): The present application cross references and incorporates by reference copending U.S. Ser. No. 10/171,330, "LOCALIZATION MECHANISM FOR AN MRI COMPATIBLE BIOPSY DEVICE" filed on Jun. 12, 2002, the disclosure of which is hereby incorporated by reference in their entirety. The present invention relates, in general to devices for tissue sampling and, more particularly, to a device for positioning a biopsy probe with respect to a magnetic resonance imaging (MRI) device. Generally there are two ways to percutaneously obtain a portion of tissue from within the body, by aspiration or by core sampling. Aspiration of the tissue through a fine needle requires the tissue to be fragmented into small enough pieces to be withdrawn in a fluid medium. The method is less intrusive than other known sampling techniques, but one can only examine cells in the liquid (cytology) and not the cells and structure (pathology). In core sampling, a core or fragment of tissue is obtained for histologic examination, genetic tests, which may be done via a frozen or paraffin section. The type of biopsy used depends mainly on various factors present in the patient, and no single procedure is ideal for all cases. However, core biopsies seem to be more widely used by physicians. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Magnetic navigation system for diagnosis, biopsy and drug delivery vehicles Inventor(s): Jin, Sungho; (San Diego, CA) Correspondence: Glen E. Books, ESQ.; Lowenstein Sandler, PC; 65 Livingston Avenue; Roseland; NJ; 07068; US Patent Application Number: 20040050394 Date filed: September 12, 2002 Abstract: This invention discloses such a convenient navigation system and navigatable capsules which are useful for remote-controlled imaging, biopsy and programmable drug release within the body of an animal. The components of the system comprise a capsule dimensioned and shaped to move within the body. An anisotropic magnetic component is mechanically coupled to the capsule to move or orient the body in relation to an applied magnetic field, and a magnetic field generating system external of the body generates a three dimensionally oriented magnetic field within the body to move or orient capsule. Excerpt(s): This invention relates to bioengineering systems, and in particular, to a magnetic navigation system for moving a device within the body of an animal such as a human being. The system is particularly useful within tracts, ducts or cavities such as the gastrointestinal (GI) tract. Various diagnostic techniques are used for detection of tumors, ulcers, and other abnormal conditions in the body. These techniques include xray imaging, ultrasonic testing, MRI, endoscopy, sigmoidoscopy and colonoscopy. Recently, a camera-in-a-capsule device has been developed and reported, see U.S. Pat. No. 5,604,531, "In vivo video camera system" issued to Iddan et al. on Feb. 18, 1997 and U.S. Pat. No. 6,428,469, "Energy management of a video capsule" issued to Iddan et al.
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on Aug. 6, 2002. Recent FDA approval (August, 2001) of an ingestible camera developed by Given Imaging Ltd. and tested at New York Mount Sinai Hospital received considerable news media attention. Such a device is schematically illustrated in FIGS. 1 and 2. Referring to FIGS. 1 and 2, the ingestible camera 10 is a finger-tip sized capsule 11 containing a camera composed of lens 12, an image detector 13 and one or more light sources 14. A wireless transmitter 15 (including antenna) is provided for video signal transmission. The capsule also includes, batteries 16, and circuit chips (not shown). When a patient swallows the capsule, the natural muscular waves of the digestive tract propel it downward; and, as it goes down, the camera takes pictures of the small intestine wall for video transmission to detect tumors, ulcers, or causes of bleeding. This procedure permits the diagnosis of the small intestine, which is difficult to access by colonoscopy. For larger regions, such as the stomach or the large intestine, this type of non-guided camera tends to lose orientation and reliable imaging covering all surface areas is no longer be possible. It would be desirable if the position of the camera could be controlled so that no portion of the GI tract surface would be missed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and apparatus for cross-modality comparisons and correlation Inventor(s): Weinberg, Irving N.; (Bethesda, MD) Correspondence: Patent Adminstrator; Katten Muchin Zavis Rosenman; 525 West Monroe Street; Suite 1600; Chicago; IL; 60661-3693; US Patent Application Number: 20040057609 Date filed: September 17, 2003 Abstract: A system and a method for determining a biopsy location in a body part are provided. The system includes a first device configured to obtain digital physiological image data about the body part, a second device configured to obtain anatomical image data about the body part, a monitor configured to display the anatomical image data, a signal processing module that includes an analog-to-digital converter configured to digitize the anatomical image data, a memory configured to store the digital physiological image data and the digitized anatomical image data, and a correlator coupled to the memory and configured to correlate the digital physiological image data with the digitized anatomical image data and to produce a combined image as a result of the correlation. A determination of a biopsy location is made on the basis of the combined image. The first device may include a positron emission tomography scanner machine. The second device may include one of the group consisting of a digital x-ray machine, an x-ray mammography machine, an x-ray cranial axial tomography machine, a magnetic resonance imaging machine, and an ultrasound machine. The system may also include a localization device, such as a computer mouse, that is configured to select a preferred subset of the second image data based on the digital physiological image data. The first device may be configured to use a predetermined spatial coordinate system. The correlator may include a transformer configured to transform the data into the predetermined spatial coordinate system. Excerpt(s): This application claims priority under 35 U.S.C. 119(e) to U.S. Provisional Application Serial No. 60/411,787, entitled "Method and Apparatus for Cross-Modality Comparisons and Correlation", filed Sep. 19, 2002, the contents of which are incorporated by reference herein. This application also claims priority under 35 U.S.C. 119(e) to U.S. Provisional Application Serial No. 60/425,288, entitled "Method and Apparatus for Comparing and Correlating PET and X-ray Images", filed Nov. 12, 2002,
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the contents of which are incorporated by reference herein. The present invention relates to a method and an apparatus for determining a biopsy location in a body part, and more particularly a method and an apparatus for correlating image data obtained from at least two separate devices to determine a biopsy location in a body part. Increasing the number of medical imaging studies that apply to a single feature or to several features can increase the diagnostic confidence of the physician interpreting the studies. Diagnostic confidence is increased further if the image sets are correlated; i.e., the spatial coordinate systems of the image sets are identical. For display purposes, once the spatial coordinate systems are shared, it is often helpful to display the images in a single window. In the past, such "correlative image displays" have been implemented by using gray-scale for one image set (i.e., x-ray) and a color scale for the second set. Alternatively, one image set uses hue and the other intensity. Aside from increasing diagnostic confidence, correlating images can be useful if each image set has a different intrinsic utility. For example, an imaging modality such as x-ray imaging has high spatial resolution and is therefore often better for guiding interventions, because the spatial resolution allows the user to avoid important anatomic structures of interest (e.g., major blood vessels). Another imaging modality (e.g., positron emission tomography, or "PET") is useful for providing biochemical and/or physiological information about structures in the human body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and apparatus for MR-guided biopsy Inventor(s): Daum, Wolfgang; (Groton, MA), Winkel, Axel; (Schwerin, DE) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20040092810 Date filed: February 14, 2003 Abstract: The subject invention pertains to a method and apparatus for MR-guided biopsy. The subject invention can be applied to, for example, prostate biopsy. In a specific embodiment, the subject invention can provide a mechanical tool for stabilizing the patient in prone position and to guide a biopsy needle into defined targeted lesions in the prostate gland. The patient can lay prone in the MRI. The subject apparatus can guide an MR-visible, sterile needle sleeve, which can have a hollow tube filled with contrast media, through the anus onto the inner wall of the colon. Due to the visibility of the contrast media in the sleeve, the apparatus can be guided to the exact position. The sleeve can incorporate a tube within the contrast media filled sleeve to insert the biopsy needle and to push this needle forward into the prostate. The subject apparatus can utilize various mechanical means to stereotactically move the needle or needle sleeve in various directions. Excerpt(s): The subject invention pertains to a method and apparatus for MR-guided biopsy. The subject invention can be applied to prostate biopsy. In a specific embodiment, the subject invention relates to a stereotactic positioning device for MRguided interventions, such as biopsies of suspicious areas of the prostate gland. MRI (magnetic resonance imaging) is a current radiological imaging modality to view soft tissue lesions of the human body. MR can be used to guide the subject positioning device to directly puncture lesions in the prostate and/or to biopsy these. Prostate cancer is the most common cancer, excluding skin cancers, in American men. The American Cancer Society estimates that during 2002 about 189,000 new cases of prostate
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cancer will be diagnosed in the United States. Accurate determination of the extent of local disease in the prostate is difficult. Current imaging techniques include, for example, transrectal ultrasound (TRUS), endorectal coil magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopic imaging (MRSI). The reported accuracy of TRUS for determining if prostate cancer is confined within the capsule varies widely from 58% to 90%. However, preliminary data from recent studies of endorectal MRI show higher accuracy (75-90%) than TRUS, and better consistency. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and apparatus for needle placement and entry point determination in percutaneous procedures Inventor(s): Bascle, Benedicte; (Plainsboro, NJ), Geiger, Bernhard; (Plainsboro, NJ), Navab, Nassir; (Plainsboro, NJ) Correspondence: Michele L. Conover; Siemens Corporation; Intellectual Property Department; 170 Wood Avenue South; Iselin; NJ; 08830; US Patent Application Number: 20040078045 Date filed: October 10, 2003 Abstract: A method for determining the best entry point for a percutaneous procedure, such as with a biopsy needle, comprises selecting first and second arbitrary entry points on a patient; determining the three dimensional (3-D) orientation of the needle at the first arbitrary entry point for pointing the needle at the primary target; determining the 3-D orientation of the needle: at the first arbitrary entry point for pointing the needle at the secondary target; determining the 3-D dimensional orientation of the needle at the second arbitrary entry point for pointing the needle at the primary target; determining the 3-D orientation of the needle at the second arbitrary entry point for pointing the needle at the secondary target; determining a 3-D line representing the intersection of a first plane containing the first arbitrary entry point, the primary target point, and the secondary target point, and a second plane containing the second arbitrary entry point, the primary target, and the secondary target point, whereby the 3-D line provides a position and orientation for the needle for performing needle biopsy of the primary target through the secondary target. Excerpt(s): The present invention relates to the field of percutaneous procedures and, more specifically, to method and apparatus for needle placement, such as for needle biopsy, and for determining an appropriate entry point for such a needle. Reference is hereby made to copending Provisional Application No. 60/212,199 filed on Jun. 16, 2000 in the names of Benedicte Bascle, Nassir Navab, and Bernhard Geiger and entitled "METHOD FOR NEEDLE PLACEMENT IN A FIXED NUMBER OF ITERATIONS USING PERSPECTIVE INVARIANTS AND METHOD FOR DETERMINING THE BEST ENTRY POINT FOR PERCUTANEOUS PROCEDURES", whereof the disclosure is herein incorporated by reference. Reference is also herein made to the following documents whereof the disclosure is herein incorporated by reference: U.S. Pat. No. 6,028,912 "APPARATUS AND METHOD FOR POINT RECONSTRUCTION AND METRIC MEASUREMENT ON RADIOGRAPHIC IMAGES"; U.S. Pat. No. 5,930,329 "APPARATUS AND METHOD FOR DETECTION AND LOCALIZATION OF A BIOPSY NEEDLE OR SIMILAR SURGICAL TOOL IN A RADIOGRAPHIC IMAGE"; and pending U.S. patent application Ser. No. 09/408,929, Attorney Docket No. 99P7849, entitled "METHOD AND APPARATUS FOR VISUAL SERVOING OF A LINEAR APPARATUS" and filed on 30 Sept. 1999 in the name of inventor Benedicte Bascle.
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Method and apparatus for ultrasound imaging of a biopsy needle or the like during an ultrasound imaging examination Inventor(s): Cerofolini, Marino; (Subbiano, IT), Greppi, Barbara; (Fiesole, IT) Correspondence: Woodard, Emhardt, Naughton, Moriarty And Mcnett; Bank One Center/tower; Suite 3700; 111 Monument Circle; Indianapolis; IN; 46204-5137; US Patent Application Number: 20040002653 Date filed: October 8, 2002 Abstract: A method and apparatus for ultrasound imaging of a biopsy needle or the like during an ultrasound imaging examination, including the steps of alternately performing one or more imaging scans with ultrasound transmit and receive parameters which are adapted for optimized imaging and visualization of the needle and one or more imaging scans with ultrasound transmit and receive parameters adapted for optimized imaging and visualization of the body, in which the needle is inserted, injecting contrast agents in the region to be examined before imaging, and setting ultrasound transmit and receive parameters adapted for optimized imaging and visualization of the body. Excerpt(s): The present patent application is a continuation-in-part patent application of U.S. Ser. No. 10/180,881, filed Jun. 26, 2002, now pending. The invention relates to a method and apparatus for ultrasound imaging of a biopsy needle or the like during an ultrasound imaging examination, including the steps of alternately performing one or more imaging scans with ultrasound transmit and receive parameters which are adapted for optimized imaging and visualization of the needle and one or more imaging scans with ultrasound transmit and receive parameters adapted for optimized imaging and visualization of the body or details thereof, in which the needle is inserted. This method is used to monitor the position of a biopsy needle inside the human body, before removing a sample of tissue. The needle and the surrounding tissue are imaged in real time for an easier control of the needle orientation and proper depth, to remove the tissue from the predetermined location. Obviously, the best position of the needle is the one in which both the instrument and the tissue are best imaged. Unfortunately, the tissue and the instrument are reflectors having totally different characteristics, which require different settings of ultrasound imaging parameters. This is also due to the fact that the needle is a specular reflector, i.e. reflects ultrasonic waves like a mirror. Hence, as the distance from the ultrasound beam incident on the needle to the perpendicular of the needle increases, the energy reflected toward the probe decreases. Nevertheless, these conditions contrast with the optimized setting conditions for tissue imaging. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for evaluating a tissue or biopsy sample to determine if the sample is earlystage melanoma Inventor(s): Alani, Rhoda M.; (Baltimore, MD), Busam, Klaus J.; (Chatham, NJ), Young, Alison Z.; (Baltimore, MD) Correspondence: Oppedahl And Larson Llp; P O Box 5068; Dillon; CO; 80435-5068; US Patent Application Number: 20040014114 Date filed: June 3, 2003 Abstract: A tissue or biopsy sample is evaluated to determine if the sample is earlystage melanoma by determining the level of inhibitor of DNA-binding protein 1 (Id1) expression in cells of the sample; and comparing the determined amount of Id1 to a reference level. The presence of levels of Id1 in cells of the sample in excess of the reference level indicates that the sample is early-stage melanoma. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/386,298, filed Jun. 5, 2003, which is incorporated herein by reference. This application relates to a method for evaluating a tissue of biopsy sample to determine if the sample is early stage melanoma. The method relies on the observation that Id1 protein, one of a class of Id proteins which inhibit DNA binding by transcriptional regulatory proteins, is expressed in early stage melanomas, but not in benign specimens nor in invasive or metastatic melanomas. In tumors with in situ and invasive portions, only the in situ part of the tumor expresses Id1. It has previously been shown in Published PCT Application WO97/0528, which is incorporated herein by reference, that Id proteins, or the nucleic acids encoding such proteins, can serve as diagnostic markers for identifying tumors which may be susceptible to treatment by chemotherapy and radiation. This patent shows data suggesting the ability to use Id1 to distinguish between rhabdomyosarcoma (RMS) and normal muscle cells, but offers no insight concerning melanoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for growth of human conjunctival tissue equivalents for research, clinical ocular surface transplantation and tissue engineering Inventor(s): Ang, Leonard; (Singapore, SG), Beuerman, Roger; (New Orleans, LA), Tan, Donald; (Singapore, SG) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040009590 Date filed: March 31, 2003 Abstract: The invention relates to materials and methods for producing equivalents of tissues of the ocular surface, especially conjunctival tissue equivalents. The method of the invention involves biopsy of an appropriate tissue, primary culture in a certain medium, proliferative culture in a second medium, and differentiative culture in a third medium. The tissue equivalents are typically grown upon a substrate, typically amniotic membrane, which provides ease of handling as one advantage. Excerpt(s): The present invention relates to a method for culturing conjunctival stem cells in vitro to form conjunctival epithelial tissue equivalents by expanding the explanted conjunctival stem cells and then differentiating them in culture. The present invention also relates to culture media for supporting such a method. The present
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invention also encompasses methods for treating eye disorders by transplanting tissue equivalents comprising conjunctival epithelial cells. R. J. -F. Tsai et al. (NEJM 343:86 (2000), I. R. Schwab et al. (Cornea 19:421 (2000) and G. Pellegrini et al. (The Lancet 349:990 (1997)) describe transplanting limbal stem cells for diseases arising from limbal stem cell deficiency to restore corneal epithelial integrity. The Tsai paper mentions that conjunctival epithelial cells are an integral part of the eye surface, but Tsai et al. and other papers on limbal stem cell transplantation indicate that (i) the conjunctival and corneal cell types are quite different in function and morphology, with the limbal cells being the progenitor of corneal cells; and (ii) to achieve regeneration of the corneal surface, the important stem cell type to transplant is the limbal stem cell. Tsai et al. and others fail to suggest that conjunctival epithelium is useful in restoring the corneal surface. The limbal stem cell is indeed an important factor in restoring the corneal surface, but conjunctival stem cells are important in preventing limbal stem cell and corneal epithelial damage in the first place. This is due to the supportive function of conjunctival stem cells, which is important to regeneration and restoration of the ocular surface. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for obtaining characterised muscle-derived cell populations and uses Inventor(s): Marolleau, Jean-Pierre; (Le Perreux, FR), Robert, Isabelle; (Saint-Ouen, FR), Ternaux, Brigitte; (Villepreux, FR), Tremblay, Jacques; (Quebec, CA), Vilquin, JeanThomas; (Chelles, FR) Correspondence: Robert M. Schulman; Hunton & Williams; Suite 1200; 1900 K Street, N.W.; Washington; DC; 20006-1109; US Patent Application Number: 20040043008 Date filed: December 9, 2002 Abstract: A method for obtaining cell populations derived from the muscular tissue and their use for preparing cell therapy products includes culturing cells previously removed by biopsy from skeletal muscular tissues, identifying the different types of cells present at different stages of culture, selecting the culture stage on the basis of the required cell population and collecting the selected culture stage for preparing a cell therapy product. The invention also concerns cell populations derived from muscular tissue obtained by implementing the method whereof the dominant cell type is CD34+, CD15+ or CD56+ or Class 1+ HLA, or comprises a doubly negative CD56-/CD15- cell type or may comprise more minority CD10+, Stro-1+ and CD117+ cell types. Excerpt(s): The present invention concerns cell populations derived from muscle tissue and their use in the preparation of cell therapy products. More specifically, the invention concerns a method of obtaining cell populations and their use for reconstituting the hematological and immunological system, and the bone, adipose, cartilage, muscle or vascular tissues. Cell therapy is a method with promising potential for the treatment of many diseases. The principle of cell therapy is based on the possibility of reconstituting damaged tissue or of restoring a biological function that has been lost or impaired within a tissue, from specific cells cultured ex vivo and transplanted onto the sick tissue. Another interest of cell therapy is that the transplanted cells can be used as a platform for delivering a biologically active product, if necessary after genetic modification of the cells before transplantation. Many trials of cell therapy have been reported using primary cultures of different cell types. We could mention the transplantations of neuronal cells carried out to treat Huntingdon's chorea (1) or
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Parkinson's disease (2), transplantations of Islet of Langerhans cells to treat diabetes (3) or transplantations of myoblastic cells carried out to treat Duchenne's muscular dystrophy (4, 5, 6, 7) or, after genetic modification of the cells, for the treatment of dwarfism (8), hemophilia (9) and Parkinson's disease (10). Skeletal muscle is regenerated by the satellite cells, which are mononucleate myogenic cells located under the basal layer of the muscle fibers. Following a lesion, these cells quit a quiescent state and embark on a phase of active proliferation and are known subsequently as myoblasts. Subsequently, the myoblasts fuse to form myotubes. There have been attempts in man to transplant myoblasts to treat Duchenne's muscular dystrophy and Becker's muscular dystrophy (4, 6, 7, 11). The functional effect of the transplantations described in these studies remains limited, but no side effect has been reported in terms of infection or carcinogenesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for reducing psa levels Inventor(s): Fisch, Harry; (Scarsdale, NY) Correspondence: Ira J Schaefer; Clifford Chance; 200 Park Avenue; New York; NY; 10166; US Patent Application Number: 20040043970 Date filed: March 21, 2003 Abstract: A method for reducing an antigen indicator of prostate cancer and for reducing the need for biopsies in men suspected of having prostate cancer and a method for treating patients with elevated PSA levels. In one method, the level of an antigen indicator of prostate cancer is measured and for an above normal level of the antigen indicator, an effective amount of an anti-inflammatory, or a combination of the anti-inflammatory and an antibiotic, is administered and the level of the antigen indicator is remeasured to determine if the level is normal or reduced, whereby a biopsy may not be indicated. Excerpt(s): This application claims priority to PCT/US02/29713 filed Sep. 19, 2002 and now pending which claims priority to U.S. Provisional Patent Application No. 60/340,909 filed Oct. 29, 2001 and now expired and U.S. Provisional Patent Application No. 60/351,157 filed Jan. 23, 2002 and now expired. The present invention relates to methods for reducing PSA levels and the need for a biopsy in men suspected of having prostate cancer and for treating patients with elevated PSA levels. Prostate specific antigen (PSA) is a low molecular weight glycoprotein of approximately 30 kilodaltons (kD) produced mainly by prostatic glandular epithelial cells. PSA is a member of the human tissue kalikrein gene family, which consists of three genes, hKLK1, hKLK2, and hKLK3. The protein product of these genes are pancreatic-kidney kallikrein (hK1), human glandular kallikrein (hK2) (previously known as hGK-1), and PSA (hK3). PSA is a serine protease and exhibits a chymotrypsin-like specificity cleaving at a hydrophobic residue (see Chu et al., J. Urol. 141:152-56 (1989)). The other two kallikreins have trypsinlike specificity. These three genes are located on chromosome 19. The expression of both PSA and hK2 are under androgen control. The protein for hK2 has not been isolated, and its potential clinical utility has not been determined (McCormack et al., Urology 45:729-44 (1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and devices for automated biopsy and collection of soft tissue Inventor(s): Burbank, Fred H.; (San Juan Capistrano, CA), Galt, Kenneth M.; (Seal Beach, CA), Ritchart, Mark A.; (Murrieta, CA), Stuart, J. Michael; (Lake Forest, CA) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040019299 Date filed: February 11, 2003 Abstract: Instruments for performing percutaneous biopsy procedures are disclosed, which have advantageous features for improving functionality and performance over prior art devices. These instruments comprise two types, single-use devices, and multiple-use devices having active tissue capture capability. Improved features include the ability to retrieve and evaluate multiple tissue samples during a single insertion procedure, without physical handling of the samples, as well as constructional features, such as a molded tissue cassette housing, variant vacuum port embodiments suited for different tissue environments, and a method for backflushing the instrument to remove biological debris, among others. Excerpt(s): This application is a continuation-in-part of co-pending parent application Ser. No. 08/217,246, filed. Mar. 24, 1994. The present invention relates to methods and devices for tissue sampling, and more specifically to improved biopsy intents and methods for acquiring subcutaneous biopsies and for removing lesions. It is often desirable and frequently necessary to sample or test a portior tissue from humans and other animals, particularly in the diagnosis and treatment of patients with cancerous tumors, pre-malignant conditions, and other diseases or disorders. Typically, in the case of cancer, when the physician establishes by means of procedures such as palpation, xray, or ultrasound imaging that suspicious cancers exist, a biopsy is performed to determine whether the cells are cancerous. Biopsy may be done by an open or percutaneous technique. Open biopsy, which is an invasive surgical procedure using a scalpel and involving direct vision of the target area, removes the entire mass (excisional biopsy) or a part of the mass (incisional biopsy). Percutaneous biopsy, on the other hand, is usually done with a needle-like instrument through a relatively small incision, blindly or with the aid of an artificial imaging device, and may be either a fine needle aspiration (FNA) or a core biopsy. In FNA biopsy, individual cells or clusters of cells are obtained for cytologic examination and may be prepared such as in a Papanicolaou smear. In core biopsy, as the term suggests, a core or fragment of tissue is obtained for histologic examination which may be done via a frozen section or paraffin section. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and devices for defining and marking tissue Inventor(s): Burbank, Fred H.; (San Juan Capistrano, CA), Foerster, Seth A.; (San Clemente, CA), Ritchart, Mark A.; (Murrieta, CA), Zerbouni, Elias A.; (Baltimore, MD) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040024304 Date filed: July 30, 2003
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Abstract: In order to later identify the location of a biopsy or surgery, various means and methods for permanently and non-surgically marking selected tissue in the human body are used. Later visualization of the markers is readily accomplished using state-ofthe-art imaging systems. Excerpt(s): This invention relates to methods and devices for marking and defining particular locations in human tissue, and more particularly relates to methods and devices for permanently defining the location and margins of lesions detected in a human breast. It is desirable and often necessary to perform procedures for detecting, sampling, and testing lesions and other abnormalities in the tissue of humans and other animals, particularly in the diagnosis and treatment of patients with cancerous tumors, pre-malignant conditions and other diseases or disorders. Typically, in the case of cancer, when a physician establishes by means of known procedures (i.e. palpation, xray, MRI, or ultrasound imaging) that suspicious circumstances exist a biopsy is performed to determine whether the cells are cancerous. Biopsy may be an open or percutaneous technique. Open biopsy removes the entire mass (excisional biopsy) or a part of the mass (incisional biopsy). Percutaneous biopsy on the other hand is usually done with a needle-like instrument and may be either a fine needle aspiration (FNA) or a core biopsy. In FNA biopsy, very small needles are used to obtain individual cells or clusters of cells for cytologic examination. The cells may be prepared such as in a Papanicolaou (Pap) smear. In core biopsy, as the term suggests, a core or fragment of tissue is obtained for histologic examination which may be done via a frozen section or paraffin section. The chief difference between FNA and core biopsy is the size of the tissue sample taken. A real time or near real time imaging system having stereoscopic capabilities, such as the stereotactic guidance system described in U.S. Pat. No. 5,240,011, is employed to guide the extraction instrument to the lesion. Advantageous methods and devices for performing core biopsies are described in the assignee's copending patent application Ser. No. 08/217,246, filed on Mar. 24, 1994, and herein incorporated by reference. Often, the lesion is merely a calcification derived from dead abnormal tissue, which may be cancerous or pre-cancerous, and it is desirable to remove only a sample of the lesion, rather than the entire lesion, to evaluate it. This is because such a lesion actually serves to mark or define the location of adjacent abnormal tissue, so the physician does not wish to remove the entire lesion and thereby lose a critical means for later re-locating the affected tissue. One of the benefits to the patient from core biopsy is that the mass of the tissue taken is small. However, oftentimes, either inadvertently or because the lesion is too small, the entire lesion is removed for evaluation, even though it is desired to remove only a portion. Then, if subsequent analysis indicates the tissue to be malignant (malignant tissue requires removal, days or weeks later, of tissue around the immediate site of the original biopsy), it is difficult for the physician to determine the precise location of the lesion, in order to perform necessary additional procedures on adjacent potentially cancerous tissue. Additionally, even if the lesion is found to be benign, there will be no evidence of its location during future examinations, to mark the location of the previously removed calcification so that the affected tissue may be carefully monitored for future reoccurrences. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Micro-invasive breast biopsy device Inventor(s): Pflueger, D. Russell; (San Juan Capistrano, CA) Correspondence: Frank J. Uxa; Stout, Uxa, Buyan & Mullins, Llp; Suite 300; 4 Venture; Irvine; CA; 92618; US Patent Application Number: 20040059254 Date filed: September 22, 2003 Abstract: An apparatus for removing tissue and/or other material from a patient, particularly a breast of a patient, is provided. The apparatus generally includes a handpiece and a tissue removal mechanism connected thereto. The tissue removal mechanism includes a cannula having an open distal tip and an outer diameter of less than about 5 mm, or less than about 2 mm. The mechanism further includes a rotatable element having a distal portion with helical threading. The distal portion of the rotatable element extends beyond the open distal tip of the cannula in order to allow tissue to prolapse between turns of the helical threading. The apparatus is designed to draw soft tissue into the cannula upon rotation of the rotatable element and without the need for supplemental sources of aspiration. Excerpt(s): This application claims the benefit of U.S. provisional applications Serial No. 60/278,128, filed Mar. 23, 2001 and Serial No. 60/281,848, filed Apr. 5, 2001 and Serial No. 60/305,178 filed Jul. 13, 2001 and Serial No. 60/322,909, filed Sep. 17, 2001 and Serial No. 60/342,436, filed Dec. 21, 2001, the disclosure of each of which is incorporated in its entirety herein by reference. The present invention relates generally to medical devices, and, more particularly, to micro-invasive devices and methods for removing breast tissue for biopsy and treatment. The medical industry is constantly evolving through the adaptation of improved pharmaceutical, biotechnology, and medical device products and procedures. Techniques and technologies are being developed to treat internal areas of the body through less invasive means. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Monoclonal antibody for Nkx3.1 and method for detecting the same Inventor(s): Abate-Shen, Cory; (Warren, NJ), Kim, Minjung; (Piscataway, NJ), Shen, Michael M.; (Warren, NJ) Correspondence: Richard R. Muccino, ESQ.; 758 Springfield Avenue; Summit; NJ; 07901; US Patent Application Number: 20040002086 Date filed: February 13, 2003 Abstract: The present invention pertains to a monoclonal antibody, or fragment thereof, having an antigen-binding specific region for NKX3.1 and to a hybridoma cell line for producing the monoclonal antibody. The present invention also pertains to a method for detecting the presence of NKX3.1 in a sample. The method comprises (a) contacting a biopsy tissue sample with a monoclonal antibody, or a fragment thereof, having an antigen-binding specific region for NKX3.1, under conditions permitting immunospecific binding between the monoclonal antibody, or a fragment thereof, and NKX3.1 in the sample; and (b) detecting whether immunospecific binding has occurred to detect the presence of NKX3.1 in the sample.
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Excerpt(s): This application is a continuation of U.S. pat. app. Ser. No. 09/853,121, filed May 10, 2001. The present invention pertains to a monoclonal antibody, or fragment thereof, having an antigen-binding specific region for NKx3.1 and to a hybridoma cell line for producing the monclonal antibody. The present invention also pertains to a method for detecting the presence of NKx3.1 in a sample. The method comprises (a) contacting a biopsy tissue sample with monoclonal antibody, or a fragment thereof, having an antigen-binding specific region of NKx3.1, under conditions permitting immunospecific binding between the monoclonal antibody, or a fragment thereof, and NKx3.1 in the sample and (b) detecting whether immunospecific binding has occurred to detect the presence of Nkx3.1 in the sample. The disclosures referred to herein to illustrate the background of the invention and to provide additional detail with respect to its practice are incorporated herein by reference and, for convenience, are referenced in the following text and respectively grouped in the appended bibliography. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multiple biopsy apparatus and related method of use Inventor(s): McAlister, Gary; (Franklin, MA), Sanders, Paul; (Raleigh, NC) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20040034310 Date filed: April 11, 2003 Abstract: An endoluminal biopsy device is provided with a proximal actuation mechanism attached to a distal sampler by at least one elongate member. The distal sampler includes a distal inner portion defining a plurality of chambers, each configured to receive a tissue sample, and a distal outer portion defining a cutting mechanism opening having a cutting edge adjacent the cutting mechanism opening. The distal outer portion is configured so that, when the cutting mechanism opening aligns with one of the plurality of chambers, the distal outer portion covers the remaining chambers. A related method for the use of such an endoluminal biopsy device also is provided. Excerpt(s): The present invention relates to a biopsy device for use in endoluminal procedures. More particularly, the present invention relates to a biopsy device that is capable of taking multiple biopsies. An endoluminal procedure is a medical procedure that takes place in one of the many tubes, or lumens, within the human body. These endoluminal procedures may take place in vascular, gastrointestinal, or air exchange lumens and may involve disease diagnosis and/or treatment. Millions of endoluminal procedures are performed each year in hospitals around the world. Endoluminal procedures are often performed utilizing a device known as an endoscope. An endoscope is a tube, either rigid or flexible, that is introduced through a lumen (opening) in the human body, such as the mouth or rectum. The endoscope may simply be used to hold open the lumen for examination, but it may also carry light(s), visioning system(s), or other tools to be used in the procedure. An open or "working" channel is usually present within the endoscope into which the endoscopist can insert and withdraw a myriad of endoluminal diagnostic or treatment devices. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Rotator cuff repair using engineered tissues Inventor(s): Ferree, Bret A.; (Cincinnati, OH) Correspondence: Gifford, Krass, Groh, Sprinkle; Anderson & Citkowski, PC; 280 N Old Woodard Ave; Suite 400; Birmingham; MI; 48009; US Patent Application Number: 20040093092 Date filed: June 13, 2002 Abstract: Living fibrocytes are combined with rotator cuff extracellular matrix obtained from recently deceased human or animal donors to eliminate pain in patients with tendonitis and other rotator cuff deficiencies. According to the method, fibrocytes from a living donor, preferably the patient, and rotator cuff tissue is harvested from a recently deceased human or animal donor in a manner which retains the extracellular matrix. The harvested cells are combined with the extracellular matrix to produce an engineered rotator cuff tissue, which is then transplanted into or onto a patient's rotator cuff to be repaired. Additional therapeutic substances such as culture medium, growth factors, differentiation factors, hydrogels, polymers, antibiotics, anti-inflammatory medications, or immunosuppressive medications could be added to the transplanted annulus fibrosis tissue. In like fashion, the processes described herein may be used to repair or replace other tissues or organs of the body such as the pancreas, liver, kidney, heart, etc. Healthy live cells would be obtained thorough biopsy and tissue culture. The live cells would be added to the extracellular matrix of tissues or organs harvested to recently deceased human or animals. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/688,716, filed Oct. 16, 2000, which claims priority from U.S. provisional patent application Serial No. 60/159,488, filed Oct. 14, 1999; and is also a continuation-in-part of U.S. patent application Ser. No. 09/415,382, filed Oct. 8, 1999. The entire content of each application is incorporated herein by reference. This invention relates generally to rotator cuff repair, and more particularly, to the use of engineered tissues in conjunction with such treatment. Intervertebral discs provide mobility and a cushion between the vertebrae. At the center of the disc is the nucleus pulposus. The nucleus pulposus is surrounded by the annulus fibrosis, which is comprised of cells (fibrocyte-like and chondrocyte-like), collagen fibers, and non-fibrillar extracellular matrix. The components of the annulus are arranged in 15-25 lamellae around the nucleus pulposus. The fibers in the lamellae alternate their direction of orientation by 30 degrees between each band. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Soft tissue orientation and imaging guide systems and methods Inventor(s): Lee, Roberta; (Redwood City, CA) Correspondence: Jung-Hua Kuo; Attorney AT Law; PO Box 3275; Los Altos; CA; 94024; US Patent Application Number: 20040087851 Date filed: October 31, 2002 Abstract: Systems and methods for the orientation of soft tissue such as breast tissue for enhanced accuracy of imaging and/or procedures such as a biopsy or excision are disclosed. The system for orientating and maintaining the orientation of soft tissue
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generally includes a frame defining an opening, the frame being configured to orient and immobilize an area of soft tissue positioned on one side of the opening, an attachment mechanism to secure the frame to an attachment region defined by the area of soft tissue or by a skin surface overlying the area of soft tissue, to facilitate orienting and immobilizing the area of soft tissue, and an imaging device to image the area of soft tissue. The opening may allow a probe of the imaging device or imaging energy transmitted by the imaging device to be movable therein for image scanning of the soft tissue. The probe, e.g., an ultrasound transducer can be rotated within the frame such that the probe scans at least either of two perpendicular directions within the frame. The frame may be adjustable in at least one dimension in order to adjust the size of the frame opening so as to facilitate the scanning and positioning of the probe within the frame opening. The frame may be attached and secured to the soft tissue with vacuum, adhesive, and/or clips or hooks. The soft tissue may be stretched into a desire orientation prior to attachment of the frame. An anchored lift member may be connected to the frame so as to slightly lift the frame and thus position and immobilize the soft tissue to which the frame is attached. Lifting of the soft tissue improves and enhances a tissue separation process using a tissue separation device. A connector may connect the imaging device to the tissue separation device to maintain a portion of the tissue separation device within the image plane of the probe to further improve and enhance the tissue separation process. Excerpt(s): The present invention relates generally to systems and methods for positioning and maintaining a region of soft tissue in a desired orientation to facilitate imaging, and the performance of a procedure in the soft tissue. More specifically, systems and methods for the orientation of soft tissue such as breast tissue for enhanced accuracy of imaging and/or procedures such as a biopsy or excision are disclosed. Before a lesion within breast tissue of a living subject can be properly targeted and treated, the breast tissue is often imaged in order to locate and delineate the lesion. Once the location of the lesion is determined, it is often necessary to insert an invasive device such as a guide wire into the breast tissue to target the lesion. Ideally, the tip of the guide wire is placed near the lesion within the breast tissue. The guide wire helps direct the surgeon to the lesion during an operative procedure. There are several disadvantages in such a procedure using the guide wire. For example, using a guide wire is a cumbersome and time consuming process. The pre-operative guide wire placement is typically performed in a separate department from the operative procedure, often adding hours of time. In addition, the guide wire can move within the breast before the operative procedure is conducted. Further, only a rough estimate of the actual location of the tip of the guide wire within the breast tissue can be made prior to making the skin incision which often leads to inaccurate or excessive tissue excision. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Surgical biopsy device Inventor(s): Defonzo, Stephen A.; (Wayne, PA), Hinchliffe, Peter W.J.; (Dowington, PA), McGuckin, James F. JR.; (Radnor, PA) Correspondence: Rex Medical, L.P.; Suite 6101; 555 North Lane; Conshohocken; PA; 19428; US Patent Application Number: 20040087942 Date filed: August 15, 2003
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Abstract: A surgical biopsy apparatus for cutting tissue comprising a housing having a longitudinal axis, first and second members movable from a retracted position to an extended position with respect to the housing, a third member slidably positioned and extendable with respect to the first member, a fourth member slidably positioned and extendable with respect to the second member, and an electrocautery cutting wire slidable with respect to the third and fourth members to surround a region of tissue positioned between the third and fourth members to cut the tissue. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/122,185, filed Jul. 23, 1998 which claims priority from U.S. provisional application No. 60/053,664, filed Jul. 24, 1997. The contents of both these applications are incorporated herein by reference. This application relates to a surgical device for removing tissue and more particularly relates to a surgical tissue biopsy device insertable through a small incision in the body. Over 150,000 women in the United States alone are diagnosed each year with breast cancer. A biopsy of breast tissue is indicated when a breast abnormality is found, allowing removal of the tissue and testing to determine whether the abnormality is malignant and further surgery is necessary. Early diagnosis and removal of cancerous tissue is critical for successful treatment as early detection greatly increases the chances of survival. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Surgical device for the collection of soft tissue Inventor(s): Buzzard, Jon D.; (Milford, OH), Hibner, John A.; (Mason, OH), Iverson, David S.; (Chicago, IL), Piller, Michael E.; (Cincinnati, OH), Privitera, Salvatore; (West Chester, OH), Reiter, Michael J.; (Oak Park, IL) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040034280 Date filed: August 11, 2003 Abstract: A handheld biopsy device is provided for the collection of soft tissue samples from a surgical patient. In a preferred embodiment, the biopsy device comprises a handpiece, a fluid collection system, and a power transmission source. The handpiece is configured for grasping by a single hand, and being independently manipulatable by hand for movement of the instrument toward and away from the patient. An elongated piercer extends from the distal end of the handpiece. The piercer has a sharpened distal end for entering the tissue and a port located proximal to the sharpened distal end for receiving a portion of tissue mass. An elongated cutter is disposed coaxially relative to a piercer lumen of the piercer. A distal blade of the cutter slides distally past the port of the piercer to severe the tissue portion drawn into the port by vacuum. The cutter is retracted to a most proximal position for removal of the tissue portion from a cutter lumen of the cutter. The handpiece further comprises a holster for detachably connecting a cutter rotational transmission and a cutter axial transmission to the power transmission source. Excerpt(s): This application is related to the following co-pending U.S. patent applications: Ser. No. 08/825,899 filed on Apr. 2, 1997; Ser. No. 09/107,845 filed on Jun. 30, 1998. This application is further related to the following co-pending U.S. patent applications: Ser. No. ______, filed (Attorney Docket No. END 562); Ser. No. ______, filed (Attorney Docket No. END 563). The present invention relates, in general, to
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devices for tissue sampling and, more particularly, to improved biopsy probes for acquiring subcutaneous biopsies and for removing lesions. Generally there are two ways to obtain percutaneously a portion of tissue from within the body, by aspiration or by core sampling. Aspiration of the tissue through a fine needle requires the tissue to be fragmented into pieces small enough to be withdrawn in a fluid medium. The method is less intrusive than other known sampling techniques, but one can only examine cells in the liquid (cytology) and not the cells and the structure (pathology). In core biopsy, a core or fragment of tissue is obtained for histologic examination which may be done via a frozen or paraffin section. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Tissue biopsy and processing device Inventor(s): Binette, Francois; (Weymouth, MA), Hwang, Julia; (Watertown, MA), McRury, Ian D.; (Medway, MA) Correspondence: Nutter Mcclennen & Fish Llp; World Trade Center West; 155 Seaport Boulevard; Boston; MA; 02210-2604; US Patent Application Number: 20040097829 Date filed: November 15, 2002 Abstract: A tissue biopsy and processing device for capturing and processing a tissue sample is provided. In general, the device includes a biopsy member adapted to remove a tissue sample from a patient's body, and a processing apparatus adapted to receive the tissue sample from the biopsy device, and to dissociate and mince the tissue sample in preparation for further use. The processing apparatus can include a tissue reducing chamber in communication with and adapted to receive the tissue sample from the biopsy member, and a tissue processing element associated with the tissue reducing chamber that is effective to dissociate the tissue sample retained within the tissue reducing chamber. Excerpt(s): The present invention relates generally to tissue biopsy and processing devices. Bone grafts are often used to treat fractures, gaps in bones caused by trauma or infection, revision joint surgery, and oral/maxillofacial surgery. Bone grafts provide a framework into which the host bone can regenerate and heal. Once implanted, the bone cells weave into and through the porous microstructure of the bone graft to support the new tissue, blood cells and soft tissue as they grow to connect fractured bone segments. The loss or failure of tissue is one of the most frequent and costly problems in human health care. In recent years, grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living replacements. Tissue engineering enables the growth of transplantable functional tissue replacements starting from samples of autologous cells of the patient. The cells are obtained by harvesting tissue from a patient using a biopsy and then cells are extracted from the tissue sample and cultured to the appropriate numbers in the laboratory. These living cells are then placed in a three-dimensional natural or synthetic scaffold or matrix, and are kept under tissue specific culture conditions to ensure differentiation and tissue maturation. If provided with the appropriate conditions and signals, the cells will secrete various matrix materials to create an actual living tissue that can be used as a replacement tissue to be implanted back into the defective site in the patient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Ultrasound endoscope Inventor(s): Kohno, Shinichi; (Saitama, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20040082883 Date filed: October 16, 2003 Abstract: A rigid tip end section which is connected to an angle section at the fore distal end of an insertion instrument of an ultrasound endoscope is housed in a casing which can be split into a main casing and a separable head block to facilitate maintenance and service of internal component parts of the rigid tip end section. An ultrasound transducer is accommodated in a front side portion of the main casing, while endoscopic observation means including an illumination means and an optical image pickup means are fitted in an inclined wall rising obliquely upward on the rear side of the ultrasound transducer. An outlet opening of a biopsy channel outlet passage is located between the ultrasound transducer and the endoscopic observation means. The main casing is adapted to accommodate the ultrasound transducer and its wiring, while the separable head block is adapted to accommodate at least part of component parts of the endoscopic observation means. The main casing and the separable head block are joined with each other through joint wall portions provided along split lines at the opposite lateral sides and at the front side thereof. A foremost one of angle rings of the angle section is detachably fitted on base end portions of the main casing and separable head block to retain these parts in a fixedly connected state. Excerpt(s): This invention relates to an ultrasound endoscope which is capable of both endoscopic and ultrasound examinations in body cavities, and more particularly to an ultrasound endoscope which is arranged to facilitate maintenance and service such as inspection, repair and replacements of internal component parts within a rigid tip end section at the distal end of an insertion instrument of an ultrasound endoscope. Generally, ultrasound endoscopes are provided with an endoscopic observation means including an illumination window and an observation window on a rigid tip end portion at a distal end of an elongated insertion instrument along with an ultrasound examination means such as an ultrasound transducer. After introducing the insertion instrument into a body cavity, an intracavitary site of interest is firstly examined by the endoscopic observation means, and then the ultrasound examination means is used to further examine tissues in a diseased portion or a suspicious portion which has been spotted as a result of the endoscopic examination. In many cases, the so-called biopsy channel is provided in and through the endoscopic insertion instrument for forceps or a high frequency surgical or biopsy instrument to be introduced into a body cavity and operated under observation through the endoscopic observation means or for a puncture needle or other puncture instrument to be operated under observation through ultrasound scan images. Connected to the base end of the insertion instrument of the ultrasound endoscope is a manipulating head assembly to be gripped by an operator at the time of endoscopic or ultrasound examination. Various operation control buttons and levers are provided on the manipulating head assembly. The insertion instrument has an elongated flexible body which can be bent easily along the shape of a path of insertion, and an angle section and a rigid tip end section are successively connected to the fore end of the elongated flexible body. The above-mentioned endoscopic observation means, ultrasound examination means and biopsy channel are provided on the rigid tip end section. Accordingly, by operating the manipulating head
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assembly to turn the angle section in an upward, downward, rightward or leftward direction, the rigid tip end section can be turned into an arbitrary direction. 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 biopsy, 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 “biopsy” (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 biopsy. You can also use this procedure to view pending patent applications concerning biopsy. 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 6. BOOKS ON BIOPSY Overview This chapter provides bibliographic book references relating to biopsy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on biopsy 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 “biopsy” (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 biopsy: •
Diagnostic Tests in Nephrology Source: London, England: Arnold. 1999. 297 p. Contact: Available from Oxford University Press. 2001 Evans Road, Cary, NC 27513. (800) 451-7556 or (919) 677-0977. Website: www.oup-usa.org. PRICE: $49.50 plus shipping and handling. ISBN: 034074085X. Summary: Although history taking and examination remain the principal tools of medicine, many patients with renal disorders do not present with clinical features until their disease is advanced. Nephrologists (kidney specialists) depend heavily on investigations (diagnostic tests) from many disciplines in the management of patients with renal disease. This nephrology textbook brings together practical guidance on the range of diagnostic procedures available for the investigation of renal (kidney) disease. The first part of the text covers specific tests used in pathology, including biochemical, hematological, urinalysis, immunological, radiological, nuclear, biopsy, and genetic
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procedures (including gene counseling). The second section of the text reviews renal investigations in clinical practice, with chapters covering the diagnosis of acute renal failure (ARF), chronic renal failure (CRF), transplantation, hypertension (high blood pressure), pregnancy, and pediatric renal disease. The text includes 12 pages of color photographs and a detailed subject index. •
Diseases of the Liver and Biliary System, Eleventh Edition Source: Malden, MA: Blackwell Science, Inc. 2002. 706 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: Designed to serve practicing physicians, surgeons and pathologists, as well as clinical students, this textbook presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The text offers 38 chapters: anatomy and function; the assessment of liver function; biopsy of the liver; the hematology of liver disease; ultrasound, computed tomography (CT scan) and magnetic resonance imaging (MRI); hepatocellular failure; hepatic encephalopathy; acute liver failure; ascites (fluid accumulation); the portal venous system and portal hypertension; the hepatic artery and hepatic vein, and the liver in circulatory failure; jaundice; cholestasis; primary biliary cirrhosis (PBC); sclerosing cholangitis; viral hepatitis, including general features, hepatitis A, hepatitis E, and other viruses; hepatitis B virus and hepatitis Delta virus; hepatitis C virus; chronic hepatitis, its general features and autoimmune chronic disease; drugs and the liver; hepatic cirrhosis (scarring); alcohol and the liver; iron overload states; Wilson's disease; nutritional and metabolic liver diseases; the liver in infancy and childhood; the liver in pregnancy; the liver is systemic disease, granulomas, and hepatic trauma; the liver in infections; nodules and benign liver lesions; malignant liver tumors; the role of interventional radiology and endoscopy in imaging of the biliary tract; cysts and congenital biliary abnormalities; gallstones and inflammatory gallbladder diseases; benign stricture of the bile ducts; diseases of the ampulla of Vater and the pancreas; tumors of the gallbladder and bile ducts; and hepatic transplantation. The text includes full-color and black-and-white illustrations and photographs. A detailed subject index concludes the volume.
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Vanishing Mind: A Practical Guide to Alzheimer's Disease and Other Dementias Source: New York City, NY: W.H. Freeman and Company. 1991. 191 p. Contact: Available from W. H. Freeman and Company. Order Department, 4419 West 1980 South, Salt Lake City, UT 84104. (800) 877-5351. PRICE: $22.95. ISBN: 0716721317. Summary: Directed primarily toward nonprofessionals and affected family members, this book provides an overview of Alzheimer's disease and other dementias and the care of persons with these disorders. Nine chapters cover the following topics: signs and symptoms of dementia; diseases that produce primary dementia (primary undifferentiated dementias and usually differentiated dementias); diseases and conditions associated with secondary dementia (depression, AIDS, blood vessel disease, other secondary dementias, and drugs); what doctors do and how they can help (specialists and tests/procedures, including psychological testing, electroencephalograms, cerebrospinal fluid exams, x-rays and CAT scans, brain biopsy, and autopsy); possible causes of primary dementia (genetic factors, molecular genetics, viruses, neurotransmitters, aluminum, immune system, and hormonal factors); medical
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treatment and management of dementias (Alzheimer's disease, Huntington's disease, general principles); hospitals, nursing homes, and care alternatives; practical matters (legal responsibility, insurance, disability and retirement plans, social security, ethical decisions); and new technologies (positron emitting tomography and magnetic resonance imaging). •
Laparoscopy in Children Source: Heidelberg, Germany: Springer-Verlag. 2003. 147 p. Contact: Available from Springer-Verlag. Tiergartenstr. 17, D-69121 Heidelberg, Germany. (49)6221-487-0. Website: www.springer.de. E-mail:
[email protected]. PRICE: $69.95 plus shipping and handling. ISBN: 3540429751. Summary: Most surgeons are familiar with the techniques of laparoscopic surgery, however, in children there are variations in size and technical approach. This book describes the differences and characteristic aspects of laparoscopy in small children. The book is an atlas of numerous drawings, accompanied by textual descriptions. Technical guidelines are given on how to perform laparoscopy safely, even in small children. Topics include patient selection, anesthesia, insufflation, trocar insertion, instruments, ligating, needle insertion, suturing, adhesiolysis, appendectomy, cholecystectomy (gallbladder removal), cryptorchidism, fundoplication, inguinal hernia, intussusception, liver biopsy, Meckel's diverticulum, ovary, pyloromyotomy, sigmoid resection, splenectomy, varicocele, thoracoscopy, and postoperative care. The aim of the book is to provide surgeons with the knowledge to extend their expertise in adult laparoscopy to children. A subject index concludes the textbook.
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Renal Disease in Children: Clinical Evaluation and Diagnosis Source: Secaucus, NJ: Springer-Verlag. 1990. 528 p. Contact: No longer available from publisher. Summary: The purpose of this book is to provide pediatricians, family physicians, nephrologists, urologists, residents, clinical fellows, and medical students with a complete compendium on the clinical evaluation of renal disease in children. It is meant to be a desk reference to help in the diagnosis of disease and the interpretation of relevant clinical laboratory data; it is not designed to be a textbook. The book covers pediatric nephrology problems classified by mode of investigation (urinalysis, imaging, kidney biopsy, etc.) or presentation (hematuria, proteinuria, urinary tract infection, renal failure, etc.). Detailed discussions of pathophysiology and management of different renal conditions have been omitted; the focus is on workup and diagnosis. Prenatal diagnosis, prevention, and use of the computer in renal disease are briefly discussed. Many tables, algorithms, and formulas are included to assist the reader. A limited number of specific references and a few key general references are included in each chapter to allow the reader to pursue selected areas in depth. Each chapter begins with an outline of the topics to be covered in that chapter. Detailed appendixes include: reference intervals; formulas used in the diagnosis and treatment of various renal conditions; nomograms; and a table of over 400 conditions and syndromes associated with renal involvement. This table presents the main clinical features, renal abnormalities, and hereditary factors for each condition. An extensive subject index is included. 519 references.
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Alzheimer Disease: Current Research in Early Diagnosis Source: New York, NY: Taylor and Francis New York Inc. 1990. 355 p. Contact: This publication may be available from your local library. Call for information. Summary: This book addresses the early clinical diagnosis of Alzheimer's disease. It was written to evaluate the relevance of current research for the early diagnosis of Alzheimer's disease. The book is divided into eight parts: early clinical diagnosis, neuropsychology, neurochemistry, electroencephalogy, neuropharmacology, molecular genetics, brain biopsy, and brain imaging. Each section includes one or more essays addressing specific issues in that area of diagnosis. The early clinical diagnosis section includes essays about NINCDS-ADRDA criteria for early clinical diagnosis, genetics and identifying persons at high risk, and early identification of dementia in the community. The neuropsychology section includes essays about neuropsychological characteristics of early Alzheimer's disease and normal aging versus Alzheimer's disease. Essays addressing diagnosis, markers of cholinergic dysfunction, and EEG in diagnosis form the section on neurochemistry. Neuropharmacology centers on the drug challenge strategies, namely, scopolamine. Biochemical markers in cerebrospinal fluid as a diagnostic test and immunochemical approaches to the diagnosis of Alzheimer's disease are included in the molecular genetics section. The section on brain biopsy includes essays about anatomical criteria for biopsy diagnosis; plaques, tangles and amyloid; and cerebral biopsy in the neurochemical study of Alzheimer's disease. The final section on brain imaging consists of essays addressing CT, MRI, and NMR spectroscopy; positron emission tomography and neuropsychological studies in dementia; visualization of cholinergic tracers in Alzheimer brains in vivo by positron emission tomography; and SPECT studies in Alzheimer type dementia patients.
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Coping with Celiac: The Great Masquerader Source: Gulfport, MS: A and G Publishing. 1998. 152 p. Contact: Available from A and G Publishing. 2907 Palmer Drive, Gulfport, MS 39507. (877) 896-9334. PRICE: $12.99 plus shipping and handling. ISBN: 0966535308. Summary: This book informs the public about problems that people with celiac disease (gluten intolerance) face every day and helps them cope with those problems. Celiac disease is defined as a chronic intestinal malabsorption disorder caused by intolerance to gluten, a cereal protein found in wheat and rye (and to a lesser degree in barley and oats). Diagnosis is suspected on the basis of symptoms and signs, enhanced by laboratory and x ray studies, and confirmed by biopsy and response to a gluten free diet. Treatment for celiac disease involves complete avoidance of gluten in the diet. The author collected stories, recipes, information about books that have been useful, and general advice and offers them to the reader. The author reminds readers that celiac disease has a maze of symptoms and that every case seems to be different. The book demonstrates these differences with 20 compelling stories from people with celiac disease. The most common problems encountered are the lack of a timely diagnosis and a scarcity of information for the newly diagnosed people. The book concludes with a listing of vitamins and their biological function, a glossary of terms, and an order form with which to purchase additional copies of the book.
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Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment Source: Chicago, IL: Quintessence Publishing Co, Inc. 2003. 908 p.
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Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $399.00 plus shipping and handling. ISBN: 0867153903. Summary: This book is a clinically oriented guide for oral and maxillofacial surgeons and other advanced dental and medical specialists who deal with pathologies in the oral cavity, midface, and neck. The authors focus on the mechanisms of each disease and how that dictates its clinical and radiographic presentation as well as the considerations on a sample differential diagnosis. The book also includes specific treatment recommendations that the authors use or have researched as the most beneficial. The text includes nineteen chapters: biopsy principles and techniques; inflammatory, reactive, and infectious diseases; immune-based diseases; conditions of developmental disturbances; hyperplasias, hamartomas, and neoplasms; benign epithelial tumors of mucosa and skin; premalignant and malignant epithelial tumors of mucosa and skin; management of irradiated patients and osteoradionecrosis; benign soft tissue tumors of mesenchymal origin; malignant soft tissue tumors of mesenchymal origin; nonneoplastic salivary gland diseases; salivary gland neoplasms; odontogenic and nonodontogenic cysts; odontogenic tumors (hamartomas and neoplasms); pigmented lesions of mucosa and skin; fibro-osseous diseases and systemic diseases affecting bone; benign neoplasms of bone; malignant neoplasms of bone; and neoplasms of the immune system. The text concludes with a bibliography, glossary of terms, and detailed subject index. Extensive full-color photographs illustrate the volume. •
Challenges of Lupus: Insights and Hope Source: Garden City Park, NY: Avery Publishing Group. 1999. 255 p. Contact: Available from Penguin-Putnam, Inc. Consumer Sales, 405 Murray Hill Parkway, East Rutherford, NJ 07073. (800) 788-6262. PRICE: $14.95 plus shipping and handling. ISBN 0895298813. Summary: This book provides people who have lupus with information that will help them take better care of themselves by better understanding their disease. The book is a compilation of 40 articles written by experts on the subject of lupus. The book is organized into six parts. Part 1, which serves as an introduction to lupus, provides readers with an overview. Topics include the epidemiology, manifestations, diagnosis, etiology, and management of lupus. Part 2 recounts the author's personal experiences and the experiences of others with lupus. Part 3 discusses the way lupus affects different groups of people at different stages of life, including newborns, children, women, men, the elderly, and pregnant women. Part 4 explains the different manifestations of lupus, such its effects on the lungs, the skeletal system, the central nervous system, the heart and blood vessels, the blood, and the skin. Part 5 details the medications that are used in the treatment of lupus, including corticosteroids, nonsteroidal antiinflammatory drugs, antimalarial drugs, and cytotoxic drugs. Other topics include the development of drug induced lupus; the treatment of blood disorders, pain, and psychiatric, neurologic, cardiovascular, renal, cutaneous, and gastrointestinal manifestations; the psychiatric side effects of lupus medications; the use of placebos; and the role of a kidney biopsy. Part 6 examines the importance of the physician patient relationship. The book includes a glossary and a list of local chapters of the Lupus Foundation of America. 41 references.
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Prostate: Questions You Have, Answers You Need. Revised ed Source: Allentown, PA: People's Medical Society. 1996. 192 p.
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Contact: Available from Independent Publishers Group. Order Department, 814 N. Franklin Street, Chicago, IL 60610. (800) 888-4741 or (312) 337-0747. Fax (312) 337-5985. E-mail:
[email protected]. PRICE: $12.95. ISBN: 1882606639. Summary: This book provides readers with a consumer's guide to the prostate and to prostatic diseases. After an introductory chapter on the anatomy and physiology of the prostate, the author describes three types of prostatic disease: prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. The latter section covers stages of prostate cancer, diagnostic tests including rectal exams, the prostate-specific antigen (PSA) test, transrectal ultrasound, and biopsy and other staging tests, and prevention issues. The next chapter reviews the treatment options for BPH, including surgery, its mortality and complications, alternative procedures, medication, and self help. A final chapter describes treatment options for prostate cancer, including surgery, radiation therapy, hormonal therapy, drug therapy, other therapies, nontreatment, treatment according to stage, and followup and recurrence. The book concludes with a section on informational and mutual-aid groups, a glossary of related terms, a list of suggested readings, and a subject index. The book is written in a question and answer format, with nontechnical language used throughout. 7 references. •
Diagnosis and Treatment Source: in Scully, C. Handbook of Oral Disease: Diagnosis and Management. New York, NY: Thieme New York. 2001. p.385-406. Contact: Available from Thieme New York. 333 Seventh Avenue, New York, NY 10001. (212) 760-0888, ext 110. PRICE: $35.00 plus shipping and handling. ISBN: 1841840874. Summary: This chapter on diagnosis and treatment is the final chapter in a handbook of oral disease that is intended to be used by all members of the dental team who need a ready office reference. The handbook covers the more common and important soft tissue orofacial disorders and gives clinically relevant aspects of the etiology, diagnosis, treatment, and prevention. In this chapter, the authors review certain management procedures that are commonplace. The purpose of making a diagnosis is to be able to offer the most effective treatment, safest treatment, and most accurate prognosis. Diagnosis most importantly involves a careful history. Dental staff should inquire about extraoral lesions; observe the patient's affect, behavior, movements, and gait; and inspect and examine the hands, fingers, nails, wrists, face, and neck and cervical lymph nodes. A careful inspection and examination of the oral and perioral structures is mandatory. The authors also discuss diagnostic tests, biopsy, biopsy technique, histology, lymph nodes, the use of frozen sections for rapid diagnosis, and oral smears for cytology. Management issues discussed include oral hygiene, diet, treatment of oral lesions, analgesia (painkillers), immunosuppressive agents, retinoids, antimicrobials, antifungals, antivirals, antidepressants, and when to refer to a specialist. Much of the information is provided in table or outline format for ease of reference. Full color photographs illustrate some conditions. 4 figures. 11 tables. 57 references.
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Management of Hepatitis C: NIH Consensus Development Conference Program and Abstracts Source: Bethesda, MD: National Institutes of Health. 1997. 139 p. Contact: Available from NIH Consensus Program Information Center. P.O. Box 2577, Kensington, MD 20891. (888) 644-2667. Fax (301) 816-2494. PRICE: Single copy free.
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Summary: This document presents abstracts of the NIH Consensus Development Conference on the Management of Hepatitis C, held in March 1997 in Bethesda, Maryland. It notes the conference's agenda, panel, speakers, and planning committee members. The document was designed for the use of panelists and participants in the conference and as a pertinent reference document for anyone interested in the conference deliberations. The abstracts are presented in four sections: the natural history of hepatitis C, diagnostic considerations, the epidemiology and spread of hepatitis C, and therapeutic issues. Specific topics covered include the clinical spectrum of disease, blood donors with hepatitis C, hepatitis C and hepatocellular carcinoma (liver cancer), hepatitis C and alcohol, diagnostic tests for hepatitis C, the role of liver biopsy, the epidemiology of hepatitis C, the sexual and perinatal spread of hepatitis C virus infection, the use of interferon alfa-2b, ribavirin treatment, drug side effects, predictive factors for a beneficial response to drug therapy in hepatitis C, the treatment of patients with liver cirrhosis, retreatment with interferon, and cost effectiveness considerations. Each abstract includes brief references. •
Hepatitis C: Diagnostic Techniques and Monitoring Strategies Source: Thousand Oaks, CA: Amgen, Inc. 1997. 32 p. Contact: Available from Amgen Professional Services. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 77-AMGEN. PRICE: Single copy free to health professionals. Summary: This document summarizes the present diagnostic techniques and monitoring strategies used as part of the management of hepatitis C virus (HCV). HCV infection results in a chronic disease state in 50 to 70 percent of cases and is now the most common cause of chronic liver disease in the United States. It is highly infectious; known routes of transmission include blood and blood products, injection drug use, and sexual contacts. The virus has been cloned and is now well characterized with respect to both structural and nonstructural proteins. Molecular cloning technology has resulted in the development of specific and sensitive screening, diagnostic, and monitoring assays for HCV. In addition, tests to determine the quantity of viral RNA in blood and to define areas of the viral genome have been developed. Both viral load and genome have been suggested to be predictive of patient response to therapy. The authors review HCV diagnostic and monitoring tests, including liver enzymes, serological assays, virological assays, genotyping and serotyping, and liver biopsy. The discovery of antibodies to HCV or elevated ALT in a patient with or without symptoms of liver disease frequently culminates in the diagnosis of hepatitis C. The sequence of tests used to confirm the diagnosis may depend on the patient's known risk factors and the type of test (ALT, anti-HCV, or both) that initially established the likelihood of infection. The authors conclude that once the diagnosis of HCV infection is confirmed, determination of the presence or absence of cirrhosis, HCV RNA concentration, and genotype or serotype are important predictive factors in determining which patients are most likely to respond to therapy. 8 figures. 8 tables. 66 references. (AA-M).
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Gastrointestinal Diseases and Disorders Sourcebook Source: Detroit, MI: Omnigraphics, Inc. 1996. 413 p. Contact: Available from Omnigraphics, Inc. Penobscot Building, Detroit, MI 48226. (800) 234-1340 or (313) 961-1340. Fax (800) 875-1340 or (313) 961-1383. PRICE: $75.00. ISBN: 0780800788.
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Summary: This health reference book provides nontechnical information about gastrointestinal diseases and disorders. This sourcebook describes the signs and symptoms of many digestive system problems, discusses ongoing research and treatment, provides statistical data, and recommends dietary and lifestyle changes. The book has 46 chapters arranged in five sections: general information, including how the digestive system works, how to maintain healthy digestion, and statistical data; esophageal problems, including hiatal hernia, heartburn, and chronic pulmonary aspiration in children; stomach problems, notably ulcers and their treatment; intestinal and anorectal disorders; and liver, pancreatic, and gallbladder diseases and disorders, including liver function tests, liver transplants, and liver biopsy. The sourcebook includes numerous charts and graphs; a subject index concludes the volume. •
Glenn's Urologic Surgery. 5th ed Source: Philadelphia, PA: Lippincott Williams and Wilkins. 1998. 1149 p. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: This massive textbook on urologic surgery offers 137 chapters on every aspect of anesthesia, antibiosis, medical techniques, diagnostics, and the fundamental considerations and technical aspects of urologic surgery. The chapters are organized into 14 sections: adrenal, kidney, ureter and pelvis, bladder, prostate, urethra, vas deferens and seminal vesicle, testes, penis and scrotum, urinary diversion, pediatric urology, endoscopy, laparoscopy, and frontiers (future developments). Some specific topics covered are Cushing's disease, primary aldosteronism, nephrectomy (removal of the kidney), renovascular disease, renal trauma, kidney transplantation, ureteral reconstruction, cystectomy (bladder removal), bladder augmentation, fistula, interstitial cystitis, prostatectomy (removal of the prostate), prostatic ultrasound and needle biopsy, bladder neck suspension techniques, pelvic floor relaxation, cystocele, female urethral diverticula, vaginal hysterectomy, urethral stricture, vasectomy, simple orchiectomy (removal of the testes), scrotal trauma and reconstruction, Peyronie's disease, priapism, penile prosthesis, penile trauma, urinary diversion techniques, bladder replacement, congenital anomalies, patient selection, circumcision, cystoscopy, kidney stone treatment, urinary stone treatment, stents, and thermotherapy. Each chapter includes diagrams, tables, and a list of references. A detailed subject index concludes the textbook.
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Kidney Transplant Rejection: Diagnosis and Treatment. 2nd ed Source: New York, NY: Marcel Dekker, Inc. 1992. 773 p. Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (212) 696-9000. Fax (914) 796-1772. E-mail:
[email protected]. PRICE: $275.00. ISBN: 0824784871. Summary: This medical text on the diagnosis and treatment of kidney transplant rejection presents 26 chapters in 4 sections: the biology of the allograft response; the diagnosis of rejection; new immunosuppressive agents; and systemic problems with immunosuppression. Specific topics include the mechanisms of cell-mediated rejection; the role of cytokines; suppressor cell regulation; antibody-mediated rejection; the pathology of acute tubular necrosis and acute rejection; fine needle aspiration biopsy; monitoring the components of the immune system; radionuclides in the evaluation of kidney transplant rejection; magnetic resonance imaging; antilymphocyte antibody
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therapy; cyclosporine; nephrotoxicity; cytomegalovirus infection; cancer in recipients of organ allografts; HIV infection and kidney transplantation; and molecular biology of transplant rejection. Each chapter, written by international experts in the field, includes numerous charts and diagrams, as well as extensive references. A detailed subject index concludes the volume. •
Diseases of the Liver and Biliary System. 10th ed Source: Oxford, England: Blackwell Science. 1997. 714 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. PRICE: $150.00. ISBN: 0865429065. Summary: This medical textbook presents a comprehensive account of diseases of the liver and biliary system, designed to be of use to physicians, surgeons and pathologists, and also as a reference text for the clinical student. Chapters cover anatomy and function; assessment of liver function; needle biopsy of the liver; the hematology of liver disease; ultrasound, computed tomography, and magnetic resonance imaging; hepatocellular failure; hepatic encephalopathy; fulminant hepatic failure; ascites; the portal venous system and portal hypertension; the hepatic artery and hepatic veins, i.e., the liver in circulatory failure; jaundice; cholestasis; primary biliary cirrhosis; sclerosing cholangitis; virus hepatitis; chronic hepatitis; drugs and the liver; hepatic cirrhosis; alcohol and the liver; iron overload states; Wilson's disease; nutritional and metabolic liver disease; the liver in infancy and childhood; the liver in pregnancy; the liver in systemic disease and hepatic trauma; the liver in infections; hepatic tumors, including hepato-cellular carcinoma; imaging of the biliary tract, including interventional radiology and endoscopy; cysts and congenital biliary abnormalities; gallstones and inflammatory gallbladder diseases; benign stricture of the bile ducts; diseases of the ampulla of Vater and pancreas; tumors of the gallbladder and bile ducts; and hepatic transplantation. The volume includes full color photographs, extensive reference lists with each chapter, and a detailed subject index.
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Flexible Fiberoptic Sigmoidoscopy Source: Research Triangle Park, NC: Glaxo, Inc. 1992. 29 p. Contact: Available from Glaxo Video Library. 5 Moore Drive, Research Triangle Park, NC 27709. (800) 824-2896. PRICE: Single copy free; available to health care professionals only. Item Number GVL231 (monograph). Summary: This monograph is designed to educate physicians about the indications, contraindications, and proper technique for using flexible sigmoidoscopy to screen for colorectal cancer. Topics include screening techniques for colorectal cancer; the types of sigmoidoscopes; indications and contraindications for fibersigmoidoscopy; patient preparation; sigmoidoscopy technique; common pathology; endoscopic biopsy and polypectomy; the cleaning and care of the sigmoidoscopy; complications of fibersigmoidoscopy; training and credentials; and the cost-effectiveness of fibersigmoidoscopy surveillance. The author stresses that, as screening becomes more widespread, the changes of detecting cancer in asymptomatic patients will improve, as will the options for treatment and the patients' survival rate. The booklet includes materials, including a posttest, with which readers can obtain 1 hour of Continuing Medical Education, Category 1. The booklet features color photographs. 66 references. (AA-M).
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Evaluating and Managing Interstitial Cystitis Source: Englewood Cliffs, NJ: University Research Associates Rx, Inc. 1997. 47 p. Contact: Available from University Research Associates Rx, Inc. 560 Sylvan Avenue, Englewood Cliffs, NJ 07632. (201) 816-0110. PRICE: Contact distributor directly for current prices for professionals. Summary: This monograph reviews current concepts of the pathogenesis of interstitial cystitis (IC) as well as new methods to successfully diagnose and manage this disease. IC is characterized by severe urinary frequency, urgency, and lower abdominal or perineal pain in the absence of any bacterial infection or other definable pathology. IC also has mild and moderate states. IC typically has a gradual onset with an insidious progression. The author notes that it may be that IC encompasses a number of different etiologies, all involving a bladder insult that ultimately results in urinary frequency and urgency. An important purpose for using this broader definition of IC is that many patients with milder forms could readily benefit from therapy if the diagnosis is considered. One of the main diagnostic problems with IC is a lack of pathologic findings that are readily identified and quantified. Diagnostic procedures discussed include the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC, the use of a voiding log, the physical examination, urodynamics, the potassium test, cystoscopic inspection and hydrodistension, and biopsy. Treatment options covered include antidepressant therapy, hydrodistension of the bladder under anesthesia, dimethyl sulfoxide (DMSO) instillation, antihistamines, steroids, intravesical silver nitrate, sodium oxychlorosene, heparinoid therapy, pentosan polysulfate (Elmiron), and surgery. The author stresses that, when discussing therapy with the patient, it is important to emphasize that if symptoms have been present for more than a year, no particular therapy is likely to be curative. While the patient may have a significant remission of symptoms, in all probability relapse will occur. The author concludes that perhaps 75 to 85 percent of patients with moderate to severe IC can experience significant, indefinite remissions with conservative therapy and avoid the need for extirpative surgery. The monograph concludes with the package insert information for Elmiron. 3 figures. 6 tables. 105 references. (AA-M).
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Clinician's Guide to Treatment of Medically Compromised Dental Patients Source: Baltimore, NY: American Academy of Oral Medicine (AAOM). 1995. 82 p. Contact: Available from American Academy of Oral Medicine (AAOM). 2910 Lightfoot Drive, Baltimore, MD 21209-1452. (410) 602-8585. Website: www.aaom.com. PRICE: $21.00 plus shipping and handling. Summary: This monograph, a guide for dentists, is designed to aid in the anticipation, recognition, and management of problems of medically compromised dental patients. The clinician should be able to use this guide to review or become acquainted with the more common medically related disorders that present in the dental office, including: cardiovascular disease; cerebrovascular disease; craniofacial neurology; severe dermatologic disease; endocrine disorders, including diabetes; hematologic disease; hepatitis; neurological disorders; oral cancer; patients with prosthetic devices; pulmonary disease; and renal disease. For each topic, the authors note the definition, etiology, and clinical presentation, notably the oral and dental significance; much of the material is presented in outline or chart form for easy reference. An additional chapter discusses biopsy, cytology, and clinical laboratory procedures.
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Liver Disorders Sourcebook Source: Detroit, MI: Omnigraphics. 2000. 591 p. Contact: Available from Omnigraphics, Inc. 615 Griswold, Detroit, MI 48226. (800) 2341340. Fax (800) 875-1340. PRICE: $78.00 plus shipping and handling. ISBN: 0780802403. Summary: This Sourcebook provides basic health care information about liver functions, guidelines for liver health, and tests that assess liver distress. The book also presents the symptoms, treatments, and preventive measures available for liver cancer; hepatitis A, B, C, D and E; genetically based liver diseases; and other liver diseases. The liver transplantation process is explained. Specific topics include strategies for protecting the liver, risk factors, common laboratory tests in liver disease, liver biopsy, cancer tumor markers, cirrhosis (scarring of the liver), infectious agents and parasites, pregnancy and the liver, jaundice in the healthy newborn, the liver's response to drugs, alcohol and the liver, acetaminophen, herbs and alternative medicine, galactosemia, Gaucher disease, hereditary hemochromatosis, Niemann-Pick disease, Wilson's disease, biliary atresia, cystic disease of the liver, fatty liver, gallstones, primary biliary cirrhosis, primary sclerosing cholangitis, organ donation, and the bioartificial liver. A glossary, a directory of organizations and support groups with up to date contact information (including websites and email addresses), a listing of transplant centers, and a subject index conclude the volume.
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Atlas of Minor Oral Surgery Source: Philadelphia, PA: W.B. Saunders Company. 2001. 320 p. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $75.00 plus shipping and handling. ISBN: 0721679773. Summary: This text provides background information and guidelines for the oral surgical procedures that are an integral component of modern dentistry. The text covers surgical procedures commonly performed in an outpatient office setting with the use of local anesthesia. The text is divided into nine sections: basic principles, exodontia (the extraction of teeth), advanced procedures, infections, pathology, prosthetic surgery, implants, trauma, and salivary gland disease. Specific topics include medical evaluation of the patient, local anesthesia, oral and parenteral sedation, perioperative hemorrhage, impacted third molar teeth, endodontic (root canal) surgery, treatment of sinus infections, antibiotics, cysts, biopsy techniques, bone grafting for implants, the sinus lift procedure, evaluation and treatment planning for implants, evaluating dentoalveolar injuries, repair of lacerations, and management of commonly seen salivary gland diseases. The text is copiously illustrated with black and white line drawings. The text includes one appendix that offers four tables useful laboratory information and common drug interactions information; a subject index concludes the text.
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Atlas of Diseases of the Kidney. Volume 2: Glomerulonephritis and Vasculitis/Tubulointerstitial Disease Source: Philadelphia, PA: Current Medicine, Inc. 1999. [204 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]. PRICE: $75.00 plus shipping and handling. ISBN: 0632043873.
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Summary: This volume is one in a series of five in the Atlas of Diseases of the Kidney, a set that offers educational images including colored photographs, schematics, tables, and algorithms. In this volume, the first section covers glomerulonephritis and vasculitis; the second section covers tubulointerstitial disease. Twelve chapters cover normal vascular and glomerular anatomy; the primary glomerulopathies; heredofamilial and congenital glomerular disorders; infection associated glomerulopathies; vascular disorders; renal interstitium and major features of chronic tubulointerstitial nephritis; urinary tract infection; reflux and obstructive nephropathy; cystic diseases of the kidney; toxic nephropathies; metabolic causes of tubulointerstitial disease; and renal tubular disorders. Each chapter features a detailed introduction and lengthy captions for each of the illustrations and diagrams offered. The first section relies heavily on images provided by analysis of renal biopsy; the section on vascular diseases of the kidney emphasizes microscopic images that illustrate essential or characteristic features of disease. A subject index for Volume 2 and a section of full color plates concludes the book. •
Nephrology and Hypertension. 4th ed Source: Hagerstown, MD: Lippincott Williams and Wilkins. 1999. 368 p. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: www.lww.com. PRICE: $26.95 plus shipping and handling. ISBN: 078172077X. Summary: Written by those who remember the information that was useful to them in their training, this book provides students, residents, and practitioners with basic clinical information on commonly encountered conditions in nephrology (kidney disease). Chapter 1 provides a brief overview of the structural and functional features of the kidney. Chapters 2 through 4 outline a practical approach to the functional and radiologic evaluation of the kidney, including the clinical indications for a kidney biopsy. Chapter 5 discusses the clinical significance of hematuria (blood in the urine) and identifies those clinical settings in which thorough evaluation is a necessity. In Chapter 6, the etiology, pathophysiology, and method of evaluation of proteinuria (protein in the urine) and the nephrotic syndrome are presented. Chapter 7 reviews diabetic nephropathy; then Chapter 8 discusses several forms of renal disease that are glomerular in type, including minimal change disease, focal segmental glomerulosclerosis, membranous glomerulonephritis, post infectious proliferative glomerulonephritis, and IgA nephropathy. Chapter 9 describes the various types of glomerulonephritis observed in patients with systemic lupus erythematosus (SLE). In Chapter 10, the problem of vasculitis is addressed in its many forms, including Wegener's granulomatosis, polyarteritis nodosa, and Schonlein Henoch purpura. Chapter 11 provides descriptions of the renal (kidney) manifestations of the thrombotic microangiopathies, progressive systemic sclerosis, multiple myeloma, and amyloidosis. Chapter 12 discusses tubulointerstitial nephritis, and Chapter 13 reviews the more frequently encountered familial and cystic forms of renal disease. Chapter 14 covers HIV infection and the kidney, including management of HIV infected patients with acute or chronic renal failure. The next section contains four chapters on disorders of water, electrolytes, and acid base regulation. In Chapter 19 renal stone disease is reviewed; Chapter 20 covers urinary tract infection (UTI). The next five chapters cover the diagnosis and management of hypertension (high blood pressure) and the use of diuretics in clinical practice. The last section covers diagnosis and management of renal failure; six chapters cover dialysis, patient care management, the role of nutrition in managing kidney failure, and drug therapy for acute and chronic renal failure. Each
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chapter concludes with a list of suggested readings, and the handbook concludes with a subject index.
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 “biopsy” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “biopsy” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “biopsy” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Advances in Optical Biopsy and Optical Mammography by R. R. Alfano; ISBN: 1573311251; http://www.amazon.com/exec/obidos/ASIN/1573311251/icongroupinterna
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Aspiration biopsy for the community hospital by David B Kaminsky; ISBN: 089352154X; http://www.amazon.com/exec/obidos/ASIN/089352154X/icongroupinterna
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Atlas and Text of Aspiration Biopsy Cytology by Kenneth C. Suen; ISBN: 0683080245; http://www.amazon.com/exec/obidos/ASIN/0683080245/icongroupinterna
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Atlas of Biopsy Pathology for Heart and Lung Transplantation by Susan, Frcpath Stewart, et al; ISBN: 0340691425; http://www.amazon.com/exec/obidos/ASIN/0340691425/icongroupinterna
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Atlas of Colorectal Biopsy 1.0 (Pathology Atlas Series) by H. Appelman; ISBN: 0412089610; http://www.amazon.com/exec/obidos/ASIN/0412089610/icongroupinterna
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Atlas of laparoscopy and biopsy of the liver by Miquel Bruguera; ISBN: 0721621821; http://www.amazon.com/exec/obidos/ASIN/0721621821/icongroupinterna
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Bladder Biopsy Interpretation by Jonathan I., Md. Epstein, et al; ISBN: 0781742765; http://www.amazon.com/exec/obidos/ASIN/0781742765/icongroupinterna
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Bladder Biopsy Interpretation by Lucien E. Nochomovitz, et al; ISBN: 0881678783; http://www.amazon.com/exec/obidos/ASIN/0881678783/icongroupinterna
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Bladder Biopsy Interpretation by David G. Bostwick; ISBN: 1883477271; http://www.amazon.com/exec/obidos/ASIN/1883477271/icongroupinterna
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Bone Marrow Biopsies Revisited; ISBN: 3805535724; http://www.amazon.com/exec/obidos/ASIN/3805535724/icongroupinterna
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Bone Marrow Biopsies Updated: New Prospects for Clinical Diagnostics by B. Frisch, R. Bartl; ISBN: 3805538634; http://www.amazon.com/exec/obidos/ASIN/3805538634/icongroupinterna
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Color atlas of endoscopy and biopsy of the intestine; ISBN: 0721616097; http://www.amazon.com/exec/obidos/ASIN/0721616097/icongroupinterna
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Color Atlas of Nerve Biopsy Pathology by Shin J. Oh, Shin J., MD Oh; ISBN: 0849316766; http://www.amazon.com/exec/obidos/ASIN/0849316766/icongroupinterna
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Common Skin Biopsy Techniques Clinical Skills Teaching Module (Printed Material, PowerPoint Presenta by American College of Physicians; ISBN: 1930513240; http://www.amazon.com/exec/obidos/ASIN/1930513240/icongroupinterna
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Core Biopsy of the Breast by McCombs; ISBN: 1853172847; http://www.amazon.com/exec/obidos/ASIN/1853172847/icongroupinterna
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Cytological Aspiration Biopsy of the Thyroid Gland by Manfred Droese; ISBN: 0471565342; http://www.amazon.com/exec/obidos/ASIN/0471565342/icongroupinterna
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Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach by Michael T. Mazur, Robert J. Kurman; ISBN: 0387986154; http://www.amazon.com/exec/obidos/ASIN/0387986154/icongroupinterna
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Diagnostic Pathology of the Intestinal Mucosa: An Atlas and Review of Biopsy Interpretation by William O. Dobbins; ISBN: 0387970592; http://www.amazon.com/exec/obidos/ASIN/0387970592/icongroupinterna
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Encoscopic Biopsies of the Small Intestine and Colon by Kathryn Deschryver; ISBN: 080167042X; http://www.amazon.com/exec/obidos/ASIN/080167042X/icongroupinterna
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Endomyocardial Biopsy Interpretation by Margaret E. Billingham; ISBN: 0340563524; http://www.amazon.com/exec/obidos/ASIN/0340563524/icongroupinterna
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Endoscopy and Biopsy in Gastroenterology: Techniques and Indications by P. Fruhmorgen; ISBN: 0387096450; http://www.amazon.com/exec/obidos/ASIN/0387096450/icongroupinterna
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Endoscopy and Biopsy of Esophagus, Stomach and Duodenum: A Color Atlas by L. Demling; ISBN: 0721630235; http://www.amazon.com/exec/obidos/ASIN/0721630235/icongroupinterna
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Endoscopy and biopsy of the esophagus and stomach, by Konrad H Soergel; ISBN: 0721630138; http://www.amazon.com/exec/obidos/ASIN/0721630138/icongroupinterna
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Essentials of aspiration biopsy cytology by Gia-Khanh Nguyen; ISBN: 4260141880; http://www.amazon.com/exec/obidos/ASIN/4260141880/icongroupinterna
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Fine Needle Aspiration Biopsy of the Head and Neck by Celeste N. Powers, William J. Frable; ISBN: 075069503X; http://www.amazon.com/exec/obidos/ASIN/075069503X/icongroupinterna
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Fine Needle Aspiration Biopsy of the Liver by Martha Bishop Pitman, Wanda Maria Szyfelbein; ISBN: 0750694637; http://www.amazon.com/exec/obidos/ASIN/0750694637/icongroupinterna
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Fine Needle Aspiration Biopsy of the Pancreas by Barbara Centeno, Martha Bishop Pitman; ISBN: 0750697253; http://www.amazon.com/exec/obidos/ASIN/0750697253/icongroupinterna
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Fine Needle Aspiration Biopsy of the Rat Liver: Cytological, Cytochemical, and Biochemical Methods. Ed by G. Zbinden. Proc of Workshop, Zurich, May 19 by Workshop on Technique & Application of Fine Needle Aspiration Biopsy; ISBN:
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0080255086; http://www.amazon.com/exec/obidos/ASIN/0080255086/icongroupinterna •
GRASES COLOUR ATLAS OF LIVER BIOPSY - A CLINICAL PATHOLOGICAL GUIDE by PJ GRASES; ISBN: 0471564095; http://www.amazon.com/exec/obidos/ASIN/0471564095/icongroupinterna
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Handbook of fine needle aspiration biopsy cytology by Tilde S Kline; ISBN: 080162701X; http://www.amazon.com/exec/obidos/ASIN/080162701X/icongroupinterna
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Handbook of Renal Biopsy Pathology by Alexander J. Howie; ISBN: 0792368975; http://www.amazon.com/exec/obidos/ASIN/0792368975/icongroupinterna
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Handbook of Transrectal Ultrasound and Biopsy of the Prostate by Patel, David Rickards; ISBN: 1841841927; http://www.amazon.com/exec/obidos/ASIN/1841841927/icongroupinterna
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Image Guided Core Biopsy of the Breast: A Practical Approach by Chris Flowers; ISBN: 1900151480; http://www.amazon.com/exec/obidos/ASIN/1900151480/icongroupinterna
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Interpretation of biopsy of endometrium by Ancel U Blaustein; ISBN: 0890043701; http://www.amazon.com/exec/obidos/ASIN/0890043701/icongroupinterna
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Interpretation of Breast Biopsies (Book with CD-ROM) by Darryl Carter; ISBN: 0781733200; http://www.amazon.com/exec/obidos/ASIN/0781733200/icongroupinterna
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Interpretation of Endometrial Biopsies and Curettings by Richard J. Zaino; ISBN: 039751669X; http://www.amazon.com/exec/obidos/ASIN/039751669X/icongroupinterna
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Introduction to Biopsy Interpretation and Surgical Pathology by J. C. E. Underwood; ISBN: 0387104348; http://www.amazon.com/exec/obidos/ASIN/0387104348/icongroupinterna
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Kidney biopsy (SuDoc HE 20.3323/3:K 54) by U.S. Dept of Health and Human Services; ISBN: B000114U2C; http://www.amazon.com/exec/obidos/ASIN/B000114U2C/icongroupinterna
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Kidney Biopsy Interpretation by Edwin H. Jenis; ISBN: 0803649908; http://www.amazon.com/exec/obidos/ASIN/0803649908/icongroupinterna
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Liver biopsy (SuDoc HE 20.3302:L 75) by U.S. Dept of Health and Human Services; ISBN: B000112XVW; http://www.amazon.com/exec/obidos/ASIN/B000112XVW/icongroupinterna
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Liver Biopsy Diagnoses and Reports: Snomed Codes, Icd-9-Cm Codes, Nomenclature, and Terminology by Jurgen Ludwig; ISBN: 3805538413; http://www.amazon.com/exec/obidos/ASIN/3805538413/icongroupinterna
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Liver Biopsy Evaluation: Histologic Diagnoses with Clinical by Gary C. Kanel, Jacob, MD Korula; ISBN: 0721676928; http://www.amazon.com/exec/obidos/ASIN/0721676928/icongroupinterna
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Liver Biopsy Interpretation by Peter J. Scheuer, Jay H. Lefkowitch; ISBN: 070202502X; http://www.amazon.com/exec/obidos/ASIN/070202502X/icongroupinterna
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Lung Biopsy Interpretation by Eugene J. Mark; ISBN: 0683055925; http://www.amazon.com/exec/obidos/ASIN/0683055925/icongroupinterna
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Lymph Node Biopsy Interpretation by A.G. Stansfeld, A.J. D'Ardenne; ISBN: 0443040729; http://www.amazon.com/exec/obidos/ASIN/0443040729/icongroupinterna
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Modified fine-needle aspiration biopsy of the kidney on the study of glomerular pathology by Heikki Helin; ISBN: 9514409159; http://www.amazon.com/exec/obidos/ASIN/9514409159/icongroupinterna
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Mucosal Biopsy of the Gastrointestinal Tract by Richard Whitehead; ISBN: 0721632874; http://www.amazon.com/exec/obidos/ASIN/0721632874/icongroupinterna
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Muscle Biopsy Techniques by Loughlin; ISBN: 0407007733; http://www.amazon.com/exec/obidos/ASIN/0407007733/icongroupinterna
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Needle Biopsy of the Thyroid by J. Martin Miller, et al; ISBN: 0275914038; http://www.amazon.com/exec/obidos/ASIN/0275914038/icongroupinterna
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Optical Biopsies and Microscopic Techniques III by Irving J. Bigio, et al; ISBN: 0819430307; http://www.amazon.com/exec/obidos/ASIN/0819430307/icongroupinterna
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Optical Biopsy and Fluorescence Spectroscopy and Imaging by Rinaldo Cubeddu, Renato Marchesini; ISBN: 0819416576; http://www.amazon.com/exec/obidos/ASIN/0819416576/icongroupinterna
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Optical biopsy and tissue optics: 5-6 July 2000, Amsterdam, Netherlands; ISBN: 0819438170; http://www.amazon.com/exec/obidos/ASIN/0819438170/icongroupinterna
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Optical Biopsy III: 23-24 January 2000, San Jose, California by R. R. Alfano, et al; ISBN: 0819435333; http://www.amazon.com/exec/obidos/ASIN/0819435333/icongroupinterna
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Optical Biopsy IV by Robert R. Alfano; ISBN: 0819443522; http://www.amazon.com/exec/obidos/ASIN/0819443522/icongroupinterna
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Pathology: The Mammographically Directed Biopsy (State of the Art Reviews, Volume 1 / Number 1) by James L. Bennington (Editor), Michael D. Lagios (Editor); ISBN: 1560530790; http://www.amazon.com/exec/obidos/ASIN/1560530790/icongroupinterna
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Positioning Biopsy Needles in the Prostate Gland Using 3d Computer Modelling by Hans Frimmel; ISBN: 9155445160; http://www.amazon.com/exec/obidos/ASIN/9155445160/icongroupinterna
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Practical Liver Biopsy Interpretation: Diagnostic Algorithms by Jurgen, M.D. Ludwig; ISBN: 0891893474; http://www.amazon.com/exec/obidos/ASIN/0891893474/icongroupinterna
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Proceedings of Optical Biopsies and Microscopic Techniques: 7-9 September 1996, Vienna, Austria by Irving J. Bigio (Other Contributor); ISBN: 0819423289; http://www.amazon.com/exec/obidos/ASIN/0819423289/icongroupinterna
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Proceedings of Optical Biopsy 4-5 September 1993 Budapest, Hungary by Rinaldo Cubeddu; ISBN: 0819413488; http://www.amazon.com/exec/obidos/ASIN/0819413488/icongroupinterna
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Prostate Biopsy Interpretation (Book with CD-ROM) by Jonathan I. Epstein, Ximing J. Yang; ISBN: 0781732875; http://www.amazon.com/exec/obidos/ASIN/0781732875/icongroupinterna
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Renal Biopsy Interpretation by Fred G., MD Silva, et al; ISBN: 0443077843; http://www.amazon.com/exec/obidos/ASIN/0443077843/icongroupinterna
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Renal biopsy pathology, with diagnostic and therapeutic implications by Benjamin H Spargo; ISBN: 0471031194; http://www.amazon.com/exec/obidos/ASIN/0471031194/icongroupinterna
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Stereotactic Biopsy and Brachytherapy of Brain Tumors by Peter Dyck; ISBN: 0839119267; http://www.amazon.com/exec/obidos/ASIN/0839119267/icongroupinterna
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Surgical pathology of bone marrow: Core biopsy diagnosis by Benjamin Wittels; ISBN: 0721614345; http://www.amazon.com/exec/obidos/ASIN/0721614345/icongroupinterna
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The Thyroid: Fine-Needle Biopsy and Cytological Diagnosis of Thyroid Lesions by Svante R. Orell, et al; ISBN: 3805563833; http://www.amazon.com/exec/obidos/ASIN/3805563833/icongroupinterna
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Ultrasound Guided Biopsy and Drainage by Rainer C. Otto, Josef Wellauer; ISBN: 3540162410; http://www.amazon.com/exec/obidos/ASIN/3540162410/icongroupinterna
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Using Skin Biopsy in the Office (Video with Common Skin Biopsy Techniques Video) by American College of Physicians; ISBN: 1930513194; http://www.amazon.com/exec/obidos/ASIN/1930513194/icongroupinterna
Chapters on Biopsy In order to find chapters that specifically relate to biopsy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and biopsy 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 “biopsy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on biopsy: •
When You Have Hepatitis B: Understanding the Diagnosis: Blood Tests and Biopsies Source: in Everson, G.T.; Weinberg, H. Living with Hepatitis B: A Survivor's Guide. Long Island, NY: Hatherleigh Press. 2002. p.18-37. Contact: Available from Hatherleigh Press. 5-22 46th Avenue Suite 200, Long Island City, NY 11101. (800) 528-2550. E-mail:
[email protected]. Website: http://store.yahoo.com/hatherleighpress/index.html. PRICE: $15.95 plus shipping and handling. ISBN: 1578260841. Summary: Chronic hepatitis B can lead to cirrhosis (liver scarring), liver cancer, and the need for liver transplantation. This chapter on diagnostic tests is from a book that helps readers diagnosed with hepatitis B virus (HBV) infection educate themselves about the disease and its treatment. The authors answer questions about the testing process for hepatitis B, from diagnosis through monitoring during the years of ongoing care. The chapter covers hepatitis B virus tests, including proteins, antigens, and antibodies; liver imaging tests, including ultrasound, computed tomography, and magnetic resonance
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imaging (MRI); liver biopsy, including the procedure used and how to interpret the results obtained; liver blood tests, including liver enzymes, bilirubin, albumin, clotting factors, alpha-fetoprotein, and complete blood count (CBC); and patterns of hepatitis B tests in patients, including for acute and chronic disease, and for chronic carriers. Throughout the chapter the authors include quotes from real people who are living with hepatitis. 6 figures. 3 tables. •
When You Have Hepatitis C, Understanding the Diagnosis: Blood Tests and Biopsies Source: in Everson, G.T. and Weinberg, H. Living with Hepatitis C: A Survivor's Guide. New York, NY: Hatherleigh Press. 1999. p. 15-30. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. PRICE: $14.95 plus shipping and handling. ISBN: 1578260345. Summary: Hepatitis C is a viral infection that causes inflammation, injury, and ultimately scarring of the liver (cirrhosis). This chapter discussing the diagnosis of hepatitis C is from a book that offers information and guidance for people living with hepatitis C. The authors explain in nontechnical language some basic facts about the testing process for hepatitis C from diagnosis through the years of ongoing care. Diagnostic tests described include: ELISA I, ELISA II, and III; RIBA; HCV RNA assays; PCR quantitative assay; branched chain DNA assay; genotyping and quasispecies; radiologic imaging; ultrasound; CT scan; and liver biopsy. The authors also discuss testing limits, interpreting biopsy results, and monitoring tests, including liver enzymes, bilirubin, albumin, clotting factors, and complete blood count (CBC). The authors note that one predictor of response to therapy may be the number of quasispecies of hepatitis C circulating in the patient's blood. The virus mutates freely, so patients often have multiple copies of the hepatitis C virus that vary genetically; these are called quasispecies. In addition, the subtypes of hepatitis C respond differently to therapy, so it can be useful to have the subtype diagnosed. The authors recognize that many readers fear even the word 'biopsy,' but they stress that only a biopsy can give the doctor a true idea of the condition of the liver. They detail exactly what the patient can expect during and after the biopsy. The chapter includes lengthy quotes from patients with hepatitis, which offer the patients' perspectives, insights, and experiences to the reader. 2 figures. 1 table.
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Renal Biopsy Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 63-69. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail:
[email protected] Website: www.elsevierhealth.com. PRICE: $199.00. ISBN: 723432589. Summary: The introduction of renal (kidney) biopsy transformed the study of renal disease, particularly glomerular disease, by providing the pathological information that formed the basis for a classification of disease still in current use and by offering many insights into pathogenesis (disease development). This chapter on renal biopsy is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The author of this chapter notes that the development of renal biopsy as a safe and informative technique was a key step in the evolution of nephrology as a specialty. Topics include the indications for renal biopsy, including
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nephrotic syndrome, acute renal failure, renal disease in the setting of a systemic disorder, and kidney transplant; preparation for renal biopsy; the procedure itself; modifications of the biopsy procedure; complications, including pain, hemorrhage, arteriovenous fistula; the diagnostic range of biopsy findings; and the value of renal biopsy, including issues of biopsy adequacy and biopsy interpretation. The chapter is clinically focused and extensively illustrated in full color. 6 figures. 3 tables. 20 references. •
Fine Needle Aspiration Biopsy in Clinical Renal Transplantation Source: in Andreucci, V.E. International Yearbook of Nephrology 1990. Hingham, MA: Kluwer Academic Publishers. 1990. p. 249-262. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA02018-0358. (617) 871-6600. Summary: This chapter discusses the technical, cytological, clinical, and investigational aspects of fine needle aspiration biopsy (FNAB) as a clinical and investigational tool in kidney transplantation. Attention is given to: application of the FNAB technique (clinical and cytological procedures and measurements of species); interpretation of FNAB results; and comparison of FNAB with core biopsy methodology. Activities of the use of FNAB as a clinical and a research tool are included. 43 references.
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Biopsy Principles and Techniques Source: in Marx, R.E.; Stern, D. Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment. Chicago, IL: Quintessence Publishing Co, Inc. 2003. p.1-15. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $ 399.00 plus shipping and handling. ISBN: 0867153903. Summary: This chapter on biopsy principles and techniques is from a clinically oriented guide for oral and maxillofacial surgeons and other advanced dental and medical specialists who deal with pathologies in the oral cavity, midface, and neck. The authors note that despite the sophisticated imaging techniques, precise blood studies, and nuclear scans available today, the scalpel blade and light microscope remain the most diagnostic tools. Tissue specimens determine the majority of diagnoses made by oral and maxillofacial surgeons and other practitioners. The challenge for the clinician is to provide a representative tissue specimen that is adequate in quantity, properly fixed, and without artifacts or distortion. Topics include brush biopsy as a screening tool for oral cancer, incisional versus excisional biopsy, principles of frozen section specimens, processing of biopsy specimens, approach to histologic interpretation, immunofluorescence testing, erythroleukoplakia of oral mucosa, ulcerative lesions of oral mucosa, immune-based vesicles and ulcers, radiolucent lesions in bone, radiopaque lesions in bone, biopsy of a mass at the junction of the hard and soft palate mucosa, nodules in the lip or cheek, lesions of the lower lip vermilion, and cervical lymph node biopsies. Full-color photographs illustrate the chapter. 23 figures.
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Principles of Differential Diagnosis and Biopsy Source: in Peterson, L.J., et al., eds. Contemporary Oral and Maxillofacial Surgery. 3rd ed. St. Louis, MO: Mosby-Year Book, Inc. 1998. p. 512-532.
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Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. PRICE: $69.00. ISBN: 0815166990. Summary: This chapter, from a textbook that provides a comprehensive description of the basic oral surgery procedures that the general practitioner performs in his or her office, discusses the principles of differential diagnosis and biopsy in oral pathology. The section on examination and diagnostic methods covers health history, history of the lesion, clinical examination, radiographic examination, laboratory investigation, and surgical specimens for pathologic examination. The section on the principles of biopsy covers oral cytology, aspiration biopsy, incisional biopsy, and excisional biopsy. The next section covers soft tissue biopsy techniques and surgical principles, including anesthesia, tissue stabilization, hemostasis, incision, handling of tissue, identification of surgical margins, specimen care, surgical closure, and the biopsy data sheet. Another section discusses intraosseous (hard tissue) biopsy techniques and surgical principles, including aspiration biopsy of radiolucent lesions, mucoperiosteal flaps, osseous window, removal of specimen, and specimen care. The chapter concludes with a section on referrals for biopsy, in which the author discusses factors including the health of the patient, surgical difficulty, and the potential for malignancy. The chapter is illustrated with black and white photographs, drawings, and radiographs. 14 figures. 1 table. •
Biopsies: Checking for Cancer: Digestive System Source: in Shaw, M., et al., eds. Everything You Need to Know About Medical Tests. Springhouse, PA: Springhouse Corporation. 1996. p. 222-225. Contact: Available from Springhouse Publishing. Attention: Trade and Textbook Department, 1111 Bethlehem Pike, P.O. Box 908, Springhouse, PA 19477-0908. (800) 3313170 or (215) 646-4670 or (215) 646-4671. Fax (215) 646-8716. PRICE: $24.95 (as of 1995). ISBN: 0874348234. Summary: This section on the digestive system, from a chapter on biopsy, is from a consumer reference guide to over 400 diagnostic tests. For each test, the book covers the reasons the test is performed; what patients should know before the test; what to expect during and after the test; risk factors associated with the test; the normal results; and what abnormal results mean. Tests in this section include small intestine biopsy and liver biopsy.
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CHAPTER 7. MULTIMEDIA ON BIOPSY Overview In this chapter, we show you how to keep current on multimedia sources of information on biopsy. 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 biopsy is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “biopsy” 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 “biopsy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on biopsy: •
When Milk Doesn't Do a Body Good Source: Madison, WI: University of Wisconsin Hospitals and Clinics, Department of Outreach Education. 1996. (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 032096A. Summary: Lactose, the sugar component of milk, is made of glucose and galactose. The intestine cannot digest complex sugar, so the body needs the enzyme lactase to break lactose into these simpler sugars. Without adequate lactase levels, symptoms of lactose intolerance can become problematic. 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 gastroenterologist Mark Lloyd, the common symptoms, diagnosis, and management of lactose intolerance
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are covered. Dr. Lloyd explains why some people cannot digest milk, defines lactose intolerance, notes who is most affected, and reviews treatment options. Rarely, an infant is born with no lactase; these few children become sick early in life and are usually diagnosed quickly. However, most humans (and other mammals) have no problems with milk in the early years. About 75 percent of the world's population has some problems with lactose; levels vary by ethnic group. The symptoms of lactose intolerance include stomach rumbling and bloating, gas (flatulence), and diarrhea. Dr. Lloyd reviews the differences between lactose intolerance and milk allergy, which is an immunologic reaction. The program then focuses on the diagnosis and management of lactose intolerance. Lactose withdrawal (removing milk and milk products from the diet) or lactose tolerance testing (blood sugar tests and breath hydrogen tests) are used for diagnosis; sometimes biopsy is indicated. The program lists foods high in lactose and offers readers suggestions for dietary modification and the use of lactase supplements. The program concludes by referring viewers to the National Digestive Diseases Information Clearinghouse (NDDIC). •
Helicobacter Pylori in Peptic Ulcer Disease Source: Secaucus, NJ: Network for Continuing Medical Education. 1994. (videocassette). Contact: Available from Network for Continuing Medical Education. 1425 Broad Street, Clifton, NJ 07013. (800) 223-0272 or (973) 473-9500. Fax (973) 591-1224. Order Number: 671. PRICE: Call for pricing information. Summary: Peptic ulcer disease is a chronic inflammatory condition of the stomach and duodenum that affects as many as 10 percent of Americans at some time in their lives. This medical continuing education program reviews the role of H. pylori in peptic ulcer disease. The program describes the pathogenesis of H. pylori infection, progression of disease, epidemiology, related nomenclature, transmission, invasive (endoscopy, gastric biopsy) and noninvasive (serology, urease breath test) diagnostic tests used to confirm H. pylori infection, patient selection, treatment regimens, and factors that affect healing. The program emphasizes that all patients who have PUD and test positive for H. pylori should be treated with an antibiotic regimen; patients who are H. pylori positive but are asymptomatic should not be treated prophylactically. The video features live action of real physicians and patients, and graphics and anatomic illustrations.
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Oral Cancer Screening: A Brief Review Source: Pittsburgh, PA: Oral Cancer Center, University of Pittsburgh. 2002. (video). Contact: Available from University of Pittsburgh Oral Cancer Center. (412) 648-8513. Email:
[email protected]. Website: www.upci.upmc.edu/internet/occ/. PRICE: Available for free on the Web. Contact for availability of VHS copies. Summary: The head and neck cancer exam is a brief procedure that can be routinely performed by all health care providers. It requires no special equipment and is considered non-invasive. This procedure may discover cancer in an early stage and can help patients avoid major potentially-disfiguring surgery. In this video, health professionals can quickly review how to conduct the examination of the oral cavity and the head and neck. Narrated by Dr. Nancy Snyderman, the video includes an interview with a patient who had tongue cancer that was not identified early in its development. The program briefly reviews the risk factors for oral cancer, including male gender, age older than 50 years, tobacco use (including smokeless tobacco), and alcohol use. The program then demonstrates the oral cavity exam, describes what the examiner should
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look for, and shows examples of significant lesions. The program concludes with a section demonstrating the use of the brush biopsy technique. •
Preparing for a Lower GI Endoscopy: A Patient's Perspective Source: Research Triangle Park, NC: Glaxo. 1994. Contact: Available from Glaxo. Educational Resource Center, Five Moore Drive, Research Triangle Park, NC 27709. (800) 334-0032 or (919) 248-2100. PRICE: Single copy free. Available to health professionals only. Summary: This patient education videotape provides information for the person about to undergo a lower gastrointestinal (GI) endoscopic procedure (colonoscopy). After brief definitions of colonoscopy and the role of the gastroenterologist, the video addresses the anatomy and physiology of the large intestine; earlier diagnostic tests including barium enema and x-rays; a description of the colonoscope; indications for colonoscopy, including blood loss, chronic diarrhea, treating active bleeding, screening for cancer, and removing colonic polyps; preoperative considerations, including preparing the colon, the patient consent form, a review of the procedure, and the IV prep, including sedative; the procedure itself, including biopsy; postoperative considerations, including the recovery room and instructions for home; and complications of the procedure. The videotape includes footage of the procedure itself, depictions of the doctor and patient, anatomical drawings, and photographs.
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Rational Approach to the Diagnosis, Treatment and Management of Interstitial Cystitis Source: Rockville, MD: Interstitial Cystitis Association. 1994. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail:
[email protected]. Website: www.ichelp.org. PRICE: $14.50 (as of 1995). Summary: This professional education videotape provides clinicians with an overview of the diagnosis, treatment, and management of interstitial cystitis (IC). Narrated by Dr. Phillip Hanno, the program defines IC; describes the symptoms and the chronic nature of the disease; discusses the exclusionary diseases to consider in the diagnosis of IC; demonstrates the urodynamic workup of a suspected IC patient, including the role of cystoscopy, bladder distension, and biopsy; details the treatment options for IC, including hydrodistension, DMSO therapy, oxychlorosene sodium (Chlorpactin) therapy, the use of tricyclic antidepressants, the use of sodium pentosanpolysulfate (Elmiron-includes availability of this not-yet-approved drug) transcutaneous electrical nerve stimulation (TENS), narcotics, fulgeration, and surgery; and outlines self-care strategies including acid restriction and urine alkalization, exercise, stress reduction, acupressure, biofeedback, products and supplies, bladder holding protocol, and patient education and support. The program concludes with a brief discussion of the role of the Interstitial Cystitis Association (ICA) in research and patient education and support.
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Basics of Alpha 1-Antitrypsin Liver Disease Source: Washington, DC: Alpha-1 Association. 200x. (videorecording). Contact: Available from Alpha-1 Association. 1225 Eye Street NW, Suite 1225, Washington, DC 20005-5918. (800) 521-3025 or (202) 887-1900. Fax: (202) 887-1964. Website: www.alpha1.org. E-mail:
[email protected]. PRICE: Contact organization for copies.
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Summary: This videocassette depicts a slide lecture program given by Dr. Jeffrey Teckman at an Alpha-1 Association conference. Dr. Teckman describes the physiology and chemistry of the alpha-antitrypsin system, then the pathophysiology of alpha1antitrypsin deficiency. Dr. Teckman uses highly technical language, but then defines his terms and uses graphics to explain how the pathophysiology works (not all slides to which he refers are included in this videotape). Dr. Teckman also discusses the complications that are seen with this common, but underdiagnosed, genetic liver disease, including chronic hepatitis (liver inflammation), cirrhosis (scarring of the liver), liver cancer, and emphysema. Other topics include the Swedish research study that provided a great deal of basic information about this disease, the genetics, screening, diagnosis, the role of liver biopsy in diagnosis, and treatment options. The program concludes with a section of questions from the lecture audience, along with Dr. Teckman's answers. •
Pediatric Urology: Cryptorchidism Source: Bellaire, TX: American Urological Association (AUA) Office of Education. 1990. (videocassette). Contact: Available from Karol Media. 350 North Pennsylvania Avenue, P.O. Box 7600, Wilkes-Barre, PA 18773-7600. (800) 608-0096. Fax (717) 822-8226. PRICE: $20.00. Item number 919-2071. Summary: This videocassette program, one of a series from the American Urological Association, presents interviews with six urologists discussing various topics in pediatric urology related to cryptorchidism. Topics include the optimal age for treatment; excerpts from the 'Koop Orchiopexy' procedure; retractile testes; hormones in the management of cryptorchidism; non-palpable testes; and cryptorchidism in the older patient, including malignancy, testis biopsy, and patient follow-up.
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Of Critical Importance: AIDS Precautions in Radiology Source: Urbana, IL: Carle Medical Communications. 199x. Contact: Available from Carle Medical Communications. 611 West Park Street, Urbana, IL 61801. (217) 384-4838. PRICE: $295, purchase; Rental: $65 for 3 days; $100 for 5 days. Summary: This videotape is designed to help radiologists and staff in radiology departments minimize the risk associated with care of patients with AIDS by identifying and reinforcing the use of universal precautions as outlined by the Centers for Disease Control. The video highlights the effective use of gowns, masks, gloves, and goggles during the following procedures: angiograms, insertion of contrast during uroradiology, insertion of barium enema catheters, percutaneous biopsy during CAT scans, and ultrasound-guided thoracentesis. The video also discusses necessary precautions to avoid needlesticks and cuts and demonstrates proper cleaning and sterilization techniques for instruments and surfaces that come into contact with potentially infected blood or body fluids. (AA-M).
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CHAPTER 8. PERIODICALS AND NEWS ON BIOPSY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover biopsy.
News Services and Press Releases One of the simplest ways of tracking press releases on biopsy 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 “biopsy” (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 biopsy. 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 “biopsy” (or synonyms). The following was recently listed in this archive for biopsy: •
Endobronchial biopsy does not discriminate COPD from asthma Source: Reuters Medical News Date: June 04, 2004
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Transjugular approach shows promise for kidney biopsy in high-risk patients Source: Reuters Medical News Date: April 09, 2004
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Novel prostate cancer marker spots cancer when the biopsy is negative Source: Reuters Medical News Date: April 09, 2004
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Rectal sensation test helps make prostate biopsy less painful Source: Reuters Medical News Date: December 29, 2003
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Europe drops liver biopsy for Schering-Plough's PegIntron Source: Reuters Industry Breifing Date: October 21, 2003
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Positive biopsy rate from prostate's affected side predicts cancer recurrence Source: Reuters Medical News Date: October 20, 2003
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Sentinel node biopsy already standard of care in breast cancer, despite lack of evidence Source: Reuters Medical News Date: October 14, 2003
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Sentinel-node biopsy effective in screening for breast cancer metastasis Source: Reuters Medical News Date: August 06, 2003
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Stereotactic core needle biopsy often misdiagnoses atypical ductal hyperplasia Source: Reuters Medical News Date: July 11, 2003
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Sentinel node biopsy indicated for thin melanomas of Clark level III or greater Source: Reuters Medical News Date: May 30, 2003
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SLN biopsy in node-negative women not associated with axillary relapse Source: Reuters Medical News Date: May 12, 2003 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.
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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 “biopsy” (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 “biopsy” (or synonyms). If you know the name of a company that is relevant to biopsy, 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 “biopsy” (or synonyms).
Newsletters on Biopsy Find newsletters on biopsy using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “biopsy.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “biopsy” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Myopathic Diseases Source: Bulletin on the Rheumatic Diseases. 51(3): 1-4. 2002. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on myopathic diseases. Various diseases and conditions affect skeletal muscle and result in symptoms, including weakness, fatigue, and muscle cramping. Myopathies can be classified as idiopathic inflammatory myopathies (IIMs) and metabolic myopathies. IIMs are a heterogeneous group of disorders characterized by symmetric proximal muscle weakness and elevated serum levels of enzymes derived from skeletal muscle. IIMs
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include polymyositis and dermatomyositis in adults, juvenile dermatomyositis, IIM with an associated malignancy, and inclusion body myositis. Metabolic myopathies are the result of known biochemical defects that alter the ability of muscle to maintain adequate levels of adenosine triphosphate. Eleven different diseases caused by an underlying defect in glycogen synthesis, glycogenolysis, or glycolysis have been identified, including McArdle's disease, phosphofructokinase deficiency, and acid maltase deficiency. Various disorders of fatty acid and mitochondrial metabolism can cause myopathy. Other causes of myopathic symptoms include neuropathic infectious agents, neoplasms, and certain drugs. Tests may be needed to diagnose a patient with myopathic symptoms. Tests that measure serum levels of creatine phosphokinase, aldolase, SGOT, SGPT, and LDH may be useful. Electromyography can be used to determine the classification, distribution, and severity of diseases affecting skeletal muscle. Other useful tests include forearm ischemic exercise testing, imaging techniques, and muscle biopsy. Treatment of a myopathic process is dependent on the diagnosis. Glucocorticoids are the standard treatment for the inflammatory myopathies. Other drugs that may be used include methotrexate, azathioprine, cyclosporine, cyclophosphamide, and cholorambucil. 1 table and 16 references.
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “biopsy” (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 biopsy: •
Salivary Gland Biopsy for Sjogren's Syndrome Source: Moisture Seekers Newsletter. 17(7): 1-3. October 1999. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda, MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. Summary: This article from a newsletter for people with Sjogren's syndrome (SS) describes the use of salivary gland biopsy for diagnostic purposes. The author notes that the salivary gland biopsy demonstrates the extent of salivary gland involvement, the extent of cellular infiltration, and how much normal tissue remains in the gland of the patient with SS. Many conditions, therapies, and medications can cause dry mouth (xerostomia) and decreased salivary function. The most definitive way of attributing the changes that take place in SS is to examine a sample of the salivary tissue microscopically (with a biopsy). The author reviews the three types of salivary glands (parotid, submandibular, and sublingual), characteristic changes in SS, classification and grading systems for describing salivary gland changes, what to expect during the biopsy procedure itself, and the role of other diagnostic methods in SS. The author stresses the importance of salivary gland biopsy, noting that a biopsy cannot be considered optional in the case of an individual with chronically enlarged salivary glands because of the risk of lymphoma.
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Academic Periodicals covering Biopsy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to biopsy. In addition to these sources, you can search for articles covering biopsy 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 9. 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 biopsy. 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 biopsy. 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 biopsy: Tamoxifen •
Systemic - U.S. Brands: Nolvadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202545.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. 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 Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 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:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
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). 12 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
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “biopsy” (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 1301578 1137 1331 1331 921 1306298
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “biopsy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
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 Biologists18 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.19 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.20 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/.
18 Adapted 19
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. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on biopsy 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 biopsy. 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 biopsy. 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 “biopsy”:
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Bone Cancer http://www.nlm.nih.gov/medlineplus/bonecancer.html Breast Cancer http://www.nlm.nih.gov/medlineplus/breastcancer.html Breast Diseases http://www.nlm.nih.gov/medlineplus/breastdiseases.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Liver Cancer http://www.nlm.nih.gov/medlineplus/livercancer.html Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.html Muscle Disorders http://www.nlm.nih.gov/medlineplus/muscledisorders.html Soft Tissue Sarcoma http://www.nlm.nih.gov/medlineplus/softtissuesarcoma.html Uterine Cancer http://www.nlm.nih.gov/medlineplus/uterinecancer.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 biopsy. 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: •
Kidney Biopsy Source: Bethesda, MD: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 2001. 4 p. Contact: Available from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390 or (301) 654-4415. Fax (301) 634-0716. E-mail:
[email protected]. Website: http://www.niddk.nih.gov/health/kidney/nkudic.htm. PRICE: Full-text available
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online at no charge; single copy free; bulk orders available. NIH Publication number: 014763. Summary: A biopsy is diagnostic test that involves collecting small pieces of tissue, usually through a needle, for examination under a microscope. A kidney biopsy can help find a diagnosis and determine the best course of treatment. A kidney biopsy may be recommended for patients with hematuria (blood in the urine), proteinuria (protein in the urine), or impaired kidney function. This brochure describes the indications for kidney biopsies and the procedure itself. Topics include the pre-biopsy patient preparation, the test procedure itself, what to expect immediately after the biopsy, and getting the results. The brochure concludes with the contact information for two resource organizations, and a brief description of the activities of the National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC), a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 1 figure. •
Liver Biopsy: Diagnosing Liver Conditions Source: Yardley, PA: The StayWell Company: KRAMES Health and Safety Education. 2002. 2 p. Contact: StayWell Company: KRAMES Health and Safety Education. 780 Township Line Road, Yardley, PA 19067. (800) 333-3032. Fax: (866) 722-4377. E-mail:
[email protected]. Website: www.staywell.com. PRICE: Single copy free; $20.95 for 50. Item number: 911260. Summary: This brochure describes the use of liver biopsy to help assess the health of the liver. In a liver biopsy, a needle is inserted through the skin (percutaneous) and into the liver. A small sample of liver tissue is then removed and sent to a lab to be examined. The brochure discusses the indications for having a liver biopsy, the pre-procedure preparation, possible risks and complications, what to expect during the procedure, what to expect after the procedure (including how to know when to call the doctor), and getting the results. One sidebar includes an illustration of the liver and a brief description of its physiology. 4 figures.
•
Tissue Sampling and Analysis Source: Manchester, MA: American Society for Gastrointestinal Endoscopy. 1991. 4 p. Contact: Available from American Society for Gastrointestinal Endoscopy. 13 Elm Street, Manchester, MA 01944. (508) 526-8330. PRICE: Single copy free. ASGE Publication No. 1025. Summary: This brochure, one of a series of statements discussing the use of gastrointestinal procedures commonly performed by endoscopists, discusses tissue sampling and analysis. The brochure discusses tissue sampling, including biopsy, snare excision, cytology, and culture; techniques and devices; and tissue sampling and analysis in diagnosing problems of the esophagus, stomach, small intestine, and colon. Guidelines for the appropriate use of endoscopy are based on critical review of the available data and expert consensus. 30 references.
•
Biopsy Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p.
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Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail:
[email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have various medical conditions with information on the use of a biopsy to diagnose the condition. Types of biopsies include excisional and incisional biopsies, a shave biopsy, a punch biopsy, and fine needle aspiration. Once the specimen is removed, it is processed into thin, stained slices mounted on a glass slide. Frozen sections can provide a quicker diagnosis; however, their quality is not nearly as good as is found in regular slides. A report on the specimen has three main parts: the gross description, the microscopic examination, and the diagnosis. •
Punch Biopsy of the Skin Source: American Family Physician. 65(6): 1167-1168. March 15, 2002. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail:
[email protected]. Website: www.aafp.org. Summary: This journal article uses a question and answer format to provide people who may need to undergo punch biopsy with information on this procedure. The article explains what punch biopsy is and how it is performed, what happens to the biopsy specimen once it is removed, what complications may occur following punch biopsy, what happens to the site where the piece of skin was removed, and how long before results are available. In addition, the article provides skin care guidelines following punch biopsy.
•
Liver Biopsy Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse (NDDIC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. 2000. 2 p. Contact: Available from National Digestive Diseases Information Clearinghouse (NDDIC). 2 Information Way, Bethesda, MD 20892-3570. (800) 891-5389 or (301) 6543810. Fax (301) 634-0716. E-mail:
[email protected]. Website: www.niddk.nih.gov. PRICE: Full-text available online at no charge; single copy free; bulk copies available. Summary: With a liver biopsy, the physician is able to examine a small piece of tissue from the liver for signs of damage or disease. This fact sheet reviews the technique of liver biopsy. Designed for patients who will be undergoing a liver biopsy, the fact sheet reviews preparation, the procedure itself, and what to expect during the recovery time. The physician decides to do a liver biopsy after tests suggest that the liver is not working properly. Liver biopsy is considered minor surgery and is done at the hospital; the entire procedure takes about 20 minutes. The fact sheet describes standard liver biopsy, laparoscopic biopsy, and transvenous (through the vein) biopsy. After biopsy, the physician will put a bandage over the incision and have the patient lie on their right side, for at least 2 hours. The patient may remain in the hospital for up to 24 hours after the surgery to recover from the sedative and to allow the medical staff to check for complications before sending the patient home. The fact sheet notes that like any surgery, liver biopsy does have some risks, such as puncture of the lung or gallbladder,
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infection, bleeding, and pain, but these complications are rare. One diagram illustrates the anatomical location of the liver in relation to other organs in the abdomen. 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 “biopsy” (or synonyms). The following was recently posted: •
ACR Appropriateness Criteriatm for needle biopsy in the thorax Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2498&nbr=1724&a mp;string=biopsies 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 biopsy. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to biopsy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with biopsy. 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 biopsy. 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 “biopsy” (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 “biopsy”. 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 “biopsy” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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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 “biopsy” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
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
21
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)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
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
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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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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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
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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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
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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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/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
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 biopsy: •
Basic Guidelines for Biopsy Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Biopsy - biliary tract Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003894.htm Biopsy - polyps Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003415.htm
•
Signs & Symptoms for Biopsy Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm
•
Diagnostics and Tests for Biopsy Abdominal wall fat pad biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003841.htm
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Adrenal biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003900.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Biopsy - polyps Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003415.htm Biopsy of the biliary tract Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003894.htm Bladder biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003902.htm Bone lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003923.htm Bone marrow biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003934.htm Breast biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003920.htm Bronchoscopy with transtracheal biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003859.htm Carpal tunnel biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003925.htm Cervical biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003912.htm Chorionic villus biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003406.htm Cold cone biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003910.htm Colonoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003886.htm Colposcopy-directed biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003913.htm Cysts Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003240.htm EGD (esophagogastroduodenoscopy) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003888.htm
Online Glossaries 255
Endometrial biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003917.htm Endoscopic retrograde cholangiopancreatography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003893.htm Endoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003338.htm ERCP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003893.htm Gum biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003852.htm Liver biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003895.htm Lung needle biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003860.htm Lymph node biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003933.htm Mediastinoscopy with biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003864.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Muscle biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003924.htm Myocardial biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003873.htm Nasal mucosal biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003848.htm Nerve biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003928.htm Open lung biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003861.htm Open pleural biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003863.htm Oropharynx lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003850.htm
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Parathyroid biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003898.htm Pleural needle biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003862.htm Rectal biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003891.htm Renal biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003907.htm Salivary gland biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003847.htm Skin lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Skinny-needle biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003899.htm Small bowel biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003889.htm Synovial biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003922.htm Testicular biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003908.htm Thyroid excisional biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003901.htm Tongue biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003849.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm Upper airway biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003856.htm Ureteral retrograde brush biopsy cytology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003906.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •
Background Topics for Biopsy Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm
Online Glossaries 257
Aspiration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002216.htm Benign Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002236.htm Bile Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002237.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Cervix Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002317.htm Duodenum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002347.htm Hepatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002378.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Malignancy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002253.htm Pedicle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002285.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm Vagina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002342.htm
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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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BIOPSY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [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] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acoustic: Having to do with sound or hearing. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH]
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Acute tubular: A severe form of acute renal failure that develops in people with severe illnesses like infections or with low blood pressure. Patients may need dialysis. Kidney function often improves if the underlying disease is successfully treated. [NIH] Acyl: Chemical signal used by bacteria to communicate. [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] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] 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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adnexa: The appendages of the eye, as the lacrimal apparatus, the eyelids, and the extraocular muscles. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems
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that can improve cardiorespiratory endurance. [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] 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]
Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Agraphia: A pathological lack or loss of the ability to write, usually resulting from a brain lesion. [NIH] Air Embolism: Occurs when the lungs over expand to the point that air bubbles are forced through the air sacs of the lungs into the circulatory system. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. [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] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH]
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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] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [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] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form
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proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] 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] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] 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 shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [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] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH]
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Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angioscopes: Endoscopes used for viewing the interior of blood vessels. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Angulation: Deviation from the normal long axis, as in a fractured bone healed out of line. [NIH]
Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Anoscopy: A test to look for fissures, fistulae, and hemorrhoids. The doctor uses a special instrument, called an anoscope, to look into the anus. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiosis: A property of microorganisms which enables one microorganism to kill, injure, or inhibit the growth of a different microorganism. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH]
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Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IgG whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. [NIH] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antifungals: Drugs that treat infections caused by fungi. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] 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
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associated with tumor growth. [NIH] Appendectomy: An operation to remove the appendix. [NIH] Approximate: Approximal [EU] 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] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] 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 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] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthroscopes: Endoscopes for visualizing the interior of a joint. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH]
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Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] 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] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Aural: Pertaining to or perceived by the ear, as an aural stimulus. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axilla: The underarm or armpit. [NIH]
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Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axillary dissection: Surgery to remove lymph nodes found in the armpit region. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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 Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium enema: A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [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] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta Rays: A stream of positive or negative electrons ejected with high energy from a
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disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [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] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH]
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Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood urea: A waste product in the blood that comes from the breakdown of food protein. The kidneys filter blood to remove urea. As kidney function decreases, the BUN level increases. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH]
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Body Regions: Anatomical areas of the body. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone marrow aspiration: The removal of a small sample of bone marrow (usually from the hip) through a needle for examination under a microscope. [NIH] Bone marrow biopsy: The removal of a sample of tissue from the bone marrow with a needle for examination under a microscope. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bowel Prep: The process used to clean the colon with enemas and a special drink. Used before surgery of the colon, colonoscopy, or barium x-ray. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Breast Implantation: Surgical insertion of an inert sac filled with silicone or other material to augment the female form cosmetically. [NIH] Breast-conserving surgery: An operation to remove the breast cancer but not the breast itself. Types of breast-conserving surgery include lumpectomy (removal of the lump), quadrantectomy (removal of one quarter of the breast), and segmental mastectomy (removal of the cancer as well as some of the breast tissue around the tumor and the lining over the chest muscles below the tumor). [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH]
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Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchoscope: A thin, lighted tube used to examine the inside of the trachea and bronchi, the air passages that lead into the lungs. [NIH] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadaver: A dead body, usually a human body. [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] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] 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] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]
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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]
Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] 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] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] 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]
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Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] 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] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] 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 gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] 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] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical intraepithelial neoplasia: CIN. A general term for the growth of abnormal cells on the surface of the cervix. Numbers from 1 to 3 may be used to describe how much of the cervix contains abnormal cells. [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] 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] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [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 wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chitin Synthase: An enzyme that converts UDP glucosamine into chitin and UDP. EC 2.4.1.16. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystectomy: Surgical removal 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] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]
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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] 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] Chondrosarcoma: A type of cancer that forms in cartilage. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic leukemia: A slowly progressing cancer of the blood-forming tissues. [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] 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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Circumcision: Excision of the prepuce or part of it. [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
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to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] 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] Claviceps: A genus of ascomycetous fungi, family Clavicipitaceae, order Hypocreales, parasitic on various grasses. The sclerotia contain several toxic alkaloids. Claviceps purpurea on rye causes ergotism. [NIH] Clavicle: A long bone of the shoulder girdle. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical 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] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup
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characteristics. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] 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 Polyps: Pedunculated or sessile growths arising from the mucous membrane of the colon. [NIH] Colonoscope: A thin, lighted tube used to examine the inside of the colon. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colposcope: A lighted magnifying instrument used for examination of the vagina and cervix. [NIH] Colposcopy: The examination, therapy or surgery of the cervix and vagina by means of a specially designed endoscope introduced vaginally. [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] Communicable disease: A disease that can be transmitted by contact between persons. [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
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'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cone biopsy: Surgery to remove a cone-shaped piece of tissue from the cervix and cervical
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canal. Cone biopsy may be used to diagnose or treat a cervical condition. Also called conization. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conization: The excision of a cone of tissue, especially of the cervix uteri. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [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] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [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] Core biopsy: The removal of a tissue sample with a needle for examination under a microscope. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH]
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Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]
Cryostat: A batchwise operating apparatus in which a cryogenic liquid or solid is used to maintain by evaporation a cryotemperature which needs not be constant but may vary in a predetermined fashion. [NIH] Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]
Cryptorchidism: A condition in which one or both testicles fail to move from the abdomen, where they develop before birth, into the scrotum. Cryptorchidism may increase the risk for development of testicular cancer. Also called undescended testicles. [NIH]
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Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] 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] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystectomy: Used for excision of the urinary bladder. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cystocele: Fallen bladder. When the bladder falls or sags from its normal position down to the pelvic floor, it can cause either urinary leakage or urinary retention. [NIH] Cystoscope: A thin, lighted instrument used to look inside the bladder and remove tissue samples or small tumors. [NIH] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with
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Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [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] Dacryocystorhinostomy: Surgical fistulization of the lacrimal sac for external drainage of an obstructed nasolacrimal duct. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] 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] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Dentists: Individuals licensed to practice dentistry. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU]
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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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Depth Perception: Perception of three-dimensionality. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Device Removal: Removal of an implanted therapeutic or prosthetic device. [NIH] Dexterity: Ability to move the hands easily and skillfully. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] 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, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH]
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Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during cryopreservation. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. [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] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] 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 roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diverticula: Plural form of diverticulum. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] 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] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH]
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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] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductal carcinoma in situ: DCIS. Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called intraductal carcinoma. [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] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]
Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Ectopic Pregnancy: The pregnancy occurring elsewhere than in the cavity of the uterus. [NIH]
Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles
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and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] 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] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] 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] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] 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] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enema: The injection of a liquid through the anus into the large bowel. [NIH] 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] Enhancer: Transcriptional element in the virus genome. [NIH] Eniluracil: An anticancer drug that increases the effectiveness of fluorouracil. Also called
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ethynyluracil. [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]
Enucleation: Removal of the nucleus from an eucaryiotic cell. [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] 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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi
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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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergometer: An instrument for measuring the force of muscular contraction. [NIH] Ergonomics: Study of the relationships between man and machines; adjusting the design of machines to the need and capacities of man; study of the effect of machines on man's behavior. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [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] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagogastroduodenoscopy: Exam of the upper digestive tract using an endoscope. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in
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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 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] Ethynyluracil: An anticancer drug that increases the effectiveness of fluorouracil. Also called eniluracil. [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] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excisional biopsy: A surgical procedure in which an entire lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]
Exocrine: Secreting outwardly, via a duct. [EU] 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] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at
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the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Membrane Oxygenation: Application of a life support system that circulates the blood through an oxygenating system, which may consist of a pump, a membrane oxygenator, and a heat exchanger. Examples of its use are to assist victims of smoke inhalation injury, respiratory failure, and cardiac failure. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extraocular: External to or outside of the eye. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [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
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development. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femoral Vein: The vein accompanying the femoral artery in the same sheath; it is a continuation of the popliteal vein and becomes the external iliac vein. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [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 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
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chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [NIH]
